2003; 5(2):89

INDIAN JOURNAL OF IJPP

PRACTICAL PEDIATRICS
A quarterly medical journal committed to practical pediatric problems and
management update presented in a readable manner
IJPP is a subscription Journal of the Indian Academy of Pediatrics
Indexed in Excerpta Medica dated since January 2003
Annual subscription:Rs. 300/- 10 years subscription:Rs.3000/-

Vol.5 No.2 APRIL-JUNE 2003

Dr. A. Balachandran Dr. D.Vijayasekaran
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 91
TOPIC OF INTEREST - LABORATORY MEDICINE
Editorial - Guidelines for collection of specimens for microbiological
investigations 93
- Elizabeth Mathai
Interpretation of laboratory investigations in the diagnosis of
intrauterine infections 99
- Indrashekar Rao
Diagnostic approach to the child with arthritis 105
- Ramanan AV, Akikusa JD
Rapid diagnostic tests - Benefits and Pitfalls 111
- Saranya N
Neonatal Metabolic screening tests 118
- Nair PMC
Laboratory diagnosis of persistent and chronic diarrhoea 125
- Shinjini Bhatnagar
Journal Office : Indian Journal of Practical Pediatrics, IAP - TNSC Flat, F Block, Ground Floor, Hall Towers,
56, Halls Road, Egmore, Chennai - 600 008. INDIA. Tel No.: 044-28190032 E.mail : ijpp_iap@rediff mail.com
Address for registered / insured / speed post / courier letters / parcels and communication by various
authors : Dr. A. Balachandran, Editor-in-Chief, Indian Journal of Practical Pediatrics, F Block, No. 177, Plot
No. 235, 4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.
1
Indian Journal of Practical Pediatrics 2003; 5(2):90

Laboratory evaluation of hypertension 133

- Vijayakumar M, Prahlad N, Nammalwar B.R.
Clinical Neurophysiology in Pediatric Practice 141
- Ayyar SSK, Suresh Kumar, Vasanthi D, Sangeetha V
NUTRITION
Smart nutrients and brain development 149
- Elizabeth K E
IJPP - IAP CME, 2001
Recognition of a critically ill child 154
- Ramachandran P
RADIOLOGIST TALKS TO YOU
Obstruction in urinary tract 159
- Vijayalakshmi G, Natarajan B, Ramalingam A
CASE STUDY
Dengue haemorrhagic fever in a boy with Bombay blood group -
A rare coincidence 163
- Janani Shankar, Adhisivam B
Caffeys disease (Infantile cortical hyperostosis) 165
- Mohammed Thamby, Nagarajan M, Ram Saravanan R
Neurofibromatosis type I with congenital pseudoarthrosis and
holoprosencephaly 167
- Preetha Prasannan, Veerendra Kumar, Jayakumar, Sukumaran TU
GLOBAL CONCERN
Severe acute respiratory syndrome (SARS) 170
PRACTITIONERS COLUMN
Tips for practising pediatrician 173
- Kamlesh R. Lala, Mrudula K.Lala
QUESTIONS AND ANSWERS 179
NEWS AND NOTES 92,98,104,132,140,153,158,180,182
FOR YOUR KIND ATTENTION
* The views expressed by the authors do not necessarily reflect those of the sponsor or
publisher. Although every care has been taken to ensure technical accuracy, no responsibility is
accepted for errors or omissions.
* The claims of the manufacturers and efficacy of the products advertised in the journal are the
responsibility of the advertiser. The journal does not own any responsibility for the guarantee of the
products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.
- Editorial Board
2

EDITORS DESK
We are pleased to bring out the issue on
Laboratory Medicine, which will be of immense
use to all our readers.
This issue was meticulously formulated by
Dr. S. Thangavelu, Asst. Professor, Pediatric
Intensive Care Unit (PICU), Institute of Child
Health and Hospital for Children, Chennai. He
has carefully chosen the topics which are relevant
to all the practising pediatricians, academicians
and postgraduates. We are thankful to him for
his sincere effort in bringing out this interesting
and informative issue.
The new strides in the day to day
developments in laboratory medicine need
periodic review by experts in the field.
The editorial by Dr. Elizabeth Mathai is very
informative for all those engaged in clinical
practice. She has given the guidelines for
collection of specimens for microbiological
investigations. We thank all the authors who have
contributed articles to this special issue in their
respective field of interest. They have shared their
Published and owned by Dr. A. Balachandran, from Halls Towers, 56, Halls Road,
Egmore, Chennai - 600 008 and Printed by Mr. D. Ramanathan, at Alamu Printing Works,
9, Iyyah Mudali Street, Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.
3
2003; 5(2):91
rich knowledge and vast experience in their
articles for the benefit of our readers.
In the current scenario of increasing
consumer awareness about the laboratory
investigations, this issue will be of immense help
to the practicing pediatricians while ordering
investigations in the management of day to day
problems in clinical practice.
We have also included an article on Severe
Acute Respiratory Syndrome (SARS) for the
benefit of our readers to highlight the salient
features of the recent outbreak of this disease.
The third and fourth issue of IJPP for this
year will be on Infectious diseases and HIV
infection respectively.
We welcome the comments and suggestions
from the members for further betterment of the
journal. We also invite you to share the problems
faced in clinical management by practising
pediatricians. This will be discussed by experts
in the journal.
Indian Journal of Practical Pediatrics 2003; 5(2):92

NEWS & NOTES

INFANT AND YOUNG CHILD NUTRITION CONFERENCE
Theme: Men in Child nutrition and Care
Organised by
IAP Tamilnadu State Chapter, IAP-Chennai City Branch,
Breastfeeding Promotion Network of India & Nutrition Society of India
Date : 13th July, 2003
Venue : Hotel Vijay Park, 12 Jawahar Lal Nehru Salai, Inner Ring Road,
Arumbakkam, Chennai 600 106. Ph. No. 23791314
Near Hotel Radha Park Inn
Delegate Fee: Rs.300/- PG Student: Rs.250/-
Preconference Lactation Management Course : Date: 12th July, 2003
Venue: ICH & HC and M.H., Egmore, Chennai 600 008.
Registration Fee: Rs.200/- (Limited to 40 delegates only)
Last Date for registration: 5th July, 2003
Cheque / DD should be drawn in favour of CHEN NUTRICON 2003.
For outstation cheque please add Rs.50/-.
For registration contact
Dr.D.Gunasingh
Organising Secretary, Infant and Young Child Nutrition Conference
IAP Flat, F block, Halls Tower, 56 (Old No33), Halls Road, Egmore, Chennai 600 008.
Ph. No.044-28191524 Email: iaptnsc@vsnl.net

1ST NATIONAL CME ON INFECTIOUS DISEASES IN CHILDREN:

FROM PROBLEMS TO SOLUTION
Organised by : IAP Infectious Diseases Chapter
Venue: Asutosh Birth Centenary Hall: Indian Museum, Kolkata,
Date: 17th, 18th May 2003
Registration Fee Upto 28.02.2003 Upto 30.04.2003 Spot
Delegate Rs.500/- Rs.600/- Rs.750/-
Postgraduate Rs.400/- Rs.500/- Rs.600/-
DD or Cheque to be drawn in favour of IAP INFECTIOUS DISEASES CHAPTER
payable at Kolkata. Rs.50/- to be paid extra for outstation cheque. No cheque will be accepted
after 15.04.2003
Address for correspondance: Dr.Tapan Kr. Ghosh, Organising Chairperson, National CME
on Infectious Diseases in Children, 13, Neogi Pukur Bye Lane, Kolkata 7000 014. Ph: 033-22445551/
22164351, Mobile: 9831179718. Email: dr_tkghosh@rediffmail.com

4

EDITORIAL
GUIDELINES FOR
COLLECTING SPECIMENS
FOR MICROBIOLOGICAL
INVESTIGATIONS
The most important factor that determines
the accuracy of any report is the quality of the
sample received for testing. A wrong sample can
not only miss the pathogen but also lead to wrong
therapy. For example, a badly collected sputum
sample can lead to identification of members of
commensal flora as pathogens resulting in wrong
choice of antibiotics. Therefore, it is important
that all individuals involved in patient care should
understand the critical nature of maintaining
specimen quality.
Diagnostic tests offered by microbiology
laboratories include cultures to isolate the
pathogen, immunological tests to detect antibody
response or antigens and more recently,
molecular techniques to detect nucleic acids of
the suspected pathogen. In India, however,
laboratories mostly offer bacterial and fungal
cultures and serology only. Therefore some
important guidelines for collecting specimens for
these investigations are presented.
The sample received in the laboratory should
ideally have the original numbers and proportions
(or close to it) of bacteria as in the infected site,
in a viable state. In order to achieve this, one has
to choose the appropriate anatomical site for
sampling, collect and transport the sample
properly. It is helpful to remember the following
general principles in this regard.
1. The sample has to be appropriate and
representative. Collect samples from the site
5
2003; 5(2):93
where the pathogen is most likely to be found
(usually the infected site) and at a stage when
organisms may be found in maximum numbers.
(S.typhi is most likely isolated from blood during
the first week of illness).
2. Care must be taken to send adequate quantity
of specimen as adequate material is required for
making smears and performing cultures on
multiple media. If different types of cultures
(e.g., fungal, anaerobic, mycobacterial) are
required, additional material should be sent.
3. Collect samples taking care to avoid/minimize
contamination with normal flora. In certain
situations like, swabs from burn wounds,
decubitus ulcer, etc it is impossible to avoid
contamination with normal flora. In these cases,
care should be exercised in interpreting culture
reports. It is also advisable that items like Foleys
catheter tips, which are likely to contain a variety
of colonizing organisms, are not sent for culture.
4. Antibiotic therapy can make organisms
nonviable or decrease the numbers. Therefore,
collect samples for bacterial culture prior to
initiating antibiotic therapy. In limited conditions,
for example, infection with bacteria resistant to
the antibiotic being used or when there is lack of
penetration of antimicrobial to the site of
infection, bacteria can still be isolated from
infected sites. While interpreting culture results
take this information into consideration.
5. For culture, always use sterile leak proof
containers that can be closed tightly. Do not fill
to the brim and always avoid soiling of the
exterior with sample while collecting and
transporting. Avoid soaking swabs in saline/
distilled water prior to specimen collection.
Indian Journal of Practical Pediatrics
6. Label the container clearly with patient
identification details and send the sample to the
laboratory along with the request slip detailing
the nature of infection, type of sample, time of
collection and any other pertinent information.
Adequate clinical information will help the
microbiologist to assess the sample and modify
processing for special needs.
7. All samples are to be considered potentially
infective. It is therefore mandatory that
appropriate precautions are taken like wearing
of gloves and mask are taken while handling
samples.
8. In general, transport without delay and without
additives.
1. Urinary tract infection (UTI)
UTI is diagnosed by demonstrating infected
urine in the bladder. The most reliable method
of achieving this is by culture of a representative
sample of urine.
To avoid contamination with perineal and
urethral flora, midstream clean catch urine is
collected directly into a wide mouth sterile
container. Since this is a specimen collected by
the patient, clear instructions should be given
regarding method of collection; children need to
be supervised when samples are collected. In
babies and children who cannot co-operate, urine
may be collected by suprapubic aspiration. Urine
may be collected by aspiration from long term
indwelling catheters after cleaning the site of
aspiration with disinfectant. Catheter tips are not
good samples for diagnosing UTI and should be
avoided.
Urine for culture should reach the lab within
two hours. If this cannot be achieved, urine can
be refrigerated up to a maximum of 4 to 6 hours.
Urine for dark field microscopy for lepto-
spirosis should be collected before antimicrobial
6
2003; 5(2):94
therapy and transported immediately to the
laboratory, to visualise motile spirochaetes.
2. Pyogenic infections like wound and burns
infection / ulcers / abscesses / cellulitis
The most appropriate specimen to diagnose
a pyogenic infection is aspirated pus or biopsy
of the infected tissue. Since this is not always
practical, swabs of the infected site are used.
Swabs however are not suitable for anaerobic
culture and culture for fungus.
Prior to swabbing do not apply antiseptics.
If there are crusts, these can be removed using
sterile distilled water or sterile saline. Be
absolutely sure that saline/distilled water is sterile.
Using two swabs collect adequate pus or exudate
by allowing sufficient contact by rolling the swab
over the infected site. If exudate is absent, rub
the floor and margins of the infected areas with
the swab. Do not wet swabs with saline/distilled
water.
If there is an abscess, aspirate the pus and
transfer into a sterile plain (no additives) tube
with tight fitting stopper. The column of pus
will also allow anaerobic conditions to be
maintained for a period of time. Biopsies should
be sent in sterile plain (no additives) container
as early as possible to the laboratory. If the tissue
is very small and liable to drying, transport in a
small amount of sterile (make absolutely sure)
saline.
Transport without delay. If delay is
inevitable the sample can be refrigerated for a
maximum period of 4 to 6 hours. Samples for
anaerobic culture should not be refrigerated.
3. Fluids
Fluids from normally sterile areas like the
CSF, ascitic fluid, pleural fluid, synovial fluid
etc should be sent in sterile containers. If they
are liable to clot, collect in containers with

anticoagulants such as 2.5% sodium citrate. Do
not submit swabs dipped in fluid for culture.
Do not refrigerate these samples since some
of the potential pathogens are temperature
sensitive.
4. Upper respiratory infection.
Collect respiratory samples taking care to
minimize contamination with normal flora.
Throat swab: Collect throat swab under proper
vision. Depress the tongue and make the patient
say a long ah. Using two swabs rub well over
tonsils, the tonsillar fossa on both sides and lastly
the posterior pharyngeal wall. In addition, collect
any obvious exudate. Withdraw the swabs
without touching tongue and cheek. Place the
swab in a sterile container without additives.
Drying of the swab will not affect the recovery
of beta haemolytic streptococci.
If membrane like lesions are present,
collect a bit and send for culture. It is extremely
important in this situation, to give the laboratory
the relevant clinical information.
Throat and nasopharyngeal swabs are not
useful for identifying the aetiogical agents of
sinusitis, or acute otitis media. Culture is not
required on a routine basis for these infections.
Treatment can be started empirically since most
infections are caused by a few limited pathogens.
For resistant sinusitis, sinus pus should be
cultured. To identify the cause of otitis, collect
fresh discharge (if present) under vision and after
cleaning the crusts away using sterile saline/
distilled water. If there is no discharge,
tympanocentesis may be required.
Nasal swabs are taken if a staphylococcal
carrier state is suspected. Nasopharyngeal
sampling requires special swabs and is indicated
mostly in detecting carrier states (e.g.
meningococci).
7
2003; 5(2):95
5. Acute lower respiratory infections (LRI)
The most frequently sent sample for the
diagnosis of LRI is sputum. However, the value
of sputum culture is limited by the inability to
avoid contamination with oral flora.
Rinse the mouth prior to collection, with
water, a few times. Encourage the patient to
cough deeply and collect the coughed out material
directly into a wide mouthed sterile bottle with
screw cap. Do not add saliva into this. Early
morning sample, collected during the first bout
of cough after waking up, is best for isolating
pathogens. For children, sputum collection should
be done under the supervision of a trained person.
Send the sample without delay and without
additives. Refrigeration can affect the recovery
of pathogens like H.influenzae
In the laboratory, sputum is assessed for
quality. A good quality specimen will have large
number of pus cells with very few squamous
epithelial cells.
Since the agents of bacterial pneumonia like
S. pneumoniae and H .influenzae can be normal
commensals in the upper respiratory tract, care
has to be taken while interpreting results. It should
also be remembered that bacterial respiratory
pathogens like Mycoplasma pneumoniae,
Chlamydiae pneumoniae and Legionella
pneumophila will not grow in routine sputum
culture and cannot be identified using Gram stain.
These infections are currently diagnosed using
non cultural methods like immuno-diagnosis and/
or PCR.
M.tuberculosis will also not grow in routine
culture and cannot be seen in Gram stain.
Therefore a special request should be made if
pulmonary tuberculosis is suspected.
Nosocomial pathogens are survivors and
will grow on routinely used media.
Indian Journal of Practical Pediatrics
Agents of pneumonia in an immuno-
compromised patient may be different from those
in a normal host. Therefore, this information
should be given to the laboratory and tests for
agents like P.carinii, requested separately if
indicated.
Broncho-alveolar lavage (BAL) collected
properly is a better sample than sputum. However
contamination with normal flora can not be ruled
out in this sample also.
6. Infections in the eye
Corneal ulcers require microbiological
investigation. Corneal scraping is the best sample
and it is advisable that this is done by an
ophthalmologist. Since the sample is extremely
small and organisms likely to be fastidious, the
sample is best inoculated at the site of collection
itself on to media for isolation - Blood agar and
Chocolate agar for bacteria; Sabourauds
dextrose agar for fungi. If acanthamoeba keratitis
is suspected, the medium for this culture also
should be included. Extra-material may be used
for microscopy. Sample both eyes separately.
7. Faeces
Culture is not required on a routine basis
for the management of diarrhea/dysentery.
If culture is indicated, collect the sample
directly into a sterile wide mouthed container with
screw cap or snap on cap. Samples mixed with
urine and water are not suitable.
Clean containers are sufficient for
parasitological examination.
8. Blood
Blood for culture should be drawn under
strict aseptic condition. Prepare the skin over the
vein as for a surgical procedure. Clean with 70%
alcohol and apply povidone iodine. Allow about
a minute for the iodine to act. Do not touch this
8
2003; 5(2):96
area again, without sterile gloves. Collect
adequate quantity of blood using a sterile dry
syringe and inoculate directly into blood culture
media, using the same needle. Several
commercial media are now available for blood
culture. Additional media may be needed for
fungal and mycobacterial culture. Blood to
medium ratio can range from1:10 to 1:5.
Warm the media to room temperature prior
to inoculation. Do not refrigerate after
inoculation. Multiple blood cultures may be
required for the diagnosis of endocarditis.
Bone marrow cultures may yield better
results in situations like typhoid fever and
brucellosis. These may be sent to the laboratory
or directly inoculated into blood culture medium.
Specimens for Mycobacteria smear and
culture
Collect specimens from the site of infection
as for routine culture.
Sputum is the recommended sample for
diagnosing pulmonary tuberculosis. Since the
sensitivity of sputum examination is low, the test
has to be repeated at least three times. An
alternative to sputum is fasting gastric juice,
aspirated early in the morning. The entire amount
should be sent in a sterile container within 30
minutes. Delay can make the organisms non-
viable.
Likelihood of a positive report from fluids
increase with the quantity sampled. Therefore
send as much as possible in sterile containers, to
enable the laboratory to concentrate the material.
For renal tuberculosis, send the entire early
morning collection of urine.
Specimens for anaerobic culture
Anaerobes can become nonviable even
within 30 minutes, when exposed to atmospheric

oxygen. Therefore samples collected without
additives should reach the laboratory within this
period.
Aspirated pus and biopsies are ideal for
anaerobic culture. Blood for anaerobic culture
should be inoculated directly into appropriate
media. Specimens collected using swabs and
sputum give unreliable results on anaerobic
culture and should not be sent.
Specimens for fungal culture
Culture is most often done to diagnose
subcutaneous, systemic and opportunistic fungal
infections. Biopsy of the affected site is the most
reliable specimen. Swabs are not suitable. Do
not refrigerate the samples, as some fungi are
temperature sensitive. If there are discharging
sinuses, collect and send any granules seen on
the gauze dressing.
CSF should be tested for diagnosing
Cryptococcal meningitis. This should be sent in
sterile containers, clearly mentioning the
suspected diagnosis.
For suspected pulmonary fungal infections,
BAL may be sent. However, results should be
interpreted carefully. Candida spp grown from
sputum and even BAL are most likely from oral
or oesophageal candidiasis. Similarly,
Aspergillus spp could be environmental
contaminants. Therefore, always correlate culture
report with clinical features; send another sample
- which should also yield the same fungus, and
request for a microscopy report of original
sample. In true infections the organism will be
seen almost always on microscopy of the sample.
To diagnose P.carinii infection, coughed out
sputum is not suitable. Induced sputum after
saline nebulisation can be used. Better still are
BAL and lung biopsy.
9
2003; 5(2):97
Blood for Serology
Serum is most commonly used for antibody
tests. Collect about 5ml blood (more if several
tests are required) using a dry syringe and transfer
into a clean dry test tube without anticoagulants.
Remove the needle before expelling blood into
the tube. If serum should be transported or stored
for a few days, use sterile tubes. To prevent serum
from being chylous, collect blood prior to food
intake or only after 4 hours following food.
For most antibody detection tests, blood can
be refrigerated for a day if delay is unavoidable.
Blood collected for cold agglutination test should
not be refrigerated prior to serum separation as
antibodies can attach to erythrocytes in the cold.
After separation, serum can be refrigerated
for a few days and frozen for a few months,
without loss in antibodies.
For functional assays like complement
assay, serum should be sent immediately to the
laboratory (to be received within 30 minutes) as
complement components are heat labile.
Antigen detection tests
Most of these are commercial tests.
Manufacturers instructions should be followed
for specimen collection and transport. In general,
collect the specimen from the site of infection. .
Elizabeth Mathai
Professor, Department of Microbiology,
Christian Medical College, Vellore, Tamilnadu
Further reading
1. Guidelines for collection, transport, processing,
analysis and reporting of cultures from specific
specimen sources. In: Koneman EW, Allen SD,
Janda WM, Schreckenberger PC, Winn WC
(ed) Color atlas and text book of diagnostic
microbiology, Lippincott, Philadelphia 1997;
pp 121-170
Indian Journal of Practical Pediatrics
2. Miller JM, Holms HJ. Specimen collection,
transport and storage In: Murray PR, Baron EJ,
Pfaller MA, Tenover FC, Yolken RH (ed)
Manual of Clinical Microbiology 7th ed, Ameri-
can Soceity of Microbiology Press, Washing-
ton DC 1999; pp 33-63
2003; 5(2):98
3. Myers and Koshis manual of diagnostic pro-
cedures in medical microbiology and immu-
nology/serology, compiled by faculty of micro-
biology, Christian Medical College, Vellore,
2001

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10

LABORATORY MEDICINE
INTERPRETATION OF
LABORATORY INVESTIGATIONS
IN THE DIAGNOSIS OF
INTRAUTERINE INFECTIONS
* Indrashekar Rao
Introduction
Maternal infection acquired shortly before
conception or during gestation can adversely
affect pregnancy outcome either by non
specific effects of maternal illness or directly
through microbial invasion of fetus or neonate.
The organisms causing intrauterine
infections can be classified as :
Viral: Rubella, CMV, HSV, HIV, VZV,
Parvovirus , hepatitis, coxsackie
Protozoal : Toxoplasma, malaria
Spirochaetal : Treponema
Bacterial : Listeria monocytogenes
The mode of infection can be haematogenous
across placenta, ascending infection from
infected cervix or due to contact between
fetus and infected genitalia during parturition.
There is a possibility of intrauterine
infection in an infant if there is a known
exposure of mother to infectious agent or if
the infant is small for gestational age or there
is failure to thrive. The other manifestations
are petechiae, hepatosplenomegaly, congenital
malformations, thrombocytopenia and skin rash.
* Professor of Pediatrics
Institute of child health,
Niloufer hospital, Hyderabad [A.P.]
11
2003; 5(2):99
The interpretation of various investigations will
be dealt as follows
Viral Infections
1. Rubella: [German measles]
This human specific RNA virus is a member
of togavirus family causing mild self-limiting
infection in adults but has a devastating effect
on fetus. Infection can occur at any time during
pregnancy but early gestation infection is very
destructive. Congenital rubella syndrome
presents as cataract, IUGR, retinopathy,
microcephaly, meningoencephalitis, congenital
heart disease, splenomegaly, thrombocytopenic
purpura. With maternal infection in first 12
weeks, the rate of foetal infection is 81%. As
the gestational age advances the infection rate
drops. Risk for congenital defects is low if foetal
infection occurs beyond 20 weeks.
Prenatal diagnosis: It is mainly done by isolating
virus from amniotic fluid and by identification
of rubella specific IgM by percutaneous
umbilical blood sampling. These tests are
limited by sensitivity and specificity.
Postnatal diagnosis: Definitive diagnosis is by
virus isolation in pharyngeal washings, CSF,
conjunctiva and lens at autopsy. Rubella virus
RNA can be detected by PCR in clinical
specimens. Detection of rubella specific IgM in
neonatal or cord blood is also confirmatory. In
addition to the congenital defects, the persistent
rubella specific IgG with no decline as expected
from maternally acquired IgG points to the
diagnosis of congenital rubella syndrome. The
interpretation of ELISA for rubella specific
antibodies is as given in Table 1.
Indian Journal of Practical Pediatrics 2003; 5(2):100

Table 1. Interpretation of ELISA for rubella specific antibodies

Age of infant Test result Interpretation
0 - 3 Months IgM + Intrauterine infection
3 - 12 Months IgM + Probably intrauterine infection
IgG + although widespread early post-
natal infection cannot be ruled out
[Rubella IgM/IgG Negative < 0.9 U/ ml
Equivocal 0.91 - 1.1 U/ml
Positive > 1.1 U/ ml]
Persistence of rubella specific haemagglutination inhibition titres beyond the period
expected from that of passively transferred maternal antibodies

2. Cytomegalovirus Isolation of virus or demonstration of CMV

DNA by PCR from urine or saliva at birth or
Infection by members of herpes virus within 1 - 2 weeks indicates definitive diagnosis.
family is characterised by typical cytopathology When detected after 2 weeks it might have been
of infected cells like cellular enlargement with perinatally acquired. Shell viral cultures are
intranuclear and cytoplasmic inclusions . The used for better isolation.
rate of intrauterine transmission from primary
The determination of CMV antibody titres
maternal infection is 30-40 %. Approximately
has got limited use. (Table 2)
18% develop significant disease. In mothers
with recurrent infection the fetus and newborn Table 2. Interpretation of CMV anti-
rarely show clinical symptoms. Risk of body titres
transmission in relation to gestational age is
uncertain although infection during early Antibody Result Interpretation
gestation carries a higher risk of fetal disease.
IgM + VE unreliable for
Symptomatic CMV presents either as an diagnosis; low
acute fulminant infection with multisystem sensitivity
involvement like petechiae, purpura, hepato
IgG + VE can be maternally
splenomegaly and jaundice. A second insidious
acquired; on
presentation is with microcephaly, IUGR,
followup positive in
chorioretinitis, periventricular calcifications,
infected infants
mental retardation, hearing deficits, motor
abnormalities, visual disturbances etc. IgG - VE In both mother
Prenatal diagnosis and fetus excludes
congenital infection
Amniocentesis and cordocentesis to detect
CMV DNA by PCR. CMV IgG/IgM antibodies
Postnatal diagnosis Negative : < 0. 91 U / ml
Infant presents with the characteristic Equivocal : 0.91-1.1 U / ml
symptoms. Positive : >1.1 U / ml ]

12

3. Herpes simplex virus
There are 2 distinct types and type 2 is
an important cause of neonatal disease.
Intrapartum transmission is the most common
mode of transmission and is associated with
active shedding from cervix and vagina . Intra
uterine infection is rare. Diagnosis is by high
degree of clinical suspicion . An infant presents
with the disease as vesicles on 6 th 9 th day
over skin , eye and mucocutaneous membranes.
One third of affected children present with
encephalitis and another one third with
disseminated infection with seizures, shock and
DIC / hepatitis .
IgM serology is of little use as it may not
reach diagnostic levels upto 3 weeks.
Virus isolation from lesions of oro and
nasopharynx .
In encephalitis identification of viral DNA
in CSF by PCR , increased CSF protein
levels and pleocytosis .
4. Human immunodeficiency virus
HIV is a cytopathic RNA retro virus
which enters the host CD 4 cell and destroys
the host immune system. Inutero and
intrapartum transmission from infected mother
accounts for 90 % of paediatric cases.
Transmission can occur throughout gestation
and HIV has been isloated from cord blood
and products of conception as early as 14
20 weeks of gestation .
Diagnosis: In the early neonatal period is
difficult as HIV specific IgG antibody is
passively transferred. The median age of
clearance is 13 months.
Positive IgG in a child less than 18
months indicates maternal infection but
cannot diagnose fetal infection .
13
2003; 5(2):101
Virus co-culture, p 24 antigen detection ,
HIV specific IgM / IgA all three have
low sensitivity in 1st week of life .
Early diagnosis of HIV DNA is by
PCR assay, positive predictive value in
neonates is 56% and older infants is
83%.
Interpretation of PCR assay
Age Result Interpretation
At birth 30 50 % + ve Intrauterine infection
7 days -ve at birth Intrapartum
but + ve transmission
at 7 days
False positive PCR : contamination with
maternal blood
Child exposed to HIV should be tested
at 1, 2 , 4 months by viral culture and
PCR. If negative at 4 months there is a
> 95 % assurance that infant is not infected.
Exposed infant is considered negative of
there are
- no physical finding of infection
- virological tests are - ve
- immunological tests - CD 4 counts
are normal
- > 12 months of age and two or more
HIV antibody tests are negative .
5. Varicella zoster virus
It is a member of herpes virus family.
Intrauterine transmission occurs but prior to
peripartum period no obvious clinical
impairment is seen. Congenital varicella
syndrome following maternal infection in first
trimester is 2 %
Prenatal diagnosis: By sonographic
abnormalities like hypoplastic extremities,
Indian Journal of Practical Pediatrics 2003; 5(2):102

clubfoot, flexed limbs, ventriculomegaly, rate in mothers with high viral loads.
porencephalic cyst, polyhydramnios, ascites, Coinfection with HIV increases transmission.
hydrops and calcification of lungs and
myocardium . Diagnosis

VZV specific IgM in fetal blood is Children born to HCV infected women
nonspecific screened at 6 12 months by PCR assay of
HCV RNA
VZV DNA detection by PCR in amniotic
fluid is specific Age Test result Interpretation
[HCV/RNA by PCR]
At birth: Virus isolation from vesicular fluid
on culture. Demonstration of four fold rise in 0-6 mo + ve can be due to
VZV antibody titre by fluorescent antibody to maternal antibody
membrane antigen.
6 -12 +ve Reliable of fetal
6. Parvo virus infection
These are small unenveloped viruses, most b. Hepatitis B
infectious strain is B19 whose overall rate of
transmission from an infected mother to fetus Intrauterine transmission is rare.
is 33%. Risk of fetal loss is 10 % . It has been Detection is by HBsAg specific IgG in serum
firmly linked to nonimmune fetal hydrops by
SPIROCHETAL INFECTIONS
affecting the haematopoietic cell lines. If acute
or recent parvovirus B 19 infection is Syphilis
confirmed in pregnant woman by positive
B19 specific IgM assay, serial ultrasonogram Syphilis can be transmitted to the infant
should be done for fetal hydrops or meconium regardless of duration of maternal disease but
peritonitis. more so in the first year of infection.
Transmission occurs more commonly after fourth
Prenatal diagnosis: Fetal blood and amniotic month of pregnancy. Liver is the primary site
fluid for parvovirus IgM specific antibody . of infection followed by secondary spread to
PCR to detect B 19 DNA . 100 % results skin, mucous membranes and bones.
when fetal blood is subjected to insitu Prenatal diagnosis: Amniocentesis and fetal
hybridisation . blood sampling to detect spirochaetes by:
Postnatal diagnosis: Serum IgM rises in 3
- dark field microscopy
days and falls by 2 3 months. Serum IgG
appears a few days after IgM disappears and - indirect immunoflourescent staining
lasts for years . - inoculation in rabbit
7. Hepatitis viruses Detection of DNA by PCR at 17 weeks of
a. Hepatitis C gestation is also diagnostic.
At birth: Dark field examination of
Single stranded RNA virus related to
mucocutaneous lesions.
flavivirus family. There is high transmission

14

If RPR and VDRL titres are fourfold
greater than maternal titres, fetal infection
is very likely
IgM fluorescent antibody is false positive
in 35 % due to interference by fetal IgM
directed against maternal IgG. This can
be minimised by separating both fractions.
Congenital neurosyphilis is difficult to
diagnose. CSF mononuclear pleocytosis,
increased protein, reactive CSF VDRL
may indicate infection.
PROTOZOAL INFECTIONS
1. Toxoplasmosis
An intracellular protozoan with 30-40 %
vertical transmission. Rate increases with
gestational age at which acute infection occurs
and appears to correlate well with increasing
placental blood flow and is 90 % at term. The
severity of fetal disease is inversely
proportional to gestational age. Primary
neurological disease presents with intracranial
calcifications, chorioretinitis and convulsions.
The generalised disease presents with
hepatosplenomegaly, lymphadenopathy
,jaundice and anemia.
Prenatal diagnosis
Serial USG to detect hydrops, ventricular
dilatation, cerebral or hepatic calcification
and ascites.
Amniocentesis to isolate organisms by
inoculation in mice or by tissue culture.
PCR analysis-B1 gene amplification of
amniotic fluid has 97 .4 % sensitivity
Postnatal diagnosis
Isolation of toxoplasma in infant blood
peaks in first week
Detecting antigen / DNA by PCR in body
fluids is diagnostic.
15
2003; 5(2):103
Levels of maternally acquired IgG drops
at the rate of 50% per month, if not so
active fetal infection is suspected.
In infants, less than 3 months of age
transformation of lymphocytes on exposure
to toxoplasma antigen is a sensitive test.
2. Malaria
It is an obligate intracellular protozoan of
genus plasmodium. Neonatal infection has been
recorded with all species. The placenta has been
involved in most women who acquire malaria
during pregnancy. It is not clear whether
transmission to infant is transplacental or from
direct contact with maternal blood during
parturition.
Most infants have onset of symptoms by
8 week of life with fever, anemia and
th
splenomegaly. About one third have jaundice.
Diagnosis
Maternal history of febrile illness can be
elicited in most cases. The diagnosis of
congenital malaria can be entertained in any
infant who presents with fever, anemia,
hepatosplenomegaly and born to mother who
resided in an endemic area .The parasite can
be identified in cord blood and peripheral blood
by thick and thin smear.
BACTERIAL INFECTIONS
Listeria monocytogenes
It is a nonsporulating, -haemolytic gram
+ ve organism. Transplacental transmission is
believed to be the most significant mechanism
for acquiring early onset disease although
ingestion of aspirated amniotic fluid before
delivery is possible. Infected neonates present
with sepsis and pneumonia. They manifest
with anorexia, lethargy, vomiting, respiratory
distress, apnea, cyanosis and petechial rash.
Indian Journal of Practical Pediatrics 2003; 5(2):104

Diagnosis repeat IgM concentration shows a fall in

Diagnosis is prompted by maternal history
of still birth and repeated abortions. Diagnosis
is by culture of blood , urine and CSF. Gram
staining shows gram variable organisms which
look like diphtheroids.
Conclusion
To conclude, the specific IgM concentration
in serum may be increased due to leakage of
maternal blood. Under these circumstances a
case of maternal transfusion but increased in
active infection . Due to recent advances direct
serological and DNA analysis of fetoplacental
unit is possible and it can be used to determine
whether infection has occurred or not. In rubella
it facilitates continuation of pregnancy, while in
toxoplasmosis it guides the choice of
antimicrobial, but has no role in evaluating HIV
as the proceedure itself can inoculate the fetus.

NEWS AND NOTES

5TH NATIONAL CONGRESS ON PEDIATRIC CRITICAL CARE

Annual conference of Critical Care subchapter of IAP is hosted by IAP, Surat branch, on October 10th,
11th & 12th, 2003 at Hotel Holiday Inn , Surat. Theme of the conference: Demystification of Critical Care.
CME: October 10th, 2003. Conference: October 11th & 12th, 2003 Pre-Conference workshop / course,
a) PALS - 8th & 9th October b) Basic Pediatric Critical Care Course - 8th & 9th October
c) Workshop A - Advanced Mechanical Ventilation + All about Equipments - 9th October
d) Workshop B - Peritoneal Dialysis + IV access + All about Equipments - 9th October
Registration Details:
A) Conference: Till 30.04.03 Till 30.06.03 Till 15.09.03 Spot
1. IAP Member 2000 2400 2800 3400
2. P. G. Student * 1600 2000 2400 2800
3. Non IAP Member 2200 2600 3000 3600
4. Associate Delegate 1250 1250 1500 1500
B)Workshop /Course Till 30.04.03 Till 30.06.03 Till 15.09.03
1 PALS 1200 1200 1200 No Spot
2 Basic Pediatric Critical
Care course 2000 2250 2500 No Spot
For PG Student * 1500 1750 2000 No Spot
3 Workshop A 500 650 800 No Spot
4 Workshop B 500 650 800 No Spot
Note:- 1. Conference registration includes CME & Banquet.
2. Except PALS, registration for the conference is a prerequisite for participating in the
workshops / basic course.
3. Limited participants to be taken for all the 4 workshops on 1st come 1st serve basis.
4. P.G. Students are required to attach certificate from the Head of the Department.
5. Registration not required for children below 12 years.
For children between age 5 & 12 years, lunch / dinner coupons available at reasonable rate.
Organizing secretary, Dr.Kamlesh H. Parekh, Amruta Hospital, Raj Complex , Near Vaishno Devi Temple,
Bhatar Road, Surat. 395001, Ph: 3240141, 3244979, 3237280; Fax: 0261-8313636,
E-Mail:amrutahosp6@hotmail.com

16

LABORATORY MEDICINE
DIAGNOSTIC APPROACH TO THE
CHILD WITH ARTHRITIS
* Ramanan AV
** Akikusa JD
INTRODUCTION
Children presenting with acute arthritis
represent a relatively common problem for the
practicing general paediatrician. A large
proportion will have underlying conditions that
are self limiting in nature and require no more
than symptomatic treatment for a short period of
time. The challenge in their acute assessment is
to identify those with conditions that require more
than just symptomatic therapy. This requires a
good knowledge of conditions commonly
associated with acute arthritis.
A small proportion of children will go on to
have chronic arthritis, the commonest cause of
which is Juvenile Idiopathic Arthritis (JIA). It is
important to understand that this is a diagnosis
of exclusion and that mimics need to be
considered before making it. This article will
review the basic clinical approach to the child
with acute and chronic arthritis, covering issues
of differential diagnosis and initial management.
The child with acute arthritis
Acute arthritis for practical purposes is any
arthritis present for less than 6 weeks. The
diagnostic approach to the child with acute
arthritis is outlined in Fig 1. It is important to
keep in mind that up to 61% of children
* Division of Paediatric Rheumatology
Hospital for Sick Children
Toronto, Canada
17
2003; 5(2):105
presenting with rheumatologic symptoms will
either not have an underlying rheumatologic
disease or will remain undiagnosed 1 . This
underscores the importance of keeping a wide
differential diagnosis in mind and of ensuring
follow-up until such a time as the diagnosis
becomes clearer or symptoms resolve.
Trauma as a cause of acute arthritis will
usually be obvious, however it is not uncommon
for a traumatic event to bring to attention a joint
that has actually been swollen for some time.
Clues to the presence of an underlying more
chronic condition are wasting of the muscles of
the ipsilateral limb, joint contracture, and in the
lower limb (if present for long enough) leg length
discrepancy with the ipsilateral side being longer.
Acute traumatic injury as a cause of joint swelling
should be diagnosed with caution if the traumatic
event was not immediately followed by difficulty
in ambulation or refusal to weight bear. Acute
painful swelling of lower limb joints in response
to minor injury in young boys may also be the
first sign of an inherited bleeding disorder.
Septic joints are usually extremely painful
and held in a fixed position. In the case of the
hip, this is in flexion, abduction and external
rotation. The child will usually be febrile and on
laboratory testing will have evidence of raised
inflammatory markers (Erythrocyte
Sedimentation Rate/ C-reactive protein/
leukocyte count). It is important to note that acute
arthritis involving the hip joint as an initial
manifestation of JIA is extremely uncommon and
such a presentation mandates consideration of
more common differentials including septic
arthritis, slipped capital femoral epiphysis,
transient synovitis and Perthes disease. In the
Indian Journal of Practical Pediatrics 2003; 5(2):106

Traumatic injury of intracapsular structure:

SWOLLEN JOINT
Uncommon in the very young child
Diagnose with caution if the acute event is not painful enough
to prevent activity immediately
History of injury? Yes
Acute Joint Bleed (esp. if young):
May be first manifestation of haemophillia in the young child.
No
Pain and swelling following minor trauma
Significant Pain and Fever? Yes Septic Arthritis:
Joint extremely irritable- often held fixed.
No
Reactive/ Post Infective:
Recent Usually a monoarthritis of a large joint.
Acute Diarrhoea? Yes If polyarticular and migratory consider Rheumatic fever
Viral illness? Typical viruses Parvoviruses/Rubella/EBV/Mumps
Tonsillitis? Typical gut agents: Salmonella/Shigella/Campylobacter
Onset 7-14 days after acute illness
No Associated conjunctivitis/sterile urethritis suggest Reiters
History of syndrome. Fever may be absent
Inflammatory bowel IBD associated arthritis:
disease or chronic bloody Yes Usually a monoarthritis of large joints
diarrhoea? Peripheral arthritis usually reflects activity of bowel disease
No
Vasculitis:
Rash?
Commonest Henoch-Schonlein purpura.
(Palpable or on extensor Yes
Often very painful. Typically resolves quickly even without
surfaces)
treatment
No
Serum Sickness:
Recent Drug ingestion? Yes
Often associated with an urticarial rash
No Malignancy (e.g. Leukaemia/ Neuroblastoma):
Bone Pain? May present with true joint swelling pain
Lymphadenopathy? Yes Often constitutional symptoms e.g. fever/lethargy/pallor
Hepatosplenomegaly?
Juvenile Idiopathic Arthritis:
No
Peak age 1-5yr
Pain often surprisingly little compared other causes
Present > 6 weeks?
May affect any joint and multiple joints
Morning irritability/stiffness? Yes
Rarely presents in the hips as a first manifestation
Gradual refusal to
Unusual Infective Organism:
participate in usual activities?
Consider TB particularly if monoarthritis and from endemic
No area
1) Symptomatic treatment with NSAIDs
No Clear Diagnosis Yes
2) Organize on-going review
Adapted with permission from the Arthritis guideline of the Royal Childrens Hospital, Melbourne, Australia.
(http://www.rch.org.au/clinicalguide/pages/joint_acute.php)

Fig 1: Algorithm for approach to child with acute arthritis.

18

Table 1: Differential diagnosis chronic
arthritis in children*
Juvenile idiopathic arthritis
Connective tissue disorders
- systemic lupus erythematosus (SLE)
- juvenile dermatomyositis (JDM)
- mixed connective tissue disease (MCTD)
- scleroderma
- systemic vasculitis
Childhood sarcoidosis
Inflammatory bowel disease associated
arthritis
Other synovial conditions
- pigmented villonodular synovitis
- foreign body synovitis (plant thorn
synovitis)
- synovial hemangioma
- synovial chondromatosis
Infectious arthritis (including tuberculosis)
Reactive arthritis
Periodic fevers
Metabolic diseases
- mucopolysaccharidoses
- diabetes
- mucolipidoses
- hemochromatosis
* some of the causes of acute arthritis listed
in the algorithm could also lead on to chronic
arthritis
latter two conditions the child will not appear
toxic and the acute phase reactants should be
normal. Transient synovitis tends to be seen most
often in the 3-8 year age group, whereas Perthes
is more commonly seen in an older age group
(5-10yrs) and is more common in boys. Transient
synovitis is typically quite painful and may cause
the child significant difficulties in ambulation.
Perthes disease is classically described as a
painless limp. Slipped capital femoral epiphyses
tend to occur in the teenage age group, typically
older overweight boys, who present with pain and
limp.
19
2003; 5(2):107
Reactive arthritides are perhaps the most
common cause of acute arthritis in children.
Common agents are viruses such as Parvovirus,
Rubella and Epstein Barr virus. In endemic areas
hepatitis B should be borne in mind. Many of the
bacterial causes of gastroenteritis can be followed
by acute arthritis, usually of the large joints and
typically quite painful and associated with
elevated acute phase reactants on laboratory
testing. In such instances it is important to look
for joint sepsis, from which this form of arthritis
may be hard to distinguish, by arthrocentesis and
culture of synovial fluid. Streptococcal infection
may give rise to subsequent Rheumatic Fever or
Post Streptococcal Reactive arthritis2. Typically
the arthritis in both of these conditions involves
large joints, and in the case of rheumatic fever it
is migratory and very sensitive to non-steroidal
anti-inflammatory drugs (NSAIDs). Indeed
failure to respond to NSAID therapy within 48-
72 hours places the diagnosis in question. It is
important to remember that between 30% and
60% of patients with their first episode of acute
rheumatic fever will not have a history of
symptomatic pharyngeal infection 3, 4. Post
Streptococcal reactive arthritis tends to be more
persistent and not associated with other features
of acute rheumatic fever.
Both serum sickness5 (most often related to
drug ingestion) and vasculitis (the most common
being Henoch Scholein Purpura), may give rise
to a painful arthritis, typically of the large joints.
Associated features of these conditions will
usually be the clue to these diagnoses.
Perhaps the most worrying cause of acute
arthritis in children is malignancy, of which
leukaemia and neuroblastoma are the
commonest. While both may cause true acute
arthritis6, they more commonly cause bone pain,
which may be localized around joints and which
will frequently wake the child from sleep. The
pain associated with these conditions may be
Indian Journal of Practical Pediatrics
Table 2: ILAR classification criteria for juvenile idiopathic arthritis: Durban 1997
Systemic arthritis
Definition: Arthritis with, or preceded by, daily
fever of atleast 2 weeks duration that is docu-
mented to be quotidian for at least 3 days and
accompanied by one or more of the following:
1. Evanescent, non-fixed erythematous rash
2. Generalized lymph node enlargement
3. Hepatomegaly or splenomegaly
4. Serositis
Exclusions: None listed
Oligoarthritis
Definition: Arthritis affecting one to four
joints during the first 6 months of disease.
Two subcategories are recognized
1. Persistent oligoarthritis: affects no more
than four joints throughout the disease
course
2. Extended oligoarthritis: affects a cumulative
total of five joints or more after the first 6
months of disease
Exclusions:
a. Family history of psoriasis confirmed by a
dermatologist in atleast one first or second
degree relative
b. Family history consistent with medically
confirmed HLA B-27 associated disease in
atleast one first or second degree relative
c. Positive RF test
d. HLA B-27 positive male with onset of
arthritis after 8 years of age
e. Presence of systemic arthritis as defined
above
Polyarthritis (RF negative)
Definition: Arthritis affecting 5 or more joints
during the first 6 months of disease, associated
with negative RF tests on 2 occasions atleast 3
months apart.
Exclusions:
a. Presence of RF
b. Presence of systemic arthritis as defined
above
20
2003; 5(2):108
Polyarthritis (RF positive)
Definition: Arthritis affecting 5 or more joints
during the first 6 months of disease, associated
with positive RF tests on 2 occasions atleast 3
months apart.
Exclusion:
a. Absence of positive tests for RF on two
occasions atleast 3 months apart
b. Presence of systemic arthritis as defined
above
Psoriatic arthritis
Definition:
1. Arthritis and psoriasis or
2. Arthritis and at least two of the following
a) Dactylitis
b) Nail pitting or onycholysis
c) Family history of psoriasis confirmed by
dermatologist in at least one first degree
relative.
Exclusions:
1. Presence of rheumatoid factor
2. Presence of systemic arthritis as defined
above
Enthesitis related arthritis
Definition: Arthritis and enthesitis, or arthritis
or enthesitis with atleast two of the following:
1. Sacroiliac joint tenderness and/or inflamma
tory spinal pain
2. Presence of HLA-B27
3. Family history in atleast one first or second
degree relative of medically confirmed
HLA-B27 associated disease
4. Anterior uveitis that is usually associated
with pain, redness or photophobia
5. Onset of arthritis in a boy after the age of 8
years
Exclusions:
a. Psoriasis confirmed by a dermatologist in
atleast one first or second degree relative
b. Presence of systemic arthritis as defined
above

Other arthritis
Definition: Children with arthritis of unknown
cause that persists for atleast 6 weeks but that
either
1. Does not fulfill criteria for any of the
categories, or
2. Fulfills criteria for more than one of the
other categories
Exclusions:
Patients who meet criteria for other categories
extreme and may result in the child not weight
bearing. Under these circumstances it is crucial
that the child undergoes a thorough physical
examination of the lymphoreticular system and
at the very least a complete blood count taken.
Other investigations which may be required in
order to ensure that a malignancy is not being
missed are a bone marrow aspirate, urinary
catecholamines and CT or Ultrasound scan of the
abdomen.
Clearly some of the conditions associated
with acute arthritis discussed above require
specific therapy, but a great many require
symptomatic treatment only. If there is evidence
of true synovitis or joint effusion such treatment
should be with NSAIDs at appropriate doses
(Table 3). With this therapy the majority of these
conditions will settle within 6 weeks. If they do
not then consideration must be given to the causes
of chronic arthritis in children
The child with chronic arthritis
Chronic arthritis is defined as the persistence
of arthritis for 6 weeks or more. Common causes
of chronic arthritis are shown in Table 1. Of all
the causes of chronic arthritis in children JIA is
the most common.
Most connective tissue disorders including
lupus, juvenile dermatomyositis (JDM) and
scleroderma may have arthritis as one
manifestation. Approximately 90% of lupus
21
2003; 5(2):109
Table 3: Standard Anti-inflammatory
doses of NSAID
Naproxen 15-20mg/kg/d in 2 divided doses
Ibuprofen 30-40mg/kg/d in 3 divided doses
Indomethacin 2-3mg/kg/d in 3 divided doses
patients and 65% of JDM patients will have
arthritis/arthralgia during the course of their
illness7. A thorough clinical examination looking
for other features which might suggest these
diagnoses is essential. Such features include
Gottrons papules, heliotrope rash, proximal
muscle weakness, mucocutaneous changes,
alopecia and evidence of serositis.
Classic early onset childhood sarcoidosis is
characterized by a triad of arthritis, uveitis and
rash. The arthritis of childhood sarcoidosis is
characterized by boggy tenosynovitis with
relatively painless effusions and good range of
movement8.
Arthritis is the most common extra-intestinal
manifestation of inflammatory bowel disease.
There are two patterns of joint involvement:
peripheral and, less commonly, sacroiliac arthritis
(spondyloarthropathy). The peripheral arthritis
usually reflects the activity of the underlying
bowel disease, while, the sacroiliac arthritis tends
to follow an independent course9. Uncommonly,
the arthritis may precede the bowel
manifestations. In this situation the diagnosis is
suggested by the presence of abdominal
symptoms, occult blood in stools, low
haemoglobin, thrombocytosis, a low serum
albumin and a positive pANCA (anti-neutrophil
cytoplasmic antibody), the latter found in 60-80%
of cases.
The differential diagnosis of chronic
monoarthritis includes tuberculosis, in endemic
areas, and local disorders of synovium. An
example of the latter is pigmented villonodular
synovitis, a rare condition characterized by
Indian Journal of Practical Pediatrics
recurrent painless effusions which, on aspiration,
are heavily blood-stained. Both T 1 and T 2-
weighted MRI studies reveal hypertrophic
synovium, with very low signal density as a result
of hemosiderin deposition 10 . Synovial
hemangioma, most commonly seen in the knee,
usually presents as an intermittent hemarthrosis.
The diagnosis of JIA is a clinical one. The
use of investigations is primarily to exclude
differential diagnoses and, once the diagnosis is
made, to aid in classification and prognostication.
Perhaps the one exception is a slit-lamp
examination of the eye, which can be very helpful
in the diagnostic work-up of a child with arthritis.
A significant proportion of children with JIA
develop clinically silent but potentially blinding
chronic uveitis. On average, uveitis is seen in
15-20% of patients with pauciarticular and 5 %
of patients with polyarticular JIA11. The presence
of uveitis in a child presenting with arthritis
narrows the differential essentially to JIA and
sarcoidosis, of which the former is overwhel
mingly more common. The Inter national League
Against Rheumatism (ILAR) has classified JIA
into seven categories with inclusion and exclusion
criteria for each type (Table 2)12. It is important
to remember that these criteria were proposed
mainly to classify patients for research and
prognostic purposes, but as with many such
criteria, they also serve as a diagnostic tool.
Initial management of chronic arthritis: As
with acute arthritis the initial management of a
child presenting with chronic arthritis revolves
around symptomatic relief, which in most
instances will be an NSAID at anti-inflammatory
doses (Table 3). Ongoing management will
depend on the underlying diagnosis. Whatever
the cause, it is important to remember that patient/
parent education and physiotherapy are integral
to the successful management of many of the
conditions which result in chronic arthritis in
children.
22
2003; 5(2):110
References
1. Rosenberg AM. Analysis of a pediatric rheu-
matology clinic population. J Rheumatol 1990;
17:827-830.
2. Jansen TL, Janssen M, van Riel PL. Grand
rounds in rheumatology: acute rheumatic fe-
ver or post-streptococcal reactive arthritis: a
clinical problem revisited. Br J Rheumatol
1998; 37:335-340.
3. Veasy LG, Wiedmeier SE, Orsmond GS, et al.
Resurgence of acute rheumatic fever in the in-
termountain area of the United States. N Engl J
Med 1987; 316:421-427.
4. Lee LH, Ayoub E, Pichichero ME. Fewer
symptoms occur in same-serotype recurrent
streptococcal tonsillopharyngitis. Arch Otol
aryngol Head Neck Surg 2000; 126:1359-1362.
5. Kunnamo I, Kallio P, Pelkonen P, Viander M.
Serum-sickness-like disease is a common cause
of acute arthritis in children. Acta Paediatr
Scand 1986; 75:964-969.
6. Tuten HR, Gabos PG, Kumar SJ, Harter GD.
The limping child: a manifestation of acute leu-
kemia. J Pediatr Orthop 1998; 18:625-629.
7. Tse S, Lubelsky S, Gordon M, et al. The arthri-
tis of inflammatory childhood myositis syn-
dromes. J Rheumatol 2001; 28:192-197.
8. Shetty AK, Gedalia A. Sarcoidosis in children.
Curr Probl Pediatr 2000; 30:149-176.
9. Passo MH, Fitzgerald JF, Brandt KD. Arthritis
associated with inflammatory bowel disease in
children. Relationship of joint disease to activ-
ity and severity of bowel lesion. Dig Dis Sci
1986; 31:492-497.
10. Bravo SM, Winalski CS, Weissman BN. Pig-
mented villonodular synovitis. Radiol Clin
North Am 1996; 34:311-326.
11. Cassidy JT, Petty, R.E. Juvenile rheumatoid ar-
thritis. In: Cassidy JT, Petty RE, editors: Text-
book of Pediatric Rheumatology 2000:pp218-
321.
12. Petty RE, Southwood TR, Baum J, et al. Revi-
sion of the proposed classification criteria for
juvenile idiopathic arthritis: Durban, 1997. J
Rheumatol 1998; 25:1991-1994.
 2003; 5(2):111

LABORATORY MEDICINE

RAPID DIAGNOSTIC TESTS An ideal diagnostic tool needs to fulfill certain

BENEFITS AND PITFALLS requirements:

* Saranya N It should be easy to perform

The last decade has indeed been the decade Should not require expensive equipment
of diagnostics. To keep pace with the emergence Should not require electricity if possible, so
and re-emergence of several infections, it can be applied to field situations too
manufacturers have not left any stone unturned
Results obtained should be repeatable
in improving the quality of the available kits. In
addition, the need for faster and equally accurate, It should be highly sensitive and specific
reliable, sensitive and specific rapid kits has been It should aid in the diagnosis
felt more urgently. These rapid testing kits /
methods can be broadly divided into two In the pediatric age group in India, the
categories those that involve single step and infections commonly encountered are malaria,
depend on agglutination, flow-through and lateral typhoid, dengue, leptospirosis, tuberculosis and
flow etc. which take a few minutes and those that Hepatitis A. Several other viral and bacterial
involve multiple steps like ELISA, Passive infections are encountered too, though much less
Haemagglutination (PHA) and Molecular tools, frequently. The rapid tools available for these
which may take upto a few hours. infections will be dealt with, in reference to their
benefits and pitfalls.
Rapid testing devices
Typhoid
A major problem worldwide and is
Single step Multiple steps particularly rampant in the developing nations.
Early detection is vital for its control. With the
more recent blood culture techniques available,
it is possible to isolate, identify and give a
Agglutination ELISA Molecular complete blood culture report within four days.
Chromatography PHA PCR Some of the commercially available blood culture
WB DNA etc. media have an incorporated resin, which absorbs
(western the antibiotic that the patient might have been
blot) treated with. Hence the drawback of false
negatives in blood culture as a result of antibiotic
Flow-through Lateral flow usage in the patient has been removed. Table I
lists the merits and demerits of the available
* Director, diagnostic tests.
Lister Laboratory and Research Centre
Chennai 34.

23
Indian Journal of Practical Pediatrics
Table 1. Properties of diagnostic tests used in typhoid fever
Properties Culture (Ag) PCR (Ag)
Quality Gold standard Promising
(single)
Utility First week Early
Sensitivity 45 70% 72%
Specificity 100% 100%
(dead bacilli)
Result 4 days 1 2 days
Cost Moderately Expensive
expensive
* Negative Predictive Value
Rapid tests for typhoid are based either on
the principles of EIA (IgM and IgG antibody),
immuno-chromatography (antigen detection) or
agglutination. A positive test result even if
antigen is present, needs ideally to be
confirmed with a more specific test, while a
negative result does not preclude the presence
of infection. When an IgG test alone is positive,
a positive blood culture done a few days later
will resolve the issue of re-infection or relapse.
Detection of S. typhi infection using labelled
probes is 99% specific but a minimum of 500
organisms per ml is required while with PCR it
is 10/ml and with nested PCR 1-5 organisms per
ml is sufficient to detect an infection1.
Widal test has outlived its usefulness and
more often than not a very ambiguous report is
obtained. The test is most often ordered as the
initial and often the only diagnostic tool in
patients with suspected typhoid and when the
result is negative, a diagnosis of typhoid is no
longer considered. This test gives numerous false
positives that have led to unnecessary and
ineffective medication.
Blood culture remains the gold standard and
when done with observation of all necessary
precautions such as time of sampling, aseptic
procedures, volume of blood drawn, maintenance
24
2003; 5(2):112
Widal (Ab) Rapid tests (Ab)
Not useful (single) Not useful
Second week 4 7 days
36% 95%
Non specific *High NPV 96.1%
Overnight 1 hour IgG
3 hours IgM
Inexpensive Moderately
expensive
of ratio between blood and media and so on, a
definitive diagnosis of typhoid can be reached
within a day.
Malaria
Clinical or syndromic diagnosis is often used
to identify and treat malaria in remote areas where
diagnostic facilities are not available. In addition,
symptoms of malaria are often non-specific and
result in mis-diagnosis. Four species of malaria
that commonly infect man are the Plasmodium
vivax, falciparum, malariae and ovale. Of these
the P.falciparum causes the most fulminant forms
of infection while P.vivax is the most frequently
seen in India. Diagnostic techniques include the
time honoured blood films both thick and thin,
the quantitative buffy coat technique (QBC) and
several immuno-chromatographic tests based on
the Dipstick format. These are based on the
principle of detection of plasmodial histidine rich
protein-2 (HRP-2) or parasite specific lactate
dehydrogenase (pLDH) that is present in
P.falciparum infections. These tests are now
being applied for other forms of malaria but the
results have not been encouraging2. Table II
compares the commonly used tests.
Positive results obtained in the IC test need
to be confirmed by a more specific test. Rapid
 2003; 5(2):113

Table 2. Properties of tests used in diagnosis of malaria

Properties Smear QBC IC (Dipstick)
Usefulness Gold standard Extremely sensitive Falciparum
Principle Routine staining Flourescein stain Immuno Chromatography (IC)
Parasitic forms All All Falciparum Antigen
Sensitivity Can be missed 100% 100%
Specificity 100% False positives False positives

tests are useful for screening and confirmation Dengue

especially when,
This infection caused by a member of the
a) there are very few forms or Flavivirus family is transmitted to humans
b) if an inexperienced person is doing the through the bite of the Aedes mosquito. Antibody
testing2. appears within 3-5 days and is detectable for
around 90 days3. There are several methods used
Other recent field players are Enzyme
for the diagnosis of Dengue. PCR is used to detect
immuno-assay (EIA) and Multiplex Polymerase
the presence of the viral nucleic acid but is fairly
Chain reaction (PCR). EIA has been developed
expensive. Serological detection of Dengue
and evaluated, including tests for Pf HRP-2
infections are based on the principles of
antigen. However they only detect falciparum
haemagglutination inhibition, ELISA (IgM, IgG
malaria hence their usefulness is limited. They
and IgM and G combined) and the more rapid
equal microscopy in sensitivity, but are
tests being the Dipstick enzyme immuno-assay
impractical and expensive to use in the field. If
(IgM or IgM and G) and immuno-
an EIA test that was able to detect all forms of
chromatography to detect IgG alone or IgM and
malaria was available, that would perhaps be
IgG combined. Paired serum sampling is ideal
more useful.
to make a diagnosis of dengue and
A multiplex PCR has been developed for differentiate between primary and secondary
all four species using the target 18S single infections. Certain disadvantages of any IgM
stranded rRNA and serum sporozoite stage DNA test for dengue are that3
sequences. The Royal Tropical Institute
1) IgM may be undetectable for upto 5 days
Amsterdam has developed a qualitative Nucleic
and so a sample drawn earlier than this
Acid Sequence Based Assay (NASBA) method
period may give a false negative result. A
for detection and semi-quantification of as few
repeat sample drawn a week later will help
as 50 parasites per milliliter of blood, which is
resolve this issue.
many times more sensitive than microscopy.
However they are expensive to make, difficult 2) False positives in other flavi-virus infections
to run and need sophisticated equipment.
3) False positives as a result of stimulation by
Rapid tests can be used as supplemental non-flavi viruses.
tests but can never replace microscopy in the 4) A positive result does not indicate an active
diagnosis of malaria. infection
25
Indian Journal of Practical Pediatrics 2003; 5(2):114

All the serological assays can be completed
within a working day with the microtitre ELISA
taking about three hours and the immuno-
chromatographic tests about 15 minutes. Studies
done at Singapore have found that the microtitre
format capture ELISA for detection of IgM and
IgG when used together was superior to the use
of IgM or IgG alone, and showed good
correlation (sensitivity 99%, specificity 96%)4
when compared to the haemagglutination
inhibition assay which is considered to be the
ideal serological test.
problems, it is the remaining 10%-15% of patients
in whom early and rapid diagnosis is even more
imperative. Like in malaria, symptoms are non-
specific and can mimic any viral infection hence
this infection is often under-reported.
Rapid diagnostic tests for leptospirosis can be
divided into two groups:
Those based on the presence of antigen
a) Dark field microscopy (DFM) and special
stains

In summary, there is no single perfect b) Molecular techniques like PCR, RAPD,

diagnostic test for dengue. While viral isolation hybridisation methods and PGE
gives the best chance of a definitive diagnosis, it
These are ideal tools for the early diagnosis
takes time and cannot be performed in all
of leptospirosis. Molecular techniques are
laboratories. Clinical judgement therefore is
extremely sensitive, very expensive and are not
very important particularly in dengue and
available for routine use. Microscopy has been a
simple laboratory tests like a platelet count or
severely under-utilised tool and while the risk of
haematocrit should be used to institute the
false positives does exist, if done by a trained
appropriate supportive treatment without any loss
microscopist it can be extremely specific6.
of vital time3.
Those based on antibody presence
Leptospirosis
a) IgM detection assays like ELISA and Dipstick
A geographically widespread spirochetal
infection caused by members of the genus b) Agglutination tests like the PSAT, MAT, IHA
Leptospira, this infection has assumed endemic
proportions in certain states namely Andamans, c)Immuno-blotting assays like the Dot Blot assay
Gujarat, Tamilnadu and Kerala. More than 230
A commercially available IgM ELISA kit
serovars have already been identified. The
has been evaluated against the gold standard of
organism is shed in the urine of the reservoir host
the MAT and found to have a sensitivity of
into the environment and man acquires the
100% 7. The IgM PK ELISA with 89.9%
infection when the organism enters through
sensitivity and 97.4% specificity and the
cracks in the skin and mucous membranes.
Leptotest-S with an 89.9% sensitivity and 94.8%
Anicteric presentations account for 90% of
specificity have been found to be ideal for early
human leptospirosis. Icteric and anicteric cases
diagnosis in most laboratories according to
follow a biphasic course. Weils syndrome can
another study8.
be caused by any serovar in its severe form. All
forms of leptospirosis begin the same way and at Pitfalls of antibody detection in leptospirosis:
the start of infection it is not possible to predict
the outcome5. While almost 85% to 90 % of a) Paired sampling done 10-14 days apart is a
infections clear spontaneously with no residual must to demonstrate a rise or fall in titre.

26

b) A single positive titre is of no significance
as raised IgM antibody levels are detectable even
a year after infection.
c) Prior treatment with antibiotics may delay,
blunt or supress antibody production.
IgM ELISA tests are able to detect antibody
presence on an average five to seven days after
onset of an infection, however while an initial
sample might be negative, a second sample taken
a week later might show a significant rise in titre.
A practical problem that clinicians face is
accessibility of the patient after the initial visit.
Hence the search continues for a test that can give
a conclusive diagnosis with a single sample.
The MAT test has until recently been
considered the cornerstone for leptospirosis
diagnosis, however, the focus of researchers the
world over is now shifting towards antigen based
molecular methods of detection. A simple,
inexpensive, molecular tool that does not require
skilled personnel and that can be used in any
resource poor setting would be ideal. Ironically
enough, most of diagnostic research in the field
of leptospirosis has been done by the western
world, where leptospirosis is not as large a
problem as in tropical countries where it is
endemic in some.
The MAT test is an excellent
epidemiological and research tool but is not
suitable as a rapid screening or diagnostic
test5.
Tuberculosis
Pulmonary TB is among the foremost killer
diseases in India. According to estimates of the
WHO, 90 million new active cases have been
identified worldwide of whom a third have
already died. With AIDS having assumed
gigantic proportions, the situations can only
worsen. Sputum culture remains the gold standard
27
2003; 5(2):115
for the diagnosis of TB. Cultures are 81%
sensitive and 98.5% specific for active disease.
However reporting takes anywhere between 10
days with some of the newer techniques to three
to four weeks with the more conventional
methods, and hence when an immediate diagnosis
is required, culture cannot be used. Rapid
indication of drug resistance is also possible by
using MTB specific mycobacteriophages to
reflect the presence of viable tubercle bacilli in
the presence or absence of rifampicin9. The need
for early, rapid diagnosis is essential for prompt
institution of treatment.
Rapid tests for TB can be divided into two main
groups:
Direct
a) Sputum smear microscopy
b) Continuous automated mycobacterial liquid
cultures (CAMLiC)
c) Molecular techniques
Indirect
a) Line immuno-chromatographic serological
assays (LISA)10
b) ELISA
The best method for diagnosing
pulmonary TB is the sputum smear. PCR is
indicated in smear positive individuals who have
not had treatment for longer than seven days.
While it takes 10000 organisms to produce a
positive smear, even a few are sufficient to give
a positive PCR report11. However, the PCR does
not differentiate between dead and live bacilli and
hence a PCR report should be interpreted with
caution. Rapid serological tests for the diagnosis
of tuberculosis have sensitivities between 13-92%
and specificities between 66-100%12. A negative
rapid diagnostic test in a patient with low clinical
Indian Journal of Practical Pediatrics
suspicion and a positive AFB smear will be
helpful to eliminate the presence of active
infection. Conversely a positive rapid test, when
the level of suspicion is moderate with a positive
smear will clinch the issue12.
Hepatitis A
Commonly referred to as infectious
hepatitis, this is caused by a picorna virus. This
spreads almost exclusively through faeco-oral
contact, from person to person through
contaminated food or water. IgM Antibody to the
virus is detectable five days after exposure and
remains detectable for 3-6 months. During the
convalescent phase individuals produce IgG
antibody, which usually remains as a lifelong
marker. Diagnosis is usually made on the basis
of clinical symptoms and signs and the need
for testing more for a confirmation of
diagnosis and identification in those situations
where the ink-filler principle operates. The
affected individual has two or three infections
simultaneously and the clinical picture is totally
confusing. Serological diagnosis is by detection
of IgM antibody or total antibody to Hepatitis A
virus. Several commercially available ELISA kits
are used and usually take about three hours to
perform. These tests are extremely reliable and
offer good degrees of sensitivity and specificity13.
HIV
An emerging area of great concern is that
of vertical transmission of HIV. This is possibly
one situation where rapid tests are most indicated.
Rapid tests for HIV are based on different
principles like particle agglutination, membrane
immuno-concentration, immunochromatography
and ELISA. The sensitivity of these devices is
around 97-100% with specificity of 96%14. Rapid
tests are indicated in certain situations15:
a Pregnant women whose HIV status is
unknown, during the time of delivery so as
28
2003; 5(2):116
to prevent vertical transmission
b People who may have exposed themselves
to an occupational risk (medical and nursing
staff)
c Screening before providing medical
attention.
A negative rapid test result in an area of low
prevalence does not pose a problem. Any patient
with a positive test result on a rapid test needs to
have it confirmed by a western blot.
A HIV antibody positive report in a newborn
needs to be interpreted with caution. In the
newborns blood, maternal IgG is present as,
a)during pregnancy, there is a passive transfer
of maternal IgG antibody to the newborn, b) there
is admixture of small amounts of maternal and
foetal blood and c) there are placental leaks. This
antibody remains detectable in the blood of the
newborn even up to one year, hence these results
should be correlated with the maternal HIV status
when possible. If a conclusive diagnosis of HIV
is required in the newborn, a qualitative
polymerase chain reaction is ideal. With a
qualitative PCR, the sample can be reported
conclusively as either being negative or positive
for copies of the virus.
In adults, rapid testing of saliva and urine for HIV
antibody has become common over the counter
tests in some of the developed countries. The
saliva tests have a sensitivity of 99.5% and those
of urine are 98.7% sensitive and 99.1% specific.
However at a HIV point of care testing
workshop in Canada in March 9916, it was
underlined that since 2/3rd of people who test
positive on rapid testing devices subsequently
tested negative for HIV by the western blot, rapid
testing devices need to be used only in certain
specific situations as the benefits of easy testing
are far outweighed by the enormous anxiety the
individual undergoes before his/her HIV status
is confirmed.

Rapid testing devices are a great innovation,
do save considerable time and can be used in
certain places where sophisticated equipment or
trained personnel are not available. However
wherever and whenever indicated they need
to be confirmed before the report is disclosed
to the patient. They need to be interpreted after
taking into account the prevalence of that
particular infection/disease in the population
under study. All laboratory tests are only guides
to a diagnosis and should be clinically correlated
in all situations.
References
1. Abdul Haque, Jaabaz Ahmed, Javed A Qureshi.
Early detection of typhoid by Polymerase Chain
Reaction. Ann Saudi Med 1999; 19 (4) : 337
340.
2. Malaria Laboratory Diagnosis R P H Labo-
ratory Medicine; 1998 2000
3. Guidelines for the diagnosis and management
of dengue for health care staff in N.Queensland.
Published by the Peninsular and Torres Strait
region, the northern region and the Mackay
region of Queensland health in 1994. Refor-
matted by Keyan Daniell.
4. Sang CT, Cuzzubbo A J, Devine P L. Evalua-
tion of a commercial capture enzyme linked
immuno-sorbent assay for detection of immu-
noglobulin M & G antibodies produced during
dengue infection Clinical Diagnostic Lab Im-
munology 1998, January 5 (1) 7 10.
5. Faine S, Adler B, Bolin C, Perolat P. Leptospira
and Leptospirosis. Chapter 12, Second edition,
MediSci , Melbourne; Sept 1999.
6. Saranya Narayan, Srinivasan P, Padmasree
Ramesh. Leptospirosis - An emerging transfu-
sion transmissible infection. Paper submitted
for presentation
7. Winslow W E, Merry D J, Pirc M L, Devine P
L. Evaluation of a commercial ELISA for de-
29
2003; 5(2):117
tection of IgM antibodies in the diagnosis of
human leptospiral infection. J clini microbiol,
1997; 35 (8) 19381942.
8. Ribeiro M A, Brandao A P, Romero E C. Bra-
zilian J, Evaluation of diagnostic tests for hu-
man leptospirosis, Medical Biological Re-
search, June 1996; 29 (6): 773777.
9. Trollip A, Albert H, Mole R, Hatch S, Blumberg
L. Biotec Laboratories Ltd, South Africa and
UK and South African Institute for Medical Re-
search, Johannesburg, South Africa, Rapid in-
dication of MDR-TB from automated liquid
culture systems using FAST plaque TB-RIFTM
test.
10. Evaluation of the Rapid Line Immuno-chro-
matographic serological assay for presumptive
detection of M.TB infection. Tuberculosis
project 2 4 96, J N International Ltd., My-
cobacterium Tuberculosis diagnostics and vac-
cine projects (1996 2002).
11. Rapid Diagnostic Tests for tuberculosis:
Progress but no gold standard An editorial
Am J. Resp. Crit. Care Med, 1997;155: pp 1497
98.
12. Dr.V.H. Balasangameshwara, Rapid diagnos-
tic tests for tuberculosis, Pre-congress work-
shop on rapid diagnostic test in clinical micro-
biology 6th Nov 1998, IAMM, Manipal.
13. Viral Hepatitisan epidemic in the making.
Monograph provided by American Diagnostic
Health Foundation in cooperation with Ameri-
can Liver Foundation.
14. Bernard M, Brasson MD. Rapid tests for HIV
Antibody, AIDS Review 2000 (in press).
15. Michele E. Roland, Richard Fine, Paul A
Volberding, Indication for the use of HIV An-
tibody tests - April 1998 AIDS Knowledge
Base.
16. Concerns about rapid HIV screening at the
point of care. HIV Point of Care Testing
workshop held by Health Canada March 1999.
Indian Journal of Practical Pediatrics
LABORATORY MEDICINE
NEONATAL METABOLIC
SCREENING
* Nair PMC
Every parent wants to bring a healthy baby
into the world. The advances in medical sciences
has led to a reduction in infectious diseases, so
that genetic and metabolic disorders are
remaining as a major group of disorders
responsible for morbidity and mortality,
especially in neonates. Newborn screening
program identifies biochemical or other inherited
conditions that may produce mental retardation,
other disabilities and/or death. There are 2 types
neonatal screening for high risk neonate, mass
newborn screening. The latter is decided by
discord prevalence in a particlar area and by the
availabilty of laborotary facility reservoiers. The
most commonly accepted diseases needing
neonatal screening are1 Hypothyroidism, Phenyl
ketonuria, Maple syrup urine disease, Biotinidase
deficiency, Galactosemia, Tyrosinemia,
Histidinemia, G6PD deficiency, Sickle cell
disease, Cystic fibrosis, Congenital adrenal
hyperplasia, Homocystinuria
Around 500 metabolic diseases are known
today. Approximately 24 children per one lakh
births have a disease involving amino acids,
organic acids, primary lactic acidosis,
galactosemia or a urea cycle disease2. Recent
advances in the diagnosis and treatment of inborn
errors of metabolism have improved the
prognosis for many of these conditions3,4,5,6. Even
* Consultant Neonatologist,
Child Health Department,
Sultan Qaboos University Hospital,
Muscat, Sultanate of Oman.
30
2003; 5(2):118
with untreatable disorders, it is important to
establish the diagnosis in the index case in order
to allow prenatal diagnosis in subsequent
pregnancies. Hence it is imperative that practicing
paediatricians and neonatologists be familiar with
the clinical presentation and approach to these
disorders.
Clinical recognition of metabolic disease in the
neonatal period
An important key to diagnosis is a high index
of suspicion. The signs and symptoms are quite
nonspecific and subtle in onset or can be stormy.
Consider the possibility of a metabolic disease
in any infant with non-specific symptoms that
are not explicable by another cause.
Look for history of 1) consanguinity (the
majority of metabolic diseases presenting in the
newborn period are autosomal recessive),
2) positive family history of similar disease /
unexplained neonatal deaths in siblings, mental
retardation, developmental delay or intolerance
to certain foods. 3) Most often it is a full term
baby born after an uneventful perinatal period.
Prior to delivery, the fetus is protected from
any ill-effects of a metabolic disease by virtue of
the function of the placenta in providing fuel and
filtering toxic metabolites. It takes some time for
the toxins to build up, so that for the first few
days after birth, the baby is usually asymptomatic.
4) Acute onset with progressive course- starting
with some subtle symptoms like lethargy, poor
feeding, vomiting, hiccoughs, respiratory
distress, apnea, and jaundice that soon progress
to coma, seizures, multi-system failure and death.
5) Not to forget some metabolic diseases like
Long Chain Hydroxy Acyl CoA dehydrogenase

Table I.Unusual odour or smell of urine
Odour Disorder
Musty or mousy odour Phenylketoneuria
Boiled cabbage smell Tyrosinemia
Smell like burnt sugar Maple syrup urine
(Maple syrup) disease
Sweaty feet smell Isovaleric acidemia
Glutaric acidemia
(TypeII)
Cat urine smell Multiple Carboxylase
deficiencies
Rotten fish odor Trimethylaminuria
deficiency (LCHAD) in the fetus affecting the
mother with Acute fatty liver of pregnancy.
Physical examination may yield nonspecific
findings like hypotonia / hypertonia, seizures,
jaundice, hepatomegaly, cardiomyopathy,
dysmorphism or coarse facial features,
abnormalities of the skin, hair, eyes, joints,
unusual urine color, unusual odour of sweat or
urine (Table 1). Acute symptoms maybe
indistinguishable from those of sepsis,
cardiorespiratory failure or CNS disease.
Neutropenia, thrombocytopenia and sepsis
particularly with E.coli may be present. Chronic
symptoms are failure to thrive, developmental
delay or neurological defects.
Patterns of presentation of metabolic disease
in the neonate and clue to diagnosis
Three types of presentation7,8
1) Intoxication type with a window period and
progressive encephalopathy. Neurological
presentation with a symptom-free interval,
followed by lethargy, poor feeding, altering of
conscious state, seizures and coma, is typical of
a) Organic acidemias including Maple syrup
urine disease b) Urea cycle disorders.
2) Energy deficient type with no window
period.
31
2003; 5(2):119
Encephalopathy, seizures and apnea without a
symptom-free interval is typical of
a) Primary lactic acidosis
b) Non-ketotic hyperglycinemia (NKH)
c) Sulphite oxidase deficiency (SOD)
d) Pyridoxine dependency
If associated with profound hypotonia,
dysmorphism and / or congenital anomalies,
myopathy think of a) Peroxisomal disorders b)
Mitochondrial disease
3) Storage type: Hydrops, jaundice,
hepatosplenomegaly and dysmorphism may be
present. eg: Mucolipidoses, Niemann Pick
disease
Cardiac disease: Cardiac failure and
cardiomyopathy, can occur in association with
mitochondrial, lysosomal or fatty acid oxidation
disorders or Pompes disease (GSDII).
Liver dysfunction: Persistent hyperbiliru
binemia (conjugated +/- unconjugated) may be
indicative of a metabolic disease, in particular,
galactosemia but also hypothyroidism,
tyrosinemia, alpha-1-antitrypsin deficiency and
others8.
Dysmorphism: Metabolic diseases
associated with dysmorphic features include
peroxisomal disorders (Zellweger syndrome),
disturbances of energy metabolism(Pyruvate
dehydrogenase deficiency) defects in cholesterol
biosynthesis (Smith-Lemli-Optiz syndrome,
CDG-Carbohydrate deficient glycoprotein
syndromes) and storage disorders8.
Fetal hydrops: A number of metabolic
diseases can cause fetal hydrops but rare.
Approach to the diagnosis of a metabolic
disease (Fig.1)
1. History and clinical information
2. Initial Screening or Primary laboratory tests
(Table II)
Indian Journal of Practical Pediatrics 2003; 5(2):120

Acute neonatal encephalopathy

Non-metabolic causes Metabolic cause

Septicemia 1. Do Blood Ammonia

Meningitis
Hypoxic encephalopathy Very high Normal
Intracranial hemorrhage (>150um/L)
Hypoglycemia MSUD
NKH
2. Do ABG SOD
Peroxisomal disorders

Severe metabolic acidosis Normal/Resp. alkalosis

3.Do Lactate, Pyruvate, Ketones

Urea Cycle disorders

Mixed Keto-Lactic Acidosis Lactic acidosis only

Organic Acidemias
Propionic Acidemia
Methylmalonic Acidemia 4.Do Lactate Pyruvate Ratio
Isovaleric Acidemia
Multiple Carboxylase
deficiency Normal or low (<10) High(>30)

Pyruvate dehydrogenase deficiency 5.Beta(OH)Butyrate/AcetoAcetate ratio

< 2:1 > 2:1

Pyruvate Carboxylase def Resp Chain Defects

Fig 1. Approach to diagnosis Algorithm

i) CBC for neutropenia and thrombocytopenia lactic acidosis

ii) Electrolytes and arterial blood gas to
evaluate for metabolic acidosis and anion
gap
Anion gap = (Na+ + K+) (Cl- + HCO3-)
Normal value = < 15 mEq/L
Metabolic acidosis with increased anion gap,
is suggestive of organic acidemias and primary
32
iii) Blood sugar. Hypoglycemia indicates either
glycogen depletion +/- inadequate
gluconeogenesis (premature or SGA infant)
or hyperinsulinism (infant of a diabetic
mother); occasionally hypoglycemia will be
a manifestation of a metabolic disease eg;
fatty acid oxidation defect, glycogen storage
disease
 2003; 5(2):121

iv) Urine for ketones, reducing substance and
ferric chloride test. Presence of urinary
ketones is suggestive of organic acidemia
and absence of which may denote fatty acid
oxidation defects. If reducing substance in
urine is positive, interpret it carefully,
because of the chance of high false positivity.
Remember that glucose is a reducing
substance. So if the clinitest is positive
(Clinitest detects all reducing substances
including glucose), check the urine
specifically for glucose using a glucose
oxidase strip. Urine dipsticks detect glucose
only. Ferric chloride test for ketoacids is
positive in Phenyl ketonuria, Tyrosinemia,
Maple syrup urine disease, Histidenemia,
and Alkaptonuria. The test is non-specific
and not used in modern laboratories.
v) Low blood urea: Signifies urea cycle
disorders
vi) Uric acid is elevated in glycogen storage
type Ia and low in molybdenum co factor
defects.
vii) Serum ammonia : If hyperammonemia
(>150umol/L) is detected in a newborn less
than 24 hours of age, think of transient
hyperammonemia of newborn, if preterm
and Pyruvate dehydrogenase deficiency
(PDH),if full-term. After 24 hours of age,
hyperammonemia associated with keto-
acidosis, is suggestive of Organic acidemias
and with normal blood gas or alkalosis is
suggestive of Urea cycle disorder.
For accurate values, rapidly flowing blood
(arterial stab) should be collected, placed in
ice and carried to the lab immediately. It
should be done within 1 hour. Hence prior
notification to the lab is necessary.
viii) Blood lactic acid, pyruvic acid and lactate
pyruvate ratio.
If arterial lactate is persistently high
(>3mmol/L), the differential diagnosis is:

Table 2. Laboratory tests

Screening Laboratory Tests Confirmatory Tests

Disorders Blood gas Urine Lactic Serum Blood TMS Urine GCMS
Anion gap Ketones Acid Ammonia AA & Acyl (Organic Acids)
carnitine
MSUD - + - - + Not indicated
Organic Severe ++ + + + +
Acidemias acidosis
Primary Severe +/- +++ + + +
Lactic acidosis
Acidosis
Urea Cycle Resp - - +++ + Not indicated
Disorders alkalosis
Non-ketotic - - - - + Not indicated
hyperglycin
-emia
(+) abnormal test (-) normal test
AA-Amino acids; MSUD- Maple Syrup Urine Disease
TMS- Tandem mass spectrometry
GCMS - Gas chromatography & mass spectrometry
33
Indian Journal of Practical Pediatrics 2003; 5(2):122

Table 3. Differential diagnosis of common metabolic disorders:

Diseases Clinical features Biochemical Confirmatory tests
abnormalities
Maple Syrup Urine smell, Neuro- Urinary Di-nitro phenylhydrazine;
Urine disease intoxication, tone ketones++ Aminoacid profile; TMS
changes, seizures Hypoglycemia+/-
(in first wk of life)
Organic acidemia Neuro-intoxication U.Ketones++ TMS
(within first month) Acidosis+++ Urine GCMS
Ammonia+
Lactate+
Pancytopenia
Urea cycle Intoxication type No ketosis TMS
disorders (in first week of life) Respiratory Aminoacid profile;
alkalosis Urine Orotic acid
Ammonia+++
Cong Lactic Energy deficiency Acidosis++ Lactate Pyruvate ratio;
Acidosis (since birth) Ketosis++ except B-OH.B/AA ratio;
in PDH Urine GCMS
NKH Energy deficient type, Normal CSF & Blood Amino acid profile,
SOD Myoclonic seizures, TMS, Urine Sulfitest; Plasma
Peroxysomal Severe hypotonia very long chain fatty acids
Disorders (since birth)
Galactosemia Hepatomegaly Hypoglycemia Enzyme studies
Fructosemia Hypoglycemia Cholestatic Urine GCMS
Tyrosinemia Jaundice, Fanconi jaundice;
syndrome (in first few Urine reducing
months of life) substance
Glycogen Hepatomegaly Hypoglycemia Enzyme studies
storage Hypoglycemia Lactate++
disease No jaundice Uric Acid+
Fatty acid Energy deficiency Non ketotic TMS
oxidation Hepatomegaly acidosis
defects (in first year) Hypoglycemia
TMS- Tandem Mass Spectrometry, GCMS-Gas chromatography mass spectrometry;
B-OH-B/AA Beta hydroxy butyrate and aceto acetate ratio;
NKH- Non-ketotic hyperglycinemia; PDH- Pyruvate dehydrogenase deficiency;
SOD- sulphite oxidase deficiency

34

a) severe organ dysfunction leading to decreased
tissue perfusion/oxygen delivery or increased
metabolic demand as in perinatal asphyxia,
congenital heart disease (duct dependent lesions),
sepsis or untreated seizures.
b) Primary lactic acidoses like disorders of
pyruvate metabolism, mitochondrial disorders
c)Secondary lactic acidoses Other metabolic
diseases may be associated with lactic acidosis
like fatty acid oxidation defects, organic acidoses
etc.
ix) Urine for metabolic screen : 5-10 ml freshly-
collected urine in a sterile container with no
preservatives; can be frozen prior to analysis
if necessary.
Filter paper technique for collection of
capillary blood by heel prick: Spot 1 to 2 drops
of blood onto each of the 3 circles on the specific
filter paper provided, until the circles are filled
completely. Then let the blood spots to dry in
air. Blood spots can now be used for the diagnosis
of a large number of inherited metabolic
disorders.
Before doing the primary investigations,
ensure that the patient is well fed with an adequate
protein diet 2-3 hours before. Neonates should
be given milk feed. Primary investigations for
inborn errors of metabolism must be carried out
as a matter of urgency and if indicated out of
hour also. The specimens should be collected
during the acute episode before starting treatment.
If the above simple primary investigations
are normal in a patient that is well fed, the chance
of a metabolic disease as the cause of illness is
low.
Advanced Screening tests (Table 2)
1. Tandem Mass Spectrometry (TMS)
2. Plasma Amino acid and urine Chromatography
35
2003; 5(2):123
3. CSF analysis for organic and amino acids
Tandem mass spectrometry is the most
significant advance in newborn screening in the
past 30 years 9 . While gas and liquid
chromatography is time consuming, using tandem
mass spectrometry, more than 30 disorders can
be easily detected from a drop of blood on filter
paper in a single test within 1 to 2 minutes. It
detects molecules by measuring their weight
(mass) electronically and display results in the
form of a mass spectrum (graph showing each
specific molecule by weight and how much of
each molecule is present)10.
Definitive diagnostic tests include specific
enzyme analysis, assays for galactose 1-
phosphate uridyl transferase , DNA testing on
liver, muscle, or skin biopsy specimens.
Emergency management of a suspected
metabolic disease
It is essential that the treatment of patients
with inborn metabolic disease is started without
delay in order to avoid irreversible damage to
vital organs, especially the brain, and fatal
outcome in neonates where the clinical course
can be rapid.
1. Stop all oral feeds after collecting the necessary
tests. Collect 3 drops of blood on filter paper for
Tandem MS. Collect 10 ml urine and deep freeze
immediately for organic acids by gas
chromatography mass spectrometry (GCMS).
2. Monitor vital signs and biochemical parameters
periodically
3. Treat sepsis if indicated.
4. Prevent dehydration and catabolism by giving
full maintenance fluid as 10% glucose with
electrolytes
5. Start next day intralipids and a small amount
of amino acid mixtures (maximum 0.25 to 0.5
Indian Journal of Practical Pediatrics
gm/kg/day) to prevent endogenous protein
breakdown.
6. Treat metabolic acidosis if pH <7.2
7. Hyperammonemia (Ammonia >150umol/L)
always warrant urgent treatment, as every minute
delay can cause neuronal damage.
Priming (stat) dose :
Sodium benzoate 250mg/kg; Phenyl acetate
250mg/kg; Arginine 660mg/kg (in urea cycle
disorders only) all diluted in 25ml/kg of
10%Dextrose and infused over 90 minutes.
Maintenance dose: Same dose and dilution but
infused over 24 hours.
8. IV Carnitine. Useful in organic acidemias by
removing toxic organic acids and restoring
mitochondrial functions.
9. Use of soluble insulin is anabolic and prevents
hyperglycemia from use of high glucose
concentrations (0.1 units/kg/hr with monitoring
of blood sugar)
10. Specific treatment include cofactor biotin and
Propimex-1 formula for Propionic acidemia,
Thiamine and Ketonex-1 formula for Maple
syrup urine disease, High carbohydrate diet and
biotin for Pyruvate carboxylase deficiency etc.
Conclusion : IEM is an extremely challenging
area. For successful management, awareness,
early suspicion, and a good regional center with
facilities for accurate early diagnosis and prompt
treatment including availability of special milk
formulas, are mandatory.
ERRATUM
In the issue 2003;5(1), in page 81, under questions and answers column in the Answer 4
regarding need for Tet Vac, it should be read as Skunks instead of snakes and Ferrets
instead of parrots.
36
2003; 5(2):124
References
1. Chakrapani A, Cleary MA, Wraith JE. Detec-
tion of inborn errors of metabolism in the new-
born. Arch Dis Child 2001; 84: F205-210
2. Applegarth DA, Toone Jr, Lowrt RB. Incidence
of Inborn errors of metabolism I British Co-
lumbia, 1969-1996. Pediatrics,2000;105:10
3. Burton BK. Inborn errors of metabolism in in-
fancy: a guide to diagnosis, Pediat-
rics,1998;102:69
4. Ward JC. Inborn errors of metabolism of acute
onset in infancy. Pediatr. Rev,1990; 2:205
5. Walter JH. Inborn errors of metabolism and
pregnancy. J Inherit Metab Dis, 2000; 23:229-
236
6. Diagnosis and treatment of Maple syrup urine
disease: a study of 36 patients. Pediatrics, 2002;
109(6):999-1008
7. Irons, M. Screening for metabolic disorders.
How are we doing? Pediatr Clinics of North
America, 1993; 40:1073-1085
8. Levy, H.Screening of the newborn. In Diseases
of the Newborn. WB Saunders Co. Philadel-
phia, 1991.6th ed: 111-146
9. Naylor EW, Chace DH. Automated tandem
mass spectrometry for mass newborn screen-
ing for disorders in fatty acid, organic acid, and
amino acid metabolism. J Child Neurol,
1999;14 Suppl 1: S4-S8
10. Wiley V, Carpenter K, Wilcken B. Newborn
screening with tandem mass spectrometry : 12
months experience in NSW Australia. Acta
Paediatr Suppl,1999; 88:48-51

LABORATORY MEDICINE
LABORATORY DIAGNOSIS OF
PERSISTENT AND CHRONIC
DIARRHEA
* Shinjini Bhatnagar
Persistent Diarrhea
The duration of acute diarrhea forms a
continuum, most episodes terminating within 7
days and progressively smaller proportions
persisting beyond 14, 21 or 28 days. The
delineation of persistent diarrhea from acute
diarrhea is arbitrary. The most commonly used
definition is an episode that begins acutely, is of
a presumed infectious etiology and persists for
14 days or more. The pathogenesis is
multifactorial with persistent mucosal injury
being the hallmark of the disease. The common
etiological factors are persistent or recurrent
infection with enteropathogens namely Shigella,
Salmonella, enteroadherant E.coli or small bowel
bacterial overgrowth. Secondary lactose or
carbohydrate intolerance due to a combination
of macro and micronutrient deficiency and enteric
infection, and infrequently secondary milk
protein intolerance further perpetuates the
mucosal injury and prolongs diarrhea. Several
randomized controlled studies have shown that
antimicrobials offer modest or no clinical benefit
in persistent diarrhea. Nutrition is the mainstay
of treatment. A dietary algorithm using a stepwise
elimination of carbohydrates is recommended by
the WHO and the National Task Force on
diarrhea1.
* Centre for Diarrheal Diseases and Nutrition
Research, Department of Pediatrics,
All India Institute of Medical Sciences, New
Delhi
37
2003; 5(2):125
Lab diagnosis of persistent diarrhea
Patients with persistent diarrhea can be
managed without elaborate laboratory tests using
the above algorithm with very high levels of
success. Stool microscopy helps in identifying
trophozoites of E.histolytica and G.lamblia,
which are present in a very small proportion of
children. Majority of children who have cysts of
E.histolytica are now known to have non-
pathogenic E.dispar. Large number of pus cells
(> 20 /HPF) in stool suggest invasive diarrhea
but the specificity of this test is low and a majority
of children with persistent diarrhea do not have
these.
Stool cultures are expensive and not
warranted in all cases. They should be ordered
only when there is a high index of suspicion for
Shigella or Salmonella especially in very young
infants. Isolation of E.coli is not helpful as most
laboratories cannot characterize for virulence
properties.
In a non-hospital setting, detecting reducing
substances is often impractical as tests cannot be
done promptly and several stools need to be
examined for sufficient sensitivity. In these
settings it is, therefore, more practical to use
clinical criteria to decide on change in diet as
shown in the algorithm (Fig.1). The fact that
diet-A has reduced lactose already assumes that
some secondary lactose intolerance exists in
children with persistent diarrhea2. However,
wherever possible stools should be tested for pH
and reducing substances (see details of methods
below) as it documents carbohydrate intolerance.
Indian Journal of Practical Pediatrics 2003; 5(2):126

Treat dehydration and any associated systemic infection

Start Diet A* [low lactose milk cereal mix]


Success Treatment failure

Start Diet B* [milk free; mixes of complex carbohydrates
disaccharides, milk free proteins and oils]

Discharge Success Failure

Start diet C* (monosaccharide based diets)

Resume appropriate diet for Start Diet C [After screening age 7-14 days later
& treating systemic infection]
*Screen and treat for systemic infection
Fig 1. Dietary algorithm for treatment of persistent diarrhea

A skilled microscopist and careful attention

Chronic Diarrhea
Diarrhea that has persisted beyond 6-8
weeks is defined as chronic and the etiology may
differ by age3.b (Table 1)
IMPORTANT LABORATORY
DIAGNOSTIC STUDIES
Initial screening tests - Stool examination
The initial studies would include stool
examination for blood, leucocytes, protozoa and
reducing substances. Identification of fecal
leukocytes, red blood cells or occult blood
suggests an inflammatory condition of the lower
colon. Fecal leukocytes are detected on
examining direct smears or after staining with
3% Loefflers methylene blue. The smear should
be allowed to stand for two or three minutes for
good nuclear staining. All differential counts
should be made under high power, counting 200
cells when possible. Only those cells clearly
identified as either mononuclear or polymorho
nuclear are included in the differential count.
38
to the collection and preservation of stool samples
is important for diagnosing enteric parasites.
Presence of radio contrast material like barium,
antacids, mineral oil or antibiotics may interfere
with the detection of protozoa and a period of 2
weeks without any of these substances would be
advisable before collecting the stools. Further,
contamination with water or urine can result in
lysis of trophozoites. Examining multiple samples
obtained on separate days increases the sensitivity
of detection because of variable shedding of cysts
and trophozoites 4. Sensitivity of detecting
Giardia trophozoites, cysts or antigens increases
by about 20% (about 70% if a single stool sample
is examined) if three stool samples are examined.
Giardia is detected on direct smear or after
concentration with 10% formol-ether.
Examination of a fresh stool is ideal for
identification of motile trophozoites.
Routine ova plus parasite examinations do
not include tests for Cryptosporidium parvum and
other new enteric spore forming protozoa like
isospora and cyclospora and need to be specially
asked for. Cryptosporidium parvum occurs in

Table 1. Causes of chronic diarrhea in different age groups
Neonatal diarrhea
Anatomic causes
Congenital short-bowel syndrome
Malrotation with partial blockage
Hirschsprungs disease
Congenital microvillus atrophy
Tufting enteropathy
Neonatal lymphangiectasia
Inherited transport defect
Glucose-galactose malabsorption,
Congenital chloridorrhea,
Bile-salt malabsorption
Milk enterocolitis
Age 1 mo to 2 y
Post viral or bacterial gastroenteritis e.g. lactose
intolerance, zinc and other nutrient deficiency
Persistent infection with Shigella, Salmonella,
enteroadherant E.coli, Giardia lamblia,
Cryptosporidium, small bowel bacterial
overgrowth
Cows milk, soy and other allergy
Celiac disease
Irritable colon of infancy (chronic non-specific
diarrhea)
Cystic fibrosis
upto 12% of immunocompetent children with
diarrhea and upto 24% in immunocompromised
hosts especially those with AIDS in developing
countries5. At least 5-6 stools should be collected
in 10% formalin or sodium acetate-acetic acid-
formalin (SAF) on separate days. Staining with
modified Kinyouns acid-fast stain is usually the
method of choice for clinical microbiological
laboratory while negative staining with Giemsa
and concentration methods are restricted for
research purposes6. A stool is considered positive
for Cryptosporidium parvum if typical oocysts
4-6 m in diameter are identified while the
cyclospora and isospora oocysts are larger and
vary from 10-30 m in diameter respectively.
39
2003; 5(2):127
C. difficile, (antibiotic-associated diarrhea)
VIP secreting tumors
Immunodeficiency: common variable, severe
combined, X-linked agammaglobulinemia,
transient hypoglobulinemia
Autoimmune enteropathy
Age 2 y to 18 y
Celiac disease
Inflammatory bowel disease
Post-infective persistent diarrhea with Shigella,
Salmonella, enteroadherant E.coli, Giardia
lamblia, Cryptosporidium, small bowel bacterial
overgrowth
Chronic non-specific diarrhea (Irritable bowel
syndrome)
Primary acquired lactase deficiency
Tropical sprue
Chronic pancreatitis/exocrine pancreatic
deficiency
Primary or secondary lymphangiectasia, hypo/
abetalipoproteinemia
Acquired immunodeficiency
Constipation with encopresis
Antibiotic-associated C. difficile
VIP secreting tumors7
Kinyoun acid fast stain
Freshly passed stool is emulsified in 5 ml
of 10% normal saline and filtered through two
layers of gauze. 4 ml of solvent ether is added
to the filtrate, mixed well and centrifuged at
1500 gyrations for 5 minutes. The supernatant
is decanted leaving 1-2 drops with the sediment.
Smears are made from the thoroughly mixed
sediment on glass slides, fixed in methanol after
air drying and are examined under oil
immersion.
Enzyme linked immunoassay tests for
antigens in stool for Giardia and Cryptosporidium
Indian Journal of Practical Pediatrics
are highly sensitive and specific but are not
routinely available.
Clostridium difficile diarrhea is uncommon
in children but wherever the index of suspicion
is high, stool should be examined for the
pathogen. The tissue culture assay for cytotoxin
B is the gold standard but is expensive and
cumbersome. Rapid toxin ELISA assay has
comparable sensitivity and specificity to those
of the tissue culture assay and can be read within
hours.
Acidic stools with pH of less than 5.5 and/
or positive for reducing substances usually
indicate carbohydrate malabsorption and
proximal small bowel damage. Small bowel
mucosal injury results in malabsorption of
carbohydrates. The unabsorbed carbohydrates in
the small intestine are fermented by colonic
bacteria producing organic acids, carbon dioxide
and hydrogen gas. The organic acids get oxidized
and absorbed in the colon. This fermentative
action, which reduces the osmotic load of
malabsorbed carbohydrates and may benefit the
host by salvaging calories, is known as the
colonic salvage mechanism. Therefore the liquid
stool seen in carbohydrate intolerance is
characterized by an acid pH due to organic acids,
mainly lactic acid and by the presence of
unabsorbed sugars. The tests for identifying
acidic stools are valid only if the childs diet
contains sufficient quantities of carbohydrates.
Stool pH provides an indication to the amount of
organic acids in stool while the increased amounts
of reducing substances indicate the presence of
unabsorbed sugars. Sucrose is a non-reducing
sugar and will react in this test only after it has
been acted upon by the colonic bacteria.
Detection of stool pH and reducing substances is
an important diagnostic tool in infants but may
not be helpful in older children as they have a
better colonic salvage mechanism. Presence of
reducing substances in stool of neonates
40
2003; 5(2):128
Detection of reducing sugars in stool
1 ml distilled water is added to 0.5 ml liquid
stool and shaken well. Eight drops of this
solution is added to 5ml of pre-boiled benedicts
solution and is boiled for 1 minute. The solution
is cooled and the colour of the precipitate is
examined:
The reducing sugars in stool are graded as
follows:
No colour change: nil
Green precipitate: 0.5%
Yellow precipitate: 1.0%
Orange precipitate: 1.5%
Brick red precipitate: > 2.0%
For detection of non reducing substances in
stool 1 ml N/10 HCl (instead of distilled water)
is added to 0.5 ml liquid stool and boiled for 1
minute. The HCl splits the non-reducing to
reducing sugars. The subsequent steps are as
shown above.
particularly those who are exclusively breast-fed
and pass liquid stools may be normal because of
a physiological malabsorption of lactose during
the neonatal period which has no nutritional
significance.
Lactose hydrogen breath test that detects the
presence of hydrogen in the breath after giving a
lactose dose of 2g/kg (to a maximum of 50g) is
another useful diagnostic tool for documenting
carbohydrate malabsorption. A rise in hydrogen
excretion greater than 20ppm 1-3 hours after the
oral dose represents a positive peak and is
produced by the fermentation of unabsorbed
carbohydrates by the colonic bacteria.
Stool osmotic gap can be measured to
determine the osmotic nature caused by
unabsorbed carbohydrates. The osmolality
(mOsm/kg) and the fecal concentrations of
sodium and potassium (mEq/l) of a fresh liquid

stool sample is measured and the osmotic gap is
calculated as:
Osmotic gap = stool osmolality (approximately
290 mOsm/kg) 2 (stool sodium + stool
potassium). There is an osmotic gap due to the
malabsorbed carbohydrates when the difference
is greater than 50 mOsm/kg. Stool sodium
concentrations greater than 90 mEq/L and an
osmotic gap less than 50 mOsm/kg indicates a
secretory diarrhea. These are specialized tests and
maybe used in hospital settings in more
complicated cases to differentiate conditions
leading to osmotic (e.g. secondary carbohydrate
intolerances, infrequently intestinal transport
defects) or secretory diarrhea (infections,
infrequently congenital chloride and sodium
diarrhea or neural crest tumors).
Sudan III stains fat globules in stool and is
a quick and simple way to screen for fat
malabsorption (Drummeys method). It is a
qualitative test and indicates gross steatorrhea.
Chemical analysis of fat in stool per 24 hours
collected over 72-hours using Van de Kamer
method gives an accurate quantitative
measurement of fat malabsorption. The child
should be on a high fat diet (at least 50g/day)
during the test. Co-efficient of fat absorption/
retention can be calculated if the 72 hour dietary
intake of fat is available as:
(Dietary fat fecal fat)
X 100
Dietary fat
The reference limits for fecal fat losses are
< 7% of daily fat intake for children > 6 months
of age and < 15% of intake for younger infants.
Presence of severe steatorrhea would
suggest an exocrine pancreatic deficiency. Mild
or moderate fat malabsorption may be present in
chronic infections like giardiasis or in celiac
disease and other enteropathies.
41
2003; 5(2):129
Iron deficiency anemia is common in
conditions where there is iron malabsorption or
chronic intestinal blood loss particularly in celiac
disease, inflammatory bowel disease and cystic
fibrosis. Megaloblastic anemia maybe present
in untreated celiac disease due to chronic
malabsorption of folate and B12. Inflammatory
bowel disease may have anemia of chronic
disease. Low levels of total protein and albumin
may reflect the nutrition status.
Hypoalbuminemia may be seen in intestinal
lymphangiectasia. and inflammatory bowel
disease. An elevated erythrocyte sedimentation
rate suggests an inflammatory bowel disease.
Sudan III staining for fat malabsorption
2 drops of normal saline is added to one
drop of stool on a clean glass slide and is mixed
well with a stirring stick. Two drops of 95%
ethyl alcohol is added to this mixture followed
by two drops of Sudan III stain. :Neutral fats
appear as orange or red drops.
A rough grading is as follows:
Severe : > 100 big (> 6 m in diameter)
droplets / hpf
Moderate: < 100 big droplets /hpf
Mild : < 100 small (< 6 m in diameter)
droplets /hpf
Fatty acids and soaps do not stain but appear as
amorphous flakes or coarse crystals
Blood and urine d-xylose
D-xylose is a pentose sugar, which is
absorbed passively across the proximal intestinal
mucosa without requiring intestinal brush border
or pancreatic enzymes and bile salts. Its
absorption is a measure of the functional surface
area of the intestinal mucosa. A standard dose
of 14.5g/m2 body surface up to a maximum of
25 g is given by mouth. About 50% is
metabolized in the liver and the remaining is
Indian Journal of Practical Pediatrics
Fig 2. Cryptosporidium oocysts seen in
modified acid-fast stain
excreted in the urine. The serum d-xylose levels
of 25g/L at one hour and excretion of > 20% of
the oral d-xylose dose in urine collected for 5
hours after giving the oral dose indicates a normal
functioning mucosa (Reiners method). Although
d-xylose is a non invasive screening method for
assessing proximal intestinal mucosal surface
area, its low sensitivity and specificity limits its
use. It would be a good test for differentiating
between exocrine pancreatic dysfunction and an
abnormal intestinal mucosa. A normal d-xylose
test in the presence of decreased serum pancreatic
enzymes like trypsinogen would suggest a
pancreatic dysfunction.
SECOND PHASE TESTS
Intestinal biopsy
Endoscopic biopsies are obtained from the
first part or midduodenum as compared to the
earlier capsule biopsies, which were taken from
the dudeno-jejunal flexure. Intestinal biopsy is
an essential diagnostic tool in chronic diarrhea
and evaluates the crypt villus structure, epithelial
abnormalities and mucosal inflammation.
42
2003; 5(2):130
Fig 3. Characteristic fluorescent honey-
combing seen around the smooth muscle
bundles on the monkey esophagus indicating
a positive antiendomyseal test on IFA assay
Characteristic histological features of celiac
disease include partial or total villus atrophy,
elongation of the crypts, increased crypt mitotic
index, increased intra-epithelial lymphocytes
with a lymphocytic mitotic index above 0.2%,
infiltration of plasma cells, lymphocytes, mast
cells and eosinophils in the lamina propria, loss
of nuclear polarity with pseudostratification of
epithelial cells and absence of a brush border7.
Well-defined histological features are seen in
intestinal lymphangiectasia, giardiasis,
cryptosporidiosis (Fig 2.), abetalipoprotenemia,
acrodermatitis enteropathica. Cryptosporidium
oocysts are identified on hematoxylin and eosin
stained sections as rows or clusters of spherical
structures attached to the microvillus border of
the epithelial cells. In the small intestine the
lateral aspects of the villi have the maximum
number of oocysts. Significant mucosal
inflammation indicates infections, immunode
ficiency, autoimmune enteropathy or protein
sensitive enteropathies. In the absence of an
abnormal mucosal histology or inflammation,
exocrine pancreatic deficiency, hormonally
mediated secretory tumors, colonic causes or

primary transport defects should be considered.
Colonic biopsies are essential for diagnosing
inflammatory bowel disease.
Serology
Serological tests are important adjuncts in
the diagnosis of celiac disease and are available
in reference laboratories in our settings. Serum
IgG and IgA anti gliadin antibodies (AGA) were
the first generation serological antibodies and are
detected in an ELISA using crude gliadin extract.
The specificity of both IgG and IgA AGA is about
80% in studies done at our centre but the
sensitivity of IgA is higher (90%) than that of
IgG (76%). IgA anti reticulin detected by
immunoflorescence (IFA) on rat kidney are
highly sensitive (>90%) and specific (>90%) but
cumbersome and expensive. Serum anti IgA anti
endomyseal antibodies (EMA) directed against
the reticulin like tissue around the smooth muscle
fibres are detected in an IFA assay using the
monkey esophagus (Fig 3). The sensitivity (91%)
and specificity (95%) of these antibodies is high
in our settings and is consistent with the west.
Human umbilical cord is now being used as a
substrate instead of the more expensive and
inaccessible monkey esophagus with similar
results. Because the test for EMA uses IFA it
can be operator dependent and needs specialized
laboratories and experienced hands. It may also
be less reliable in children less than 2 years. IgA
AGA and EMA are IgA dependent antibodies
and will be negative in individuals with selective
IgA deficiency, which is present in 3% of celiac
disease. The most recent anti transglutaminase
(tTG) antibodies, which is now considered the
main autoantigen for EMA, is measured by
ELISA, a more objective and easily available test
than the IFA8. Both guinea pig and human tTG
have been used as antigens in the ELISA with
results comparable to those of EMA in IFA assay.
Serological tests for detection of circulating
pANCA are a useful diagnostic tool for ulcerative
43
2003; 5(2):131
colitis and helps in differentiating it from other
colitides and also Crohns disease.
Testing for exocrine pancreatic insufficiency
Quantitative measurement of 72-hour fecal
fat collection that demonstrates less than 90%
absorption of the fat ingested is a simple test to
document exocrine pancreatic insufficiency.
These patients would have a normal d-xylose and
intestinal mucosa on biopsy9. Measurement of
fecal concentrations of the pancreatic enzymes
trypsin or chymotrypsin is an indirect measure
of pancreatic function but these measurements
are limited by proteolytic degradation. The
ELISA for human fecal elastase is an alternative
fecal test of pancreatic dysfunction. It is
decreased in exocrine pancreatic deficiency. It
has been seen that values > 100 g /g stool have
99% predictive value for ruling out pancreatic
insufficiency 10 . Serum concentrations of
immunoreactive trypsinogen. determined by
radio immunoassay is a highly sensitive test for
establishing pancreatic insufficiency but is not
very specific. Values < 28 ng/ml are suggestive
of pancreatic insufficiency. The gold standard
remains the estimation of duodenal fluid enzymes
and bicarbonate collected after stimulation with
secretin-pancreozymin or liquid feeding. Marked
reduction of the enzymes reflects severe damage
to the acinar cells, usually when 60% of the
exocrine function is lost. Decreased levels of fat-
soluble vitamins and cobalamin indicate chronic
pancreatic insufficiency.
Elevated concentrations of sodium and
chloride in sweat stimulated by the pilocarpine
iontophoresis is an important diagnostic tool for
cystic fibrosis. However in infants and during
the cold winter months collection of sweat maybe
a problem. Further molecular diagnostic
techniques are used for confirming the diagnosis
of cystic fibrosis.
Indian Journal of Practical Pediatrics 2003; 5(2):132

THIRD PHASE TESTS 4. Hiatt Ra, Markell EK, Ng E. How many stool
examinations are necessary to detect pathogenic
Serum immunoglobulins and other intestinal protozoa? Am J Trop Med Hyg
extensive immunological tests to determine 1995;53:36-39.
immunodeficiency, measurement of anti- 5. Current WL, Garcia LS. Cryptosporidiosis.
intestinal epithelial antibodies in the serum in Clin Microbiol Rev 1991; 4:325-358.
suspected autoimmune enteropathy and
6. Chen X, Keithly JS, Paya C, LaRusso NF.
circulating VIP levels for neural crest tumors may
Cryptosporidiosis. N Engl J Med 2002; 346:
be required for a small number of patients.
1723-1730.
Special staining of biopsies and electron
microscopic evaluation is useful for diagnosis of 7. Bhatnagar S, Cameron DJS, De Rosa S, Maki
microvillus inclusion disease and tufting M, Russell GJ, Troncone R. Recommendations
of the Working Group on Celiac Disease. J
enteropathy.
Pediatr Gastroenterol Nutr 2002; 35(2): S78-
References 88.
8. Molberg O, Mcadam S, Korner R, et al . Tis-
1. International working group on persistent di-
sue Transglutaminase selectively modifies glia-
arrhoea. Evaluation of the efficacy of an algo-
din peptide that are recognized by gut derived
rithm for the treatment of persistent diarrhoea :
T-cells in celiac disease. Nat Med 1998; 4:713-
A multicentric study. Bull WHO 1996;74:479-
717.
489.
9. Toskes PP, Greenberger NJ. Disorders of the
2. Bhatnagar S, Singh KD, Sazawal S, Saxena SK,
pancreas. In: Harrisons principles of internal
Bhan MK. Efficacy of milk versus yogurt feed-
medicine, 15th edn, eds Braunwald E, Fauci A,
ing in acute non-cholera diarrhoea among mal-
Kasper D, Hauser S, Longo D, Jameson J. ,
nourished children. J Pediatr 1998; 132:999-
McGraw Hill Companies, USA (pub), 2001;
1003.
pp 788-1792.
3. Vanderhoof JA. Diarrhea. In: Pediatric gas-
10. Bebarry S, Ellis L, Corey M, Marcon M, Durie
trointestinal disease:pathophysiology, diagno-
P. How useful is fecal pancreatic elastase 1 as
sis, management, Wyllie R, Hyams JS (ed). WB
a marker of exocrine pancreatic disease. J
Saunders company, USA, (pub) 1999, p-32-42.
Pediatr 2002;141:84-90.

NEWS AND NOTES

PAED ENDO- 2003
Paediatric Endocrinology for Practicing Paediatricians
and Postgraduates - An Update
Organised by
Paediatric Endocrinology Division- Institute of Child Health and Hospital For Children, Chennai-8
Indian Academy of Pediatrics-Chennai City Branch
Indian Academy of Pediatrics-TNSC
Date : 26th July 2003 - Saturday Delegate Fee Rs. 300/-
Venue : Savera Hotels Ltd., Dr. Radhakrishnan Salai, Chennai - 600 004.
Delegate Fee (Cash, Cheque Or Draft) to be drawn in favour of Paed Endo and send to
Dr P. Venkataraman, Organising Secretary-Paed Endo 2003
IAP TNSC Flat, F Block, Ground Floor, Halls Towers, 33, Halls Road, Egmore, Chennai- 8
Phone: 28190032, 28191524 Cell:98401 19237

44
 2003; 5(2):133

LABORATORY MEDICINE

LABORATORY EVALUATION OF secondary unless proved otherwise and every step

HYPERTENSION should be taken to find out the cause.
Management of the cause is mandatory in
addition to management of hypertension.
* Vijayakumar M Treating elevated BP without managing the cause
** Prahlad N if treatable will not make proper sense.
*** Nammalwar BR
Blood pressure is an important basic
Introduction physical sign as are the body temperature, pulse
rate and respiratory rate. The measurement of
The interest of pediatricians in
blood pressure is now firmly established as an
hypertension has increased markedly in the last
essential component of routine pediatric physical
two decades essentially due to recent
examination. It is mandatory for every child,
developments in the field of medicine. Primary
three years of age and older to have as a part of
hypertension, which was considered a disease of
routine continuing medical care, a yearly blood
an adult, is also being documented in children.
pressure measurement. In addition acutely ill
Essential hypertension in adults may be preceded
children, regardless of age should have a blood
by high BP of childhood. Control of blood
pressure reading performed at the time of
pressure in children and hence, prevention of end
evaluation. Investigation of a child with
organ damage in adulthood can be done easily.
hypertension depends not only on the severity of
Lifestyle modification in terms of diet, salt
hypertension but also whether the child is
restriction, exercise and stress can be introduced
symptomatic and hypertension is the suspected
early in childhood to have full benefit in
cause. Possible investigatory procedures range
adulthood. Hence, measuring BP regularly as a
from routine tests available in most hospitals to
part of routine care of each child and adolescent
more refined invasive procedures available in
should be the rule in pediatric care. Finding out
specialized units1.
the cause for hypertension is the most important
aspect of management. Detailed clinical history, Goals of evaluation
essential clinical examination, initial There are five major goals of initial
investigations followed by appropriate evaluation of hypertension in children2,3.
investigations based on clues obtained from the
previous steps are needed. Cause of hypertension 1. To establish whether hypertension is sustained
in children should be always considered and might benefit from treatment
2. To identify coexisting diseases
* Pediatric Nephrologist,
3. To characterize the risk factors
** Fellow in Nephrology,
4. To identify the presence and severity of target
*** Chief Nephrologist
organ damage
Kanchi Kamakoti CHILDS Trust Hospital,
5. To identify curable causes of the hypertension
Chennai 600 034.
45
Indian Journal of Practical Pediatrics 2003; 5(2):134

Definition of hypertension4 Table 1. Common causes of childhood

hypertension
Normal BP: Systolic blood pressures (SBP) and
diastolic blood pressures (DBP) below 90 th Neonate
percentile for age, sex and height.
Renal malformation
High normal BP: Average SBP and/or average Coarctation of aorta
DBP between 90th and 95th percentile for age, sex
Renovascular hypertension following
and height.
umbilical artery catheterisation
High BP (Hypertension): Average SBP and/or Bronchopulmonary dysplasia
average DBP above 95th percentile for age, sex Infancy to 6 years of age
and height on three occasions.
Renal parenchymal disease
Causes of hypertension in children Renal artery stenosis
Coarctation of aorta
One should know the common causes of
hypertension in various age groups to decide on 6-10 years of age
diagnostic evaluation (Table 1)4. Laboratory Renal parenchymal disease
evaluation should be preceded by detailed history Renal artery stenosis
and clinical evaluation to get clues on the cause
Endocrine causes
and hence to decide on investigations.
Primary or essential HT
95% of hypertension in children is acute Adolescent hypertension
hypertension, wherein the cause is obvious. In
sustained hypertension, i.e., hypertension Renal parenchymal disease
persisting for more than 6 weeks and/or with Essential hypertension
echocardiographic evidence of left ventricular
hypertrophy, 95% are secondary to an underlying Measurement of blood pressure in all the 4 limbs
renal/extrarenal cause. It is this group which is vital and auscultation for bruit, however
needs evaluation for diagnosis. In the majority obvious the diagnosis may be, should not be
of them, the diagnosis will be obvious with a good ignored.
clinical history and thorough physical Investigations in hypertension1,4,5
examination. More often, investigations are
necessary to confirm the clinical diagnosis and In clinical practice, the following
in only about 5% of patients, investigations are investigations are necessary and more often
necessary for diagnosis itself. Hence, the clinician sufficient to make a diagnosis.
must lay emphasis on proper history elicitation
and complete physical examination which is i. Urine analysis
outside the purview of this review. History should ii. Urine culture (with proper precautions)
include family history of hypertension,
iii. Serum creatinine
cerebrovascular accidents, renal death and sudden
death. Physical examination should include skin iv. Serum electrolytes
changes like caf-au-lait macules, v. Ultrasonogram of abdomen
neurofibromatosis, renal and bladder mass.
vi. Echocardiogram
46

vii. Renal biopsy (in the event of diagnosis of
chronic glomerular disease)
The rest of the investigations discussed
below along with common investigations
mentioned above need the assistance of pediatric
nephrologist.
Urinalysis
Severe proteinuria and hematuria suggests
glomerulonephritis. Hypertension of long
standing nature can produce mild to moderate
proteinuria without hematuria. Low specific
gravity or osmolality may be seen in chronic
tubulointerstitial disease, chronic renal failure,
renal cystic disease and dysplasia. Urinalysis
may be normal in renovascular hypertension.
Transient urinary findings, may make one miss
the diagnosis in PIGN.
Blood count
Microangiopathic hemolytic anemia is a
feature of hemolytic uremic syndrome and
normocytic normochromic anemia is seen in
chronic renal failure.
Routine serum chemistry
Serum creatinine and blood urea estimation
help in identifying renal impairment of renal
parenchymal disease. Elevated blood glucose can
be seen in pheochromocytoma. Serum
cholesterol and triglyceride estimation are
important, as they are cardiovascular risk factors.
Normal serum electrolyte rules out adrenal
hormonal disturbance as a cause for hypertension.
Low serum sodium with elevated potassium
suggests hypoaldosteronism or congenital adrenal
hyperplasia. Hypokalemia, metabolic alkalosis
and high normal serum sodium indicate
hyperaldosteronism. Hyperkalemic metabolic
acidosis is a feature of renal failure.
47
2003; 5(2):135
X-ray chest and abdomen
Cardiomegaly and left ventricular
hypertrophy are the important features of
sustained hypertension. X-ray abdomen may
show features of renal stones and pointers for
metabolic renal bone disease.
Echocardiography
On documentation of sustained hypertension
the child should undergo echocardiography to
assess the end organ effect of hypertension, left
ventricular hypertrophy. Further, coarctation of
aorta as the cause for sustained hypertension can
be identified. Serial echocardiographic
evaluation periodically is mandatory to ascertain
the effect of therapy.
Ultrasonogram of abdomen
This imaging modality is popular for
documenting the renal size, gross anatomy and
intrinsic details of kidney structure. Multiple
communicating cystic structures, large renal
pelvis and visible parenchyma are features of
hydronephrosis. Diffuse echoes or echogenic
mass within the vessels may denote renal artery
or renal vein thrombosis. Reflux nephropathy
shows irregular small kidneys. Chronic
pyelonephritis due to both reflux and non-reflux
causes can show small and irregular kidneys.
Bilateral smooth and small kidneys indicate
chronic glomerulonephritis or renal artery
stenosis, hypoplasia or dysplasia involving both
kidneys. Unilateral small regular kidney indicates
unilateral renal artery stenosis. Infantile
polycystic kidneys are identified by echogenic
enlarged kidneys with small cysts.
Nephromegaly with multiple large cysts denote
autosomal dominant polycystic kidney disease.
Intravenous urogram
This imaging modality is important for
assessing renal size anatomy and function of
Indian Journal of Practical Pediatrics
individual kidneys. A conventional IVU is of little
value and only minute sequence IVU is found
useful in childhood hypertension. In conventional
IVU we take the first picture after the contrast
only at 5th minute. On the contrary if we do
minute sequence (rapid sequence) IVU with
pictures after contrast at 1, 2, 3 and 5 minutes
followed by regular IVU pictures one can
document the ischemia effectively. Distal branch
artery stenosis may not be picked up in IVU. On
documenting ischemia selective renal
angiography can be done using concerned
modalities. Unilateral renal artery stenosis can
be identified by diminished size of the kidney,
delay in appearance of nephrogram and delayed
excretion of the contrast by the ischemic kidney,
the kidney with renal artery stenosis. Apart from
these three major criteria for ischemic kidney
there are many minor criterias. Decrease in the
size of the pelvicalyceal system, ptosis of the
kidney, notching on the ureters due to collaterals
developed following renal ischemia are some of
them.
Apart from renal ischemia, reflux
nephropathy can be documented by abnormal
renal contour and deformed calyx indicative of
renal scars which is also the feature of chronic
pyelonephritis due to non-reflux causes. Opaque
striations running into cortex indicative of
autosomal recessive polycystic kidney disease
and distorted, splayed calyces due to multiple
cysts denoting autosomal polycystic kidney
disease can be noted in IVU.
Voiding cystourethrogram (VCUG)
This important imaging modality is needed
to document posterior urethral valves (PUV) and
vesicoureteric reflux (VUR) without ambiguity.
Reflux nephropathy causing hypertension and
PUV related chronic tubulointerstitial disease are
some of the common causes of hypertension in
children. In conventional VCUG urethral
48
2003; 5(2):136
anatomy is delineated and is useful for PUV
detection. We can also grade the VUR but the
test cannot be repeated frequently, as ionizing
radiation is more. If Dimercapto Succinic Acid
Scan (DMSA) is indicative of pyelonephritis but
voiding cystourethrogram (VCU) failing to show
VUR the child may need direct radionuclide
cystogram (DRNC), which is more sensitive than
VCU to detect VUR. Direct radionuclide
cystogram can be repeated frequently, as ionizing
radiation is less.
Radio nuclide imaging
Radio nuclide scintigraphy may be used to
image genitourinary tract and to examine renal
perfusion and functioning. Radionuclide
scintigraphy uses pharmaceutical compounds that
can assess renal function and anatomy by
measurement of GFR, tubular secretion or tubular
integrity by measurement of isotope retention.
Radionuclide renal scans have greatly reduced
the need for intravenous urogram as an
investigation in childhood hypertension. In this
modality the child is exposed to only a small dose
of ionizing radiation. Information on renal blood
flow and split renal function can be obtained.
Even in children with compromised renal
function this test can be done. This test has
completely replaced the need for IVP in neonates.
IVP in newborns is associated with poor
concentration of the radio-contrast by the
kidneys. But one should note that urinary tract
anatomy is not better described by radionuclide
scan.
In children with renovascular hypertension
the renal radionuclide scan (DTPA) shows
reduction in renal blood flow and GFR on the
affected side in the renogram. On doing captopril
renogram after one hour of challenge dose of
captopril, the reduction in blood flow and GFR
are found accentuated in children with
renovascular hypertension. Bilateral

renovascular disease is difficult to diagnose with
captopril enhanced renal scan as the blood flow
is symmetrically diminished on both sides.
In DTPA the delay in tracer reaching the
collecting system as noted by delayed intrarenal
transit time suggest i) renal insufficiency ii) renal
vein thrombosis iii) pyelonephritis iv) renal artery
stenosis and v)dysplastic kidney. When there is
normal transit time but delay in drainage the likely
possibility could be PUJ obstruction or VUR. In
ureteropelvic junction obstruction delay in
excretion noted in the excretory phase not
abolished by diuretics is indicative of organic
obstruction.
Cortical function defects seen in
pyelonephritis, infarction, scarring and fetal
lobulation are identified by DMSA. Reflux
nephropathy is the common condition associated
with scarring. It also helps in identifying the
cortical function both in acute and chronic
pyenonephritis even in children with renal failure.
Computerised tomography of kidneys
This essential modality of imaging is
very useful in picking up tumours associated with
hypertension and perirenal collections causing
ischemia to the kidney as in Page kidney. The
tumours like neuroblastoma and pheochromo-
cytoma can be identified.
Doppler flow ultrasound
This study is attractive by being non-
invasive but is not sufficiently sensitive to be the
final diagnostic imaging study when renovascular
disease is suspected. Positivity is very useful but
negativity does not rule out renal ischemia.
Increased peak velocity, spectral widening distal
to the stenosis are the features documented in
renal artery stenosis and in renal transplant artery
stenosis.
49
2003; 5(2):137
Selective renal angiography
This study is essential to localize the site of
renovascular disease and to predict the type of
disorder causing the renovascular hypertension.
Fibromuscular dysplasia which is a common
etiology of renovascular hypertension is
characterized by stenotic lesions in the main renal
artery and post-stenotic aneurysmal dilatation.
Beaded appearance in the renal artery is possible
if several segments are involved. In aortoarteritis
the renal arteries are usually involved at the origin
from aorta.
Digital substraction angiography can replace
selective angiography as the radio contrast is
injected intravenously in a large vein and the
arterial phase of renal vasculature is obtained by
digital substraction methodology. This method
needs larger volumes of radio-contrast material
and cooperation of the patient. Because of
smaller sized renal arterial tree, this method is
not fully useful in children.
Classical aortogram done with contrast
followed by selective renal angiography was the
gold standard investigation for renovascular
hypertension in adults. This investigation was
done with great difficulty in children above 5
years of age. The advent of doppler study, CT
angiography and MRI angiography has
revolutionized the investigation for evaluating a
child with renovascular hypertension.
MRI arteriogram
It is useful in the evaluation of renal arterial
vasculature and aorta and to assess the function
of renal hypoperfusion. It helps to identify renal
arterial narrowing due to intraluminal and
extraluminal causes. Advantage of MRI
arteriogram is that contrast needed is much less
and hence less nephrotoxicity. The sensitivity
and specificity is less when compared to CT
angiography.
Indian Journal of Practical Pediatrics
CT angiography
The sensitivity and specificity of this
important imaging modality is 98% and 94%
respectively. It is very safe procedure in children
and is less invasive than digital substraction
angiography.
Renal vein renin assay
This assay is usually done along with renal
angiographic study. Renal vein renin level is 25%
higher than peripheral venous renin level. In
children with unilateral renal or renovascular
disease, renal vein renin levels on the affected
side is exceedingly high. Renal vein renin level
from the diseased side should be above 50% than
renin level of inferior venacava and then only
full benefit will be present after intervention.
Peripheral plasma renin activity
Elevated levels are seen in renovascular
hypertension, renal parenchymal disease and
some of those with essential hypertension. A very
low peripheral plasma renin activity is seen in
mineralocorticoid excess hypertension. Elevated
plasma renin levels is associated with renal artery
stenosis and 21 hydroxylase deficiency. Primary
reninism is caused by renin secreting tumours,
benign or malignant, which can be intrarenal or
extrarenal. All of them have hypokalemia with
elevated plasma renin levels and can be
diagnosed with angiography and CT scan.
Plasma aldosterone
Elevated aldosterone level is associated with
elevated plasma renin in renal artery stenosis. In
hyperaldosteronism, the elevated aldosterone is
noted with normal renin level. Low aldosterone
along with high plasma renin is noted in 21
hydroxylase deficiency. Low aldosterone and
low renin levels are seen in 11 beta hydroxy
steroid dehydrogenase and 11 hydroxylase
deficiencies. Hypoaldosteronism with
50
2003; 5(2):138
hyporeninemia along with hyperkalemic
hypertension, hyperchloremia and normal renal
function may point towards Gordons syndrome.
With hypoaldosteronism with hypokalemic
hypertension one should think of
psuedohyperaldosteronism, Liddles syndrome.
Serum cortisol and 24 hours urine 17 hydroxy
corticosteroid
Elevated free serum cortisol and 24 hours
urinary 17 hydroxy corticosteroids are suggestive
of hypercortisolism. Following dexamethasone
(3.75 mg/m2/day x 2 days) if the level falls it is
suggestive of ACTH induced adrenal hyperplasia
(Cushing disease).
Urinary and plasma catecholamine levels
Elevated plasma epinephrine or
norepinephrine or increased urinary
metanephrine levels suggest pheochromocytoma
and neuroblastoma.
Meta iodo benzyl guanidine (MIBG) scan
It is both sensitive (86%) and specific (95%)
in identification of catecholamine secreting
tumours like pheochromocytoma. A reimaging
after 48 hours of injection of radionuclide
material can also identify extrarenal location.
Approach to investigation in hypertension4,6
Confirm BP on three occasions. If normal
BP is documented (BP < 90th percentile), we
are going to maintain the health surveillance.
If hypertension is confirmed (BP > 95th
percentile) we go to the next stage.
History of drug intake, decongestant nasal
sprays or oral decongestants
(sympathomimetics) for the common cold
and glucocorticoids will give the clue
towards drug induced hypertension. Stop
the drug and reevaluate after adequate
period. If hypertension is resolved, a drug

induced/related hypertension is the diagnosis
made. If hypertension is not resolved, child
needs investigations for other secondary
etiologies. Similar step also should be taken
when there is no history of drug intake in
the hypertensive child.
Documentation of BP in all four limbs is an
important step. Upper extremity
hypertension only, will give us the clue
towards coarctation of aorta. Documentation
of pulses in peripheral, palpable and
accessible blood vessels is mandatory.
Hypertension in all the four limbs will
indicate the need for investigatory approach
for other secondary causes for hypertension.
ECHO evaluation, doppler studies and
aortogram may be needed as per the
diagnosis.
If plasma renin activity is low, one should
consider mineralocorticoid excess. If it is
high one should think of renovascular
etiology (or even renal disease causing
hypertension). Renal ultrasound, captopril
scan, renal vein renin, doppler study and
renal angiography are the investigations
needed in this situation. IVU will give
positive findings of ischemia in the kidney
that has affected blood vessel. But
assessment of plasma renin and renal vein
renin are not routinely available in many
centers. Discrepancy of kidney size by USG
and ischemic changes in the affected kidney
by minute sequence IVU will point towards
renal artery stenosis.
Renal function tests like estimation of blood
urea, serum creatinine and serum electrolytes
are mandatory. If the child has normal renal
function but hypokalemia one should think
of mineralocorticoid excess. Even
renovascular hypertension can have
hypokalemic hypertension. If the child has
abnormal renal function the diagnosis is
51
2003; 5(2):139
essentially renal parenchymal hypertension.
History and clinical examination by this time
also would have pointed towards the etiology
of renal parenchymal disease either
glomerulonephritis or the other group
including chronic pyelonephritis, renal
dysplasia and cystic renal disease.
Investigations needed in glomerulonephritis
are:
24 hours urine protein, creatinine and
creatinine clearance
Serological evidence for infection in acute
HT like ASO
Complements C3, C4 in immune related
hypertension
Serological tests for SLE
Peripheral blood smear for microangiopathy
for acute HT
Renal biopsy in non-contracted kidneys for
confirming the diagnosis of chronic
glomerular disease
Investigations for chronic pyelonephritis,
renal dysplasia and cystic renal disease
include:
Renal ultrasound, Radionuclide renal scan,
DTPA and/or DMSA scans, VCUG in
chronic pyelonephritis
In children showing abnormal urinalysis
(hematuria and/or proteinuria or defective
urinary concentration) renal disease as the
cause of hypertension should be considered
and investigations for glomerulonephritis
and the group of chronic pyelonephrits, renal
dysplasia and cystic renal disease should be
done depending on the presentation of other
features.
A clinical suspicion of pheochromocytoma
should make the clinician do the relevant
Indian Journal of Practical Pediatrics 2003; 5(2):140

investigations. Sustained or labile References

hypertension, poor weight gain, episodes of
shock like features needing intravenous
fluids, excessive appetite, hypertensive crisis
on palpation of abdomen are some of the
features that make one think of
pheochromocytoma. Relevant investigations
include urinary catecholamines and
metabolites, plasma catecholamines,
computerized tomography of the abdomen
and 131I metaiodobenzyl guanidine (MIBG)
scan to confirm the cause of HT.
Conclusion
Hypertension in children is no longer an
uncommon disease. Causes are many.
Hypertension in children should be always
considered secondary unless proved otherwise.
Essential hypertension is also possible in children
and is being increasingly documented in
adolescents. High normal BP of childhood is a
pointer towards adult hypertension. All possible
investigations should be done as per history,
clinical examination and initial laboratory
evaluation before defining hypertension as
essential.
1. Rita D Swinford, Julie R Ingelfinger. Evalua-
tion of hypertension in childhood. In: Pediat-
ric Nephrology, 4th Edn., Eds., Martin Barrat,
Ellis D.Avner, William E. Harman, Lippincott
William & Willkins, Pennsylvania 1999; pp
1007-1037.
2. Kishore Phadke. Investigations in hyperten-
sion in children. In: Pediatric Nephrology, 2nd
Edn, Eds. Nammalwar BR, Vijayakumar M.
Madras, 1991; pp 303-305.
3. Srivastava RN, Bagga A. Hypertension. In:
Pediatric Nephrology, 3rd Edn Eds. Srivastava
RN, Bagga A, JayPee Brothers, New Delhi,
2001; pp 228-242.
4. Kanwal K.Kher. Hypertension. In: Clinical
Pediatric Nephrology, International Edition,
Eds Kanwal K.Kher Sudesh P.Makker,
Mcgraw-Hill Inc. New York 1992; pp 323-375.
5. Pankaj Hari, Rajendra N, Srivastava. Renal
imaging in children with persistent hyperten-
sion. IAP J Pract Pediatr 1996; 4(4): 237-244
6. Vijayakumar M. Investigatory approach to
childhood hypertension. Proceedings of the
CME programme on Pediatric Nephrology-
2002 and beyond of National Academy of
Medical Sciences. 2002; pp 80-82.

NEWS AND NOTES

Lakeside Education Trust, Twenty First Annual CME
Subject: Recent trends in pediatric practice
Date: - Sunday, July 27th, 2003. Venue: Hotel Atria, Bangalore.
For further details contact
Dr. H. Paramesh, Chairman, Lakeside Education Trust,
21st Annual CME Secretariat, Lakeside Medical Center and Hospital
33/4. Meanee Avenue Road, Near Ulsoor Lake, Bangalore - 560 042
Phone: 5303677, 5304276, 5566738, 5366723, 5512934; Fax: 5303677
E-mail: dr_paramesh l@yahoo.com
Co-sponsored by
H.P. Foundation, IAP Karnataka State, IAP - Bangalore Branch (BPS), IMA - Bangalore East Branch
Pediatric Association of Bangalore, Lakeside Medical Center & Hospital,
IAP Environment & Child Health Group, Karnataka Nephrology Transplant Institute
Lakeside Institute of Nursing & Medical Technology

52

LABORATORY MEDICINE
CLINICAL NEUROPHYSIOLOGY
IN PEDIATRIC PRACTICE
* Ayyar SSK
* Suresh Kumar
** Vasanthi D
*** Sangeetha V
The vast advances in medical electronics and
computer technology have made several
sophisticated but essential investigations possible
in the diagnosis, management and prognosis of
neurological disorders.
A well-equipped neurophysiology
laboratory caters to a multitude of test protocols,
the common among them being EEG
(electroencephalography), EMG (electromyo
graphy), NCS (nerve conduction study- motor
and sensory), VEP (visual evoked potentials),
BSEP (Brainstem auditory evoked potentials),
BERA (Brainstem evoked response audiometry),
SSEP (Somatosensory evoked potentials both
neural and dermatomal stimulation), RNS
(Repetitive nerve stimulation study for
myasthenia), Facial nerve and blink reflex studies
and SSR (sympathetic /galvanic skin response).
Such an array of tests demand precise
knowledge of neuroanatomy and
neurophysiology on the part of the technician and
hands-on experience in the performance of the
tests in order to reach a degree of perfection. The
* Consultant in Clinical Neurophysiology
** Senior Neurotechnician
*** Junior Neurotechnician
Neurolaboratory and Epilepsy & Sleep
Disorders Centre, Vijaya Health Centre, 175,
NSK Salai, Vadapalani, Chennai - 600 026
53
2003; 5(2):141
clinical neurophysiologist on the other hand
should have adequate training in the different
modes of testing and the interpretation of the test
results and aid in advancing and clinching the
diagnosis. In short, any neurophysiology test
should be considered as an extension of the
clinical neurological examination.
EEG (Electroencephalography):- Chief role is
in the diagnosis of epilepsy and definition of the
seizure type. Epileptiform discharges are
recorded in about 45-50% cases of epilepsy; with
activation techniques such as hyperventilation,
photic stimulation, sleep deprived and sleep
induced recordings the yield of information can
be increased (Fig 1 and 2). Nevertheless it should
be remembered that a normal EEG does not
exclude epilepsy and diagnosis of epilepsy should
always be clinical at the first instance. Advances
in technology have made it possible to integrate
EEG and video imaging of the patient so that the
epileptic discharge can be synchronized to the
epileptic fit as observed on the video
(synchronized video EEG). Such precise
correlation between the seizure and epileptic
discharge has become mandatory and a prelude
to the consideration of epilepsy surgery.
EMG (Electromyography) uses a needle
electrode inserted into the muscle which records
the electrical potentials generated in the muscle
at rest and during graded muscular contraction.
A comparison is then possible between normal
pattern and values and those obtained in diseases
of the muscle such as muscular dystrophy,
myopathy (congenital, acquired), motor neuron
disease and peripheral nerve diseases. Fig 3 and
4 compare the findings in motor neurone disease
and myopathy.
Indian Journal of Practical Pediatrics 2003; 5(2):142

FP2-A2

F8-A2

T2-A2

T4-A2

T6-A2

O2-A2

Fp1-A1

F7-A1

T1-A1

T3-A1

T5-A1

O1-A1
Fig 1. 3Hz spike and slow wave discharge elicited on hyperventilation in petitmal seizures

F p 2-A 2

F 4-A 2

C 4-A 2

P 4-A 2

O 2-A 2

F p 1-A 1

F 3-A 1

C 3-A 1

P 3-A 1

O 1-A 1

Fig 2: Generalised spike and slow wave complexes frontally predominant in a patient with
generalised tonic clonic seizures
54
 2003; 5(2):143
E M G - LeftA BD D igM inim i E M G - LeftA BD D igM inim i

p o sitive sh a rp w a ve

fib rilla tio n s

100 (V ) 10 (m s 500 (V ) 50 (m s
Fig 3: EMG in motor neurone disease classical findings are fibrillations, positive sharp waves, long
duration high amplitude motor unit potentials, delayed recruitment and reduced interference pattern

E M G - R ightD eltoid E M G - R ightE xtD ig Brev

200 (V ) 10 (m s 200 (V ) 50 (m s

short duration MUPS low amplitude interference pattern

Fig 4: EMG in myopathy: The characteristic finding is motor unit potential (MUP) of short duration
and low amplitude. As all motor neurons are intact the interference pattern is full. The recruitment of
motor units is early in these cases

NCS (Nerve conduction study): The peripheral conduct impulse to the muscles and end organs
nerves for the four limbs and trunk emanate from and the sensory fibres conduct impulse from the
the spinal cord and the cranial nerves from the peripheral sense organs to the central nervous
brainstem. The motor fibres in these nerves system. Nerve conduction study evaluates the

55
Indian Journal of Practical Pediatrics 2003; 5(2):144

conduction of the nerve impulse in terms of
latency (time from stimulus to the onset of
response), velocity of conduction and amplitude
(voltage of the motor or sensory action potentials
generated). The conduction in proximal portions
of the peripheral nerves and roots can be
measured by the late response studies (ie, F wave
and H reflex). NCS is the most common
neurophysiological evaluation in neurological
practice and is useful in a variety of peripheral
nerve disorders such as diabetic neuropathy,
nutritional neuropathy, Guillain Barre Syndrome,
toxic and hereditary neuropathies. (fig 5, 6 & 7)

R ightM edian M otor R ightM edian M otor

P NORM Al HM SN
D L - 2 .5 8 A m p 1 4 . 3 4 m V D L - 6 .5 m s, A m p - 0 .0 6 m V
P L 6 .0 2 C V 5 2 .3 3 M /s P L -1 4 .7 7 , C V 1 3 .3 1 M /s
O W rist P
W rist
R
O TR

T
P
P
Elbow
O
TR

Elbow
O R

2000 (V ) 5 (m s) 50 (V) 5 (m s)
Fig 5: Hereditary Motor Sensory Neuropathy (HMSN) Type 1 in a girl aged 6 yrs; Note
prolonged distal latency, grossly reduced amplitude and grossly decreased motor conduction
velocity. Normal response and values are depicted on the (L) side

R ightPeroneal-F R ightPeroneal-F
NO RM AL
F la te n cy 4 1 -4 6 m s

2000 (V ) /200 (V ) 10 (m s 1000 (V ) /100 (V ) 10 (m s

Fig 6 : Guillain Barre Syndrome (GBS) boy of 16 yrs; the earliest abnormality is
prolongation, absence or infrequency of F wave response and this is the hall mark of GBS in the
typical clinical setting
56
 2003; 5(2):145
LeftTibialH R ightTibialH
H - R e so n se N O R M A L
H - R e sp o n se A B S E N T
M

20000 (V ) /1000 (V ) 10 (m s 500 (V ) /500 (V ) 10 (m s

Fig 7 : H reflex response from a normal subject compared to absent H response in sciatic
nerve injury following gluteal injection in a boy of 6 yrs

EP (Evoked Potential Studies): Advances in
electronic and computer averaging techniques
have made it possible to measure very tiny signals
of the order of microvolts (one millionth of a volt)
from the visual, auditory and somatosensory
pathways in the central nervous system.
Measurement of the artifact-free biological signal
obtained is made in terms of latency (time period
from stimulus to response) and amplitude of the
the retina of the eye to reach the visual area of
the brain concerned with normal perception
(P100 latency). This test is of immense value in
assessing the visual pathways in conditions such
as optic neuropathy (Fig 8), multiple sclerosis,
pituitary and other brain tumours.
VEP
N 75
N 145

signal. Sequential recordings from different 1

1:
2R
levels of the spinal cord (spinal evoked potentials)
makes it possible to assess conduction in N o rm al

segments of the spinal cord and helps in the P 100 R 112 m s 13.6 u v

localization of the spinal lesion. 1:

4L
N 145
N 75
1:
3L
VEP (Visual Evoked Potential): Consists of
presenting a reversing chess board pattern of P 100
O p tic n eu ro p ath y (L )

dark and light stimulus to the eyes from a TV L 138.00 m s 6.8 u v

monitor placed one meter away from the eyes of 25 (m s

the subject and recording the visual response
from the occipital area of the brain through
surface electrodes placed over the scalp at
relevant sites. Normally it takes about 100
milliseconds (1/10 sec) for a light impulse from
57
Fig 8 : Visual Evoked Potential (VEP) :
Normal on the right compared with abnormal
on the left. Note the moderate-to-marked
prolongation of the P100 latency with reduced
amplitude in optic neuropathy (L)
Indian Journal of Practical Pediatrics 2003; 5(2):146

BAEP (Brainstem Auditory Evoked Potential):
In this modality click sounds are presented to each
ear separately at different decibels and rates of
stimulation while blocking the opposite ear with
white noise. Recording is made from an active
electrode placed over the mastoid and referenced
to the vertex with opposite mastoid acting as the
ground. As a standard practice about 2000
averages are made to obtain a artifact-free signal
consisting of five major peaks named waveform
I to V, each waveform representing the generator
of the potential as auditory impulse passes
sequentially along the auditory nerve to the
auditory cortex. Waveforms VI and VII which
are believed to be generated in the auditory cortex
are inconsistent and inconstant and therefore are
not included in the measurement. Latency to
waveform I, III and V and interpeak latencies I-
III, III-V and I-V as well as amplitudes of
waveform I and V are measured. Auditory nerve
function is represented by the latency and
amplitude of waveform I. The interpeak latencies
I-III and III-V give a measure of conduction and
integrity of lower and upper brainstem auditory
pathways respectively. This test is useful in
assessing auditory nerve function in children and
adults and in lesions such as multiple sclerosis
and stroke affecting conduction in the brainstem
auditory pathways.
BERA (Brainstem Evoked Response
Audiometry) is a modification of BAEP test and
is widely used in assessment of auditory function
in high risk neonates suffering / recovered from
hyperbilirubinaemia, hypoxic ischaemic
encephalopathy (Fig 9), meningitis, convulsions
and in preterm low birth weight babies and
children with hearing deficiency.
SSEP (Somatosensory Evoked Potentials): The
sequential conduction of a nerve impulse through
the peripheral nerves (such as the median, ulnar,
tibial and peroneal) to the spinal cord and from
there through the spinal somatosensory pathways,
the brainstem and thalamic pathway to the
cerebral sensory cortex can be recorded and the
latency and response in terms of voltage

BA E P C lick BA E P C lick
V
NO RM AL H IE
IV
III I V 100 dB
80 dB
I II Ia III IV
1:
7R
1:
6R
Ia
1:
1L II
Va
Va 1:
2L
80 dB
1:
2R
1:
1 R
60 dB
1:
3L
4 60 dB
1:
3R
1:
4 R

40 dB
40 dB 1:
8
5R
1: R
5
1:
6L

1 (m s) 1 (m s)
Fig 9: Brainstem Evoked Response Audiometry (BERA): Left Normal response consists of
waveform V elicited at 40 dB and I to V waveforms with normal latency and amplitude
at 80 dB Right waveform V elicited only at 80 dB indicating severe hearing deficit.
This finding is supported by delayed waveform I with very low amplitude of
waveforms I to V

58
 2003; 5(2):147

measured. The peripheral nerve is stimulated and helps to locate lesions in the spinal cord,
recording is made from surface electrodes placed brainstem or cerebral cortex. The test is useful
over the limbs, spine or scalp region overlying in multiple sclerosis, stroke, brainstem lesions,
the sensory cortex. This gives a measure of the spinal cord tumours, transverse myelitis etc.(Fig
sensory conduction in each of the segments and 10, 11)
M edian SE P M edian SE P
N O R M AL C E R V IC A L C O R D C O M P R E S S IO N
N 20
1:C3'
1:C3'-
-Fz
Fz:
:R
R N 20 1:C4'
1:C4'-
-Fz:
Fz:L
L
P 22

N 1 3 -N 2 0 7 .8 6
P 22 m s
N 13
N 13 2:C5s-Fz:L
N 1 3 -N 2 0 6 .1 7 m s2:C5s-Fz:R

E P -N 1 3 4 .6 1 m s
EP E P -N 1 3 4 .5 5 m s EP
3:EPi-Fz:R 3:EPi
3:EPi-
-Fz
Fz:
:L
L

5 (m s) 5 (m s)
Fig 10: Somatosenspry Evoked Potentials (SSEP) from upper limbs (median nerve
stimulation). Recording made from Erbs point, C5 spine and contralateral
scalp area (C4). EP, N13 latency normal but N13-N20 interlatency (normal
upto 7 ms) is prolonged due to cervical cord compression.
TibialSEP TibialSE P 1:
Cz'
-Fz:
L
N 45 NORM AL T ran sverse m yelitis
1:C z'-Fz:R
1:C z'-Fz:R
N 45

P 37
P37

LP

2:T12-Ic:R 2:
T12-
LP
2:T12-Ic:R T12-I
2: c:
c:L
I L

PF
3:PopF-Kn:R PF 3:
PopF-
PopF-Kn
3: Kn:
:L
L

10 (m s 10 (m s
Fig 11 : Somatosensory Evoked Potentials (SSEP) from lower limbs in transverse myelitis
compared to normal. Note the marked prolongation of the P37 latency and decreased amplitude
recorded from the scalp overlying leg area of the cortex. The N22 P37 latency is prolonged (28
ms) in transverse myelitis indicating delayed conduction in spinal somatosensory pathways
(normal 15 ms).
59
Indian Journal of Practical Pediatrics 2003; 5(2):148

An extension of this test is dermatomal SEPs
in which the dermatome is stimulated and the
conduction along the particular root subserving
the dermatome is studied as in cervical or
lumbosacral radiculopathies and brachial
plexopathies in children and adults. Entrapment
of the peripheral nerves such as the lateral femoral
cutaneous nerve of the thigh can be studied by
stimulating the dermatomal area of the nerve and
recording from the scalp. The delay in latency
between normal and affected side clinches the
diagnosis.
Polysomnography (PSG) is a fairly recent
modality of investigation in which overnight
recording (for 8-12 hours) is made of EEG
waveforms, respiratory and cardiac parameters
and any abnormal limb movements during sleep.
The study is useful in obstructive sleep apnoea,
excessive day time sleepiness due to different
causes, narcolepsy (sleep attacks), restless legs
syndrome, sleep walking, sleep talking, nocturnal
seizures, enuresis, sleep terrors etc. Sleep centres
are very few in our country, but is an important
requirement in the comprehensive study of sleep
related medical problem in children.
Bibliography
1. Aminoff, MJ, Electrodiagnosis in Clinical Neu-
rology, Churchill Livingstone , New York,
2000.
2. Misra UK, Kalita J. Clinical Neurophysiology,
BI Churchil Livingstone, New Delhi, 1999.

NEWS AND NOTES

PEDINEUROCON-2003
5th NATIONAL NEUROLOGICAL CONFERENCE &
31st RAJASTHAN STATE IAP CONFERENCE-2003
HOST: RAJASTHAN STATE BRANCH IAP
A three day conference is being organized on 7-9th Nov 2003 at Pink City Jaipur
Highlights: Core group meeting on development of protocols for common pediatric neurological
illnesses.
Workshops on EEG, Neuroimaging, Electromyoneurodiagnosis
Guest orations, Poster presentations, Award papers, Panel discussion
Registration Fee Up to 30 June03 31 Aug03 6 Nov03 Spot
IAP Member Rs 700 Rs 900 Rs 1200 Rs 1500
Non IAP Member Rs 800 Rs1000 Rs 1300 Rs 1600
Assoc. Member Rs 500 Rs 700 Rs 1000 Rs 1500
PG students Rs 500 Rs 700 Rs 1000 Rs 1500
Fee for each one day workshop is Rs 1, 000 BESIDES REGISTRATION
Send your demand drafts in favor of PEDINEUROCON-2003 payable at Jaipur.For
Further details please contact Dr H S Bhasin, Organizing Secretary Pedineurocon-2003
Secretariat: 476A/5 Vyas Marg, Raja Park, Jaipur 304002, Ph 0141- 2621962
Email: pedineurocon2003@hotmail.com

60

NUTRITION
SMART NUTRIENTS AND BRAIN
DEVELOPMENT
* Elizabeth K E
The expression of the genetic potential for
growth and intelligence is the sum total of the
interplay of the genetic/host factors with nutrition
and environment. Brain is the soul of the human
being, the key area concerned with our
intelligence, personality, emotions, well-being,
spirituality and probably our existence. As most
of the brain growth occurs in utero and early
postnatal period, the role of maternal nutrition,
breast-feeding and complementary feeding
cannot be underestimated. The nutrients that help
in the development of brain can be called as
smart nutrients.
The number of neurons is almost fixed by
mid - gestation and it is difficult to malnourish a
foetus during this period. Most of the
malnutrition occurs in the third trimester of
pregnancy. The migration of the neurons to the
respective areas, the connections, the
proliferation of synapses, receptors and dendrites
progress in the perinatal period and early
postnatal period, especially first 2-3 years of life.
These are modifiable to a great extent through
diet, specific nutrients especially micronutrients,
stimulating environment, tender loving care
(TLC), parental interaction and play1,2.
The weight of a baby at birth is 3 kg and is
only 5% of the adult weight, whereas the weight
of the brain is 350 g, almost 25% of that of the
adult brain. The average adult weight is around
* Associate Professor, Department of Pediatrics,
SAT Hospital, Medical College,
Trivandrum, Kerala.
61
2003; 5(2):149
60 kg and brain weight is 1400 g, thus the body
grows 20 times compared to the four fold increase
in brain growth. The interesting point is that most
of the brain growth occurs in the first few years
of life. In the first half of infancy, brain growth
becomes 50%; by 2 years it becomes 80%, 90%
by 5-6 years and almost 95% by 10 years of age.
By 2 years of age, body growth becomes only
20% of that of the adult, but brain growth
becomes almost 80%. Thus it is clear that most
of the brain growth is directly influenced by
breast feeding and complementary feeding. The
human brain consists of 100 billion neurons,
almost 1000 billion glial cells as supporting cells
and their connections.
Two third of the weight of the brain is due
to phospholipids and long chain polyunsaturated
fatty acids (LCP). Breast milk is the best for brain
growth, neuromuscular development and
myelination. Thus milk is now found to be
species specific. Low birth weight premature
babies (LBW) fed on preterm milk secreted by
the mothers are found to have 10 IQ points more
than artificially fed babies3,4. Hence milk is also
baby specific.
The smart nutrients that promote brain
growth are variable and belong to various food
groups. The food that we eat also influence our
memory, concentration, comprehension,
judgment, intellect, mood, emotions etc. There
are over 50 neurotransmitters that are affected
by the food and the micronutrients that we take.
Carbohydrate
Among the carbohydrates, lactose is credited
as a smart nutrient. It promotes the synthesis of
cerebrosides and myelination. It is a prebiotic
Indian Journal of Practical Pediatrics
substance that promotes lactobacilli and thereby
digestion. It also promotes the absorption of
calcium and magnesium. The lactose content of
breast milk is double that of cows milk.
Protein
Sulphur containing amino acids are brain
friendly. Cysteine to methionine conversion is
low in the brain of the infant and so high
cysteine: methionine ratio in breast milk is
advantageous for CNS development. Amino
acids are the main precursors of neurotrans
mitters. High tryptophan to neutral aminoacid
ratio in breast milk is beneficial to the brain.
Tryptophan is the precursor of serotonin.
Serotonin is important for mood and sense of
well-being. Choline, a vital amine, is crucial for
brain development and is the precursor of
acetylcholine, which is important in neurotrans
mission and memory. Serotonin is the feel good
neurotransmitter and acetylcholine is the
memory-boosting chemical. Tyrosine is the
precursor of dopamine and is functional in motor
coordination. Taurine is instrumental in brain
growth and maturation of retina. Taurine is an
important neurotransmitter and neuromodulator
of brain and retina. The low content of aromatic
amino acids like tyrosine and phenylalanine,
which are less utilized by small babies, also seems
to be protective to the brain. Moreover, the amino
acids in trans-form are brain- friendly whereas
those in cis-form as in micro waved formula are
neurotoxic.
Lipids
Over 60% of the brain weight is due to
phospholipids and long chain polyunsaturated
fatty acids. The derived lipids, docosahexaenoic
acid (DHA) and arachidonic acid (ArA) are
essential for brain and neuromuscular
development. ArA is the precursor of
prostaglandin. DHA increases the level of
serotonin and acetylcholine. DHA is derived from
62
2003; 5(2):150
omega 3 fatty acid, linolenic acid and ArA is
derived from omega 6 fatty acid and linoleic acid.
These are 30 times more in breast milk than in
cows milk. Infants are unable to convert the short
chain omega 3 fatty acid, alpha linolenic acid into
DHA. The requirement of DHA is found to be
20 mg/kg/day during brain growth. Fish and fish
oils are important sources of omega3 fatty acids
and DHA. These are seen to maintain integrity
of cell membrane in the brain. Almost half of
the lipid in brain cell membrane is DHA. DHA
is the building block for cell membrane and
synaptic connections. Long chain
polyunsaturated fats (LCP) are being tried in
comorbid conditions like hyperactivity, attention
deficit disorders, dyslexia etc. Ketogenic diet is
considered the final answer in intractable
myoclonic seizures.
Micronutrients
These are the vitamins and minerals that are
required only in small quantities, but serve key
functions in the body and brain. Micronutrients
are cofactors in metabolic pathways and are
essential for production of several enzymes and
brain development 5,6.
Among the B complex factors, B1,B2,B3,
B6, B11 and B12 are important for the synthesis
of various neurotransmitters. Thiamin (B1) is
essential in the function of brain and peripheral
nerves. B1 deficiency decreases the ability to
utilize glucose. Deficiency is also associated with
insomnia, loss of memory, visual acuity,
Wernickes encephalopathy, Korsakoffs
psychosis and absent knee jerk. Dry beriberi is
known to cause neuropathy, aphonia etc.
Riboflavin (B2) deficiency is associated with
neuromotor incoordination, personality changes
and impaired performance in psychomotor tests.
Niacin (B3) deficiency leads to pellagra with
dementia and impaired cognition. Pyridoxine
(B6) is essential for the synthesis of GABA, the

inhibitory neurotransmitter and its deficiency
may cause convulsions and peripheral
neuropathy. B6 deficiency is also associated with
sideroblastic anemia. Folic acid (B11) is essential
for neural tube development and periconceptional
supplementation of folic acid can prevent neural
tube defects. Folic acid deficiency is also
associated with chronic diarrhoea, attention
deficit disorder, stroke and autism. Folic acid
and choline are also important for myelin
synthesis. Cobalamine (B12) deficiency is
associated with subacute combined degeneration
of spinal cord, dementia and probably emotional
instability. B11 and B12 deficiency produce
megaloblastic anaemia. Deficiency of folic acid
(B11), B12, B6 and choline leads to elevated
levels of homocysteine that may result in
thromboembolic episodes and stroke. Vitamin A
is important in integrity of the eyes and vision.
Vitamin C deficiency is attributed to reduced
resistance power, reduced IQ score, altered
behaviour and increased incidence of stroke.
Vitamin E is the potent antioxidant; its deficiency
is concerned with transient ischaemic attacks
(TIA), stroke, oxygen toxicity and probably
Alzheimers disease.
Among the minerals, iodine deficiency is the
prototype of mental deficiency caused by a
nutritional deficiency. Iodine deficiency leads
to reduced physical activity, growth and
development and is referred to as endemic
cretinism. And iodine supplementation leads to
substantial improvement if undertaken early. Iron
deficiency is known to cause irreversible changes
in the growing brain. It results in neuromuscular
incoordination, reduced physical activity,
attention and cognition. It also leads to headache
and lack of concentration and impaired auditory
and visual brain stem evoked potentials.
Cytochrome oxidase in mitochondria is an iron
dependent enzyme and oligodendrocytes require
iron for the synthesis of myelin. Iron deficiency
63
2003; 5(2):151
results in deficiency of dopaminergic D2
receptors leading to reduced dopamine and
thereby relative increase in opiates. This shift is
the cause of reduced learning ability in iron
deficiency. The balance between dopamine and
opiates influences learning ability. When opiates
take the lead, this ability comes down. Iron is
also important in serotonin and GABA levels.
Iron deficiency is also known to make the RBCs
rigid thereby increasing the chance of thrombosis.
Conventionally, polycythemia is said to increase
the incidence of thrombosis and stroke. Increased
iron content is also not desirable. It is connected
to Parkinsons disease in adults and Hallervorden
Spartz disease. Similar to iron, copper is an
important component of cytochrome oxidase and
also another enzyme called super oxide
dismutase. As iron and copper share several
properties copper is aptly called the iron twin.
Both iron and copper deficiency are known to
produce microcytic, hypochromic anaemia.
Copper deficiency leads to Menkes kinky hair
disease and excess is associated with Wilson
disease, Indian Childhood Cirrhosis (ICC) and
probably amyotrophic lateral sclerosis and
dementias like Alzheimers. Aluminium excess
is also suspected in the pathogenesis of
Alzheimers disease. Zinc is the constituent of
about 200 metalloenzymes with high activity in
the brain. Zinc deficiency is associated with
diarrhoea, infertility, growth retardation and
neuropsychological problems. Selenium
deficiency is attributed with anxiety, oxidant
stress, depression, low mood etc. It is a powerful
antioxidant. Chromium deficiency is said to
reduce glucose tolerance. Cobalt is useful in
iodine utilization.
Antioxidants
Brain is the seat of abundant metabolic
activity and hence abundant waste products.
Brain consumes 20-30% of entire energy in spite
of having only 2% of body weight. It utilizes
Indian Journal of Practical Pediatrics
maximum amount of glucose and oxygen. In the
bargain, lot of oxygen free radicals and reactive
oxygen species (ROS) are produced as
byproducts. These bullets attack the cell
membrane, mitochondria and damage even the
DNA. It leads to shrinkage and dissolution of
dendrites and synapses and disrupts the
communication system in the brain. The content
of fat in the brain makes it vulnerable to lipid per
oxidation by these oxidants. Antioxidants, both
endogenous and dietary are the only answer to
this disaster. Beta-carotene, vitamin C, vitamin
E, selenium and other phytonutrients act as
scavengers and antioxidants. Copper, iron,
vitamin B complex factors are functional in the
endogenous antioxidant systems like glutathione
peroxidase, superoxide dismutase, catalases,
ceruloplasmin etc7.
Others
Non-protein nitrogens like urea, amino
acids, peptides, nucleic acids, nucleotides,
choline, creatine, creatinine, uric acid, ammonia,
polyamines, N Acetyl glutamine, N Acetyl
neuraminic acid are bioactive factors. These
are seven times more in breast milk than in cows
milk. The exact role of each of these is under
study. Other bioactive factors in breast milk are
lactoferrin, enzymes, hormones, growth factors,
oligosaccharides, mucins and probiotic factors.
Probiotic factors help in digestion, eg, lactic acid,
lactobacilli, bifidus factor etc. Polyamines like
spermine, spermidine and putrescine promote cell
growth and differentiation. Putrescine is the
precursor of GABA. Epidermal growth factor,
nerve growth factor, betacasomorphin, thyroxine,
growth hormone releasing factor etc play a role
in CNS development. Colostrum is rich in
enzymes like lysozyme, peroxidase, xanthine
oxidase which promote cell maturation. Carnitine
is another substance important in lipid oxidation
and various other functions.
64
2003; 5(2):152
Apart from the specific deficiencies, protein
energy malnutrition (PEM) is known to cause
growth arrest, arrest of milestones, regression of
social smile, inability to explore and master the
environment, irritability and apathy. PEM leads
to functional isolation as in the case of hibernation
adapted by certain animals to tide over adverse
situations. This functional isolation in the child
will evoke less interaction from the mother;
caretakers and peer group, resulting in poor
stimulation, TLC and play.
Fish is aptly called a brain friendly food
second only to breast milk. This is now made
more available through the blue revolution.
Fish and fish oils are the source of the omega3
fatty acids, DHA, iodine, zinc and taurine. The
so called fast food and junk food are called brain
busting food due to the deficiency of protective
factors and the presence of excess omega 6 trans
fatty acids which make the cell membrane of the
brain more rigid and less pliable. The omega 6
to omega 3 fatty acid ratio should be kept <5:1.
Greens are the other sources of omega 3
fatty acids. Green leafy vegetables and green,
yellow orange vegetables and fruits are rich
sources of micronutrients and antioxidants.
These are now more available through the
rainbow revolution.
Breakfast should be considered the brains
food. After 8 hours fast, the body reaches the
lowest or basal levels of nutrients and energy in
the morning and so breakfast is like the petrol
for the vehicle in reserve. Unfortunately and
unknowingly many children skip the breakfast
and start the race for the day. Mothers should
take balanced diet during pregnancy and
lactation. She should deliberately take extra
nutrients for the growth and intelligence of her
baby. No baby should be denied the merits of
breast feeding and optimum complementary
feeding during early part of life.
 2003; 5(2):153

Reference Breast feeding and cognitive development: A

1. Carper J. Your Miracle Brain. Harper Collins
Publishers. New York, 2000; pp10-19.
2. Ludingtone Hoe S, Golant SK. How to have
smart babies? Banton Books, New York, 1985;
pp21-32.
3. Lucas A. Breast milk and subsequent intelli-
gence quotient in children born preterm. Lan-
cet 1992; 339:261-264.
4. Anderson JW, Johnstone BM, Rembely DT.
Meta analysis. Am J Clin Nutr 1999; 7014:525-
535.
5. Petro R Vitamins and IQ. Brit Med J 1991; 302/
6781:906-908.
6. Schoenthaler S. Brains and vitamins. Lancet
1991; 337/8743: 728-729.
7. Elizabeth KE, Micronutrients. In Nutrition and
Child Development,2nd Edition, Paras Publish-
ing, 2002; pp:86-114.

NEWS AND NOTES

Indian Academy of Pediatrics Pediatric Hematology - Oncology Chapter
National Training Project Workshops in
PRACTICAL PEDIATRIC ONCOLOGY - 2003
Two day workshops in practical aspects of pediatric oncology for practising pediatricians, pediatric
surgeons and pediatric postgraduates will be held this year at - Hyderabad, Vadodara, Kolkata, Jaipur &
Bhopal (proposed). Registration is now open on first come and zonal basis. Prior registration approximately
two months before the workshop is mandatory. A reference manual of Practical Pediatric Oncology will be
provided free to the delegates about one month before the workshop. This course will help the delegates to
participate in managed shared care of pediatric cancer. For details contact the national co-ordinator or trhe
respective workshop co-ordinators:
NATIONAL CO-ORDINATOR:
Dr. Bharat R. Agarwal
Head of Department, Division of Pediatric Hematology - Oncology, B.J. Wadia Hospital for Children,
Parel, Mumbai - 400 012. Telefax : 00-91-22-26431902, 26426846 Email: prul@bom5.vsnl.net.in
Workshop at Hyderabad: on 22nd & 23rd August 2003:
D. Raghunadharao, MD DM
Professor and Head, Department of Medical Oncology, Room Number #607, 6th Floor, E Block
Nizams Institute of Medical Sciences, Panjagutta, Hyderabad 500 082. Andhra Pradesh
Tel: 040 23371747, Fax: 040 55669049, Mobile: 040 56871537
Emails: telerama@hd2.dot.net.in and telerama@rediffmail.com
Workshop at Bhopal: dates to be finalised
Dr. Shyam Agarwal
Navodaya Oncological Research Center, 108, Zone II, M.P. Nagar, Near Bhopal Eye Hospital,
Bhopal - 462 011.M.P. Tel. No. Off. 272220-19, Res: 551488, Mobile: 98270-55790
Workshop at Kolkata:
Dr. Ashish Mukhopadhyay
Ideal Tower, Flat 7C & 8, 57, D.H. Road, Kolkata - 700 023. Tel.No.Off. 4567050-59, Res: 4486362
Email: ashism2002@yahoo.co.in / somashis1@rediffmail.com
Workshop at Jaipur: Dr. Rajiv Kumar Bansal, 12, Rathapuri, Sodala, Ajmer Road, Jaipur - 302 006. Rajasthan
Workshop at Vadodara:
Dr. Vibha Naik
Dr. Naik Hospital, Kasar Phadia, Opp.Govt. Press, Kotti, Baroda, Gujarat, Tel.No. 0265-2412311, 2434788
Res: 0265-2392149, 2393538, Mobile 98250-29085

65
Indian Journal of Practical Pediatrics
IJPP-IAP CME
RECOGNITION OF A CRITICALLY
ILL CHILD
* Ramachandran P
How to identify a critically ill child?
What are the predisposing conditions?
What is the initial management of critically
ill child?
Critically ill child means a child who is in
a clinical state which may result in respiratory or
cardiac arrest or severe neurologic complication,
if not recognised and treated promptly. This term
does not refer to any particular disease, but many
diseases can lead onto critically ill state.
Whether a child presents with a primary
cardiovascular, respiratory, neurologic, infectious
or metabolic disorder, the goal is early
recognition of respiratory and circulatory
insufficiency. In clinical practice, there are three
common situations that characterise a critically
ill child:
1. Respiratory distress
2. Shock
3. Altered sensorium .
Early intervention is geared towards
preventing the progression of hypoxemia and
hypoperfusion to full cardiorespiratory arrest.
It is easy to recognise a critically ill child
when there is an obvious problem like severe
trauma or unconsciousness. On the other hand it
* Asst. Prof. of Pediatrics,
Pediatric Intensive Care Unit,
Institute of Child Health and Hospital for
Children, Chennai - 8.
66
2003; 5(2):154
is important to identify a child with physiological
derangement in its early stages when signs are
subtle. The golden hour concept applies to all
children with illnesses presenting as emergency.
Early recognition of a critically ill child requires
a systematic and rapid clinical assessment with a
background knowledge of age appropriate
physical signs.
There are many methods to assess an acutely
ill child. A very simple and quick way of
assessment of overall illness and injury severity
is by:
1. Appearance of the child
2. Breathing
3. Circulatory status
These three parameters comprise Pediatric
assessment triangle
Appearance
Breathing Circulation
Appearance of the child
Appearance basically denotes the
neurological status. It is determined by the
oxygen and blood supply to the brain which are
dependent on cardiopulmonary status and the
structural integrity of the brain. The parameters
assessed in appearance are alertness,
distractibility or consolability, eye contact, speech
or cry, motor activity and color of the skin. In
addition, seizures, abnormal posturing, muscle
tone and pupillary reaction are noted.

1. Alertness: Normal children exhibit
awareness and interest in surroundings.
Determine if the child is confused, irritable,
lethargic or totally unaware of environment.
Changes in level of conscious can also be
rapidly assessed by AVPU method.
Awake
Responsive to voice
Responsive to pain
Unresponsive
2. Distractibility or consolability by parent is a
normal phenomenon in infants and young
children.
3. Eye contact with parents or physician is
noted normally at 2 months of age. Failure
to do this, is an early ominous sign of cortical
hypoperfusion and brain dysfunction.
4. Speech / cry: Whether the cry is normal or
whimpering or moaning or high pitched
5. Motor activity: Normal movements of limb,
trunk and neck.
6. Colour of the skin: denotes respiratory and
circulatory status. Skin of palm and fingers
may be pink (normal), pale, cyanosed,
mottled or ashen grey.
Other features in appearance are:
Seizure activity: Seizures with altered
sensorium is a critically ill state as it may lead
onto cardiorespiratory compromise or neurologic
sequalae if not treated.
Posturing: Intermittent flexor (decorticate)
or extensor (decerebrate) posturing occur with
prolonged cerebral hypoperfusion.
Muscle tone: Hypotonic limp child is a bad
sign.
Pupil size: Pupils may be small but reactive
in cerebral hypoperfusion. Unequal pupils is a
medical emergency; may indicate ICP.
67
2003; 5(2):155
Breathing
1. Respiratory rate: Tachypnoea is an early sign
of respiratory distress. Tachypnoea without
increased work of breathing (Quiet
tachypnoea) is seen in shock, heart disease
and acidosis. A slow or irregular respiratory
rate in an acutely ill child is ominous.
2. Work of breathing: Increased work of
breathing (IWB) indicates respiratory
distress or potential respiratory failure. IWB
is assessed by nasal flaring, grunting,
intercostal, subcostal and suprasternal
retractions. Head bobbing and see saw
respirations (severe chest retraction with
abdominal distension) are more advanced
signs of respiratory distress and impending
respiratory failure.
3. Air entry: Effective tidal volume is assessed
by chest expansion and auscultation of breath
sounds.
4. Pulse oximetry: Oxygen saturation
assessment is an important adjunct to identify
oxygenation state in acutely ill child.
Circulatory Status
Circulation is assessed to find out if the
cardiac output meets the tissue demand. Shock
is defined as circulatory dysfunction in which
there is inadequate delivery of oxygen and
substrates to meet the metabolic demands of
tissues. Circulatory status is assessed by heart
rate, skin perfusion, systemic perfusion and blood
pressure.
1. Heart rate: Tachycardia is a common
response to a variety of stresses including
shock. Hence its presence mandates further
evaluation. Bradycardia in a critically ill
child is ominous
2. Pulses: Comparison of central (femoral,
carotid and brachial) and peripheral (radial,
Indian Journal of Practical Pediatrics 2003; 5(2):156

dorsalis pedis and posterior tibial) pulse
volume. In early shock peripheral pulses are
weak. Loss of central pulse is a premorbid
sign and is to be treated as cardiac arrest.
3. Skin perfusion
a. Temperature: When ambient
temperature is warm, hands and feet
should be warm. Hands and feet
become cold when cardiac output falls.
b. Colour: Normally the colour is pink
over the palms upto the fingers. Pallor
or cyanosis or mottling denote
decreased perfusion.
Based on the appearance, breathing and
circulatory status, physiologic status of a critically
ill child is characterised as:
1. Stable
2. Respiratory distress characterised by IWB
3. Respiratory failure characterised by
cyanosis, altered sensorium, poor muscle
tone and poor respiratory efforts.
4. Early shock Peripheral signs with normal
BP
5. Decompensated shock Peripheral signs
with brain dysfunction and hypotension

c. Capillary refill time (CRT): Normal is 6. Cardiorespiratory failure Shock +

less than 2 seconds. Delayed CRT is respiratory failure
again a feature of early shock. Conditions characterising a critically ill child
requiring rapid cardio pulmonary assessment
4. Organ perfusion
1. Tachypnoea Respiratory rate > 60 in
a. Brain perfusion: Brain perfusion can be
newborn
assessed by features already described
in appearance i.e. changes in level of > 50 in infants
consciousness, pupil size, muscle tone > 40 in 1-5 years
and posturing.
2. Bradycardia or Tachycardia
b. Renal perfusion: Urine output may not
Newborn < 80 and > 200
be useful in initial assessment in a
critically ill child, but is useful in 1 month - 8 years <80 and > 180
monitoring the child and evaluation of > 8 years <60 and > 160
renal perfusion. 1-2 ml/kg/hour of
3. IWB and decreased tidal volume
urine output is normal
4. Cyanosis
5. Blood pressure: Shock can be present with
normal, increased or decreased blood 5. Altered level of consciousness
pressure. In early compensated shock, BP 6. Seizures
is normal. In late or decompensated shock
7. Fever with bleeding
there is hypotension.
8. Fever > 41C in less then 3 months or fever
Lower limit (5 th percentile) of Blood in immuno compromised child.
pressure
9. Trauma
Newborn 60 mm Hg systolic
Upto 1 year 70 mm Hg systolic 10. Burns totaling > 10% body surface area
2 years and above 70 + (2 x Age in years) 11. G1 bleeding
mm Hg 12. Poisoning
68

Initial Management of a critically ill child
When a child is assessed to be critically ill,
initial management comprises of taking care of
airway, breathing and circulation. Recognition
of acuity of illness determines the urgency of
intervention. Aggression in response is driven
by degree of physiologic compromise.
1. Airway is kept patent if necessary by
positioning, suctioning and intubation.
2. Breathing: In respiratory distress with
increased WOB, only supplemental O2 is
given in a nonthreatening manner.
If respiratory failure is present, ventilation
is done with maximal supplementary
oxygen.
3. Vascular access and volume expansion with
isotonic fluids such as RL or NS.
4. Avoid oral feeds in a critically ill child.
5. If partial airway obstruction is suspected,
allow the child to assume position of comfort
and avoid any painful procedure.
6. If child presents with seizures, take care of
airway and breathing and control seizures
with IV diazepam or lorazepam. In office
practice, IM midazolam 0.15 mg/kg is safe,
effective and fast.
7. In polytrauma or head trauma open and
maintain airway with cervical spine
stabilisation carry out volume expansion
with early administration of blood and
control bleeding.
8. In acute severe asthma, nebulisation with
salbutamol and if necessary ipratropium.
9. Plan for transport to a centre where child can
be managed further.
69
2003; 5(2):157
Common predisposing factors for a child
becoming critically ill:
1. Age: Younger the age, more the risk
2. Malnutrition / impaired immune status
3. Underlying anatomic / functional defect
4. Nature of illness
5. Bad child rearing / traditional practices
6. Type of medical care received
7. Parents knowledge / awareness
Preparedness to manage critically ill child
1. Oxygen source
2. Oxygen delivery system -
Oxygen mask, (infant, child size)
- Nasal cannula
3. Suction apparatus / suction catheters / mucus
sucker (De Lee)
4. IV cannula 20, 22, 24 size
Scalp vein needles 21, 22, 23, 24 size
5. Intraosseous needles 15 and 18 G
6. Fluids: Normal saline, lactated Ringer, 25%
Dextrose
7. IV sets
8. Self inflating bag (500 ml, 750 ml), valve,
mask with O2 reservoir
9. Drugs: Diazepam, Lorazepam,
Hydrocortisone, Dexamethasone,
Inj Adrenaline 1:1000, Midazolam injections
10. Nebuliser solution: Salbutamol, Ipratropium
11. Laryngoscope, blades
12. Spine board
13. Drug dosage chart
Indian Journal of Practical Pediatrics 2003; 5(2):158

Dos and donts in management of critically ill Donts

child
Dos
1. Be aware of age specific emergencies
2. Know about current epidemic in your area
3. Keep emergency drugs ready and
resuscitation equipment in good condition
4. List the nearest hospital for referral,
telephone numbers of hospitals and
ambulance
5. Inform parents about the problem and what
is being done
1. Dont fail to monitor periodically
2. Dont give only IV fluids without taking care
of airway and breathing
3. Dont give drugs by inappropriate route
4. Dont panic.
Suggested reading
1. Pediatric Advanced Life Support Guidelines
1997
American Heart Association and American
Academy of Pediatrics.
2. Pediatric Emergency Medicine Course guide-
lines, Chennai 2001.
3. Pediatric Critical Care, 2nd Edn., Eds Fuhrman
BP, Zimmerman JJ, St.Louis, Mosby 1998

NEWS AND NOTES

VII RAJNEOCON - 2003 - KOTA

Date : 20-221, September, 2003
Host : IAP Hadoti Branch Kota & NNF Raj State Chapter
The IAP Hadoti branch is organising VII Rajasthan Neonatology Conference on 20-21st September, 2003. at IMA
House, M/B.S. Hospital Campus, Nayapra, Kota. The theme is Better-Newborn care- Need of the Millenium.
Highlights : Faculty includes eminent neonatologists and intensivists of India.
Programme : Common neonatal problems with practical approach protocols and recent advances in form of guest
lectures, Panel discussion and NALS workshop.
Topics : Persistent hyperbilirubinemia. Newer guidelines on neonatal resuscitation, Mec asp. Syndrome-newer
management stratigies, neonatal sepsis, Neuroprotection in HTE, refractory neonatal sizures and fluid-electrolyte
balance in NICU etc.
Registration fee upto 31-08-03 from 1-9-03 Spot
IAP/NNF member 300 400 500
Non member 400 500 600
Accompanying member 200 300 400
NALS workshop 400 500
(Payment through, demand draft only in favour of VII Rajneocon, 2003 Kota)
Correspondence :
Dr. C.B. Das Gupta, Organising Chairperson, 1, Gulab Bari, Arya Samaj Road, Kota - 324 006.
Phone : 0744-2381723, 2322703 Email - ekatmgupta@yahoo.co.in
Dr. Ashok Sharda, Organising Secretary, Sharda Children Hospital, 4-B-14, Talwandi, Kota - 324 005.
Phone : 0744-2428393, 2420066(H), 2426088(R) Email - shardachildhosp@rediffmail.com

70
 2003; 5(2):159

RADIOLOGIST TALKS TO YOU

OBSTRUCTION IN URINARY Sometimes you may see the dilated upper

TRACT
* Vijayalakshmi G
* Natarajan B
** Ramalingam A
In this issue we will discuss problems
pertaining to dialatation of the urinary collecting
system. Dilatation of the collecting system
usually means a block somewhere along the
pathway of flow. This basic inference solves
many clinical problems like urinary tract
infection, a palpable kidney or colic. The
commonest obstruction that is now increasingly
been diagnosed because of the widespread use
of antenatal ultrasound is pelvi-ureteric junction
obstruction.
Fig 1 Shows a dilated pelvicalyceal system
(PCS) consisting of round, black or cystic pelvis
and calyces. The ureter is not dilated. So it tells
you the level of obstruction is at the PUJ. Now
look at Fig 2. Is this a dilated pelvicalyceal
system? Here also you see a number of cystic
spaces like the dilated calyces of a hydronephrotic
kidney. But this is a multicystic kidney. In this
condition the kidney shows a number of cysts.
Unlike PUJ obstruction these do not
communicate with each other. In PUJ obstruction
there is a central large, cystic pelvis and
peripherally situated smaller calyces which all
communicate with the pelvis.
* Asst. Professor in Radiology
** Addl. Professor in Radiology
Department of Radiology
Institute of Child Health & Hospital for Children,
Egmore, Chennai.
moiety in a duplex system as in Fig 3. When
you see double moiety, look for associated
abnormalities of ureters like a ureterocele or
ectopic ureter. If the ureter is also dilated then
one should expect a block at the appropriate level.
Fig 4 shows a ureter that is dilated. Look for the
cause. The commonest is a calculus. Sometimes
the dilation may extend upto the vesico-ureteric
junction. This happens in conditions like a
ureterocele or primary megaureter. The
ureterocele is seen as a rounded, smooth, black
structure projecting into the bladder (Fig. 5).
In primary megaureter the distal part of the
ureter is very narrow and shows frequent
peristalsis. The diagnosis is confirmed with IVU.
All structural abnormalities need to be subjected
to IVU before surgery. If there is bilateral
ureterohydronephrosis it is rightly lower urinary
tract obstruction. The important condition that
one has to be alert to is the posterior urethral
valves. In this the posterior urethra is dilated
(Fig. 6).
This structure can be imaged from the
transabdominal position and perineal route. A
large ureterocele, a vesical diverticulum or a
presacral mass can cause bladder outlet
obstruction as also, a urethral calculus. So you
see that ultrasound is the first investigation in
suspected urinary tract obstruction.

71
Indian Journal of Practical Pediatrics 2003; 5(2):160

Fig 1. PUJ obstruction

Fig 2. Multicystic kidney

72
 2003; 5(2):161

Fig 3. Double moiety U- dilated upper moiety L lower

Fig 4. Dilated PCS and ureter (RU)

73
Indian Journal of Practical Pediatrics 2003; 5(2):162

Fig 5. Ureterocele

Fig 6. PUV
74

CASE STUDY
DENGUE HAEMORRHAGIC
FEVER IN A BOY WITH BOMBAY
BLOOD GROUP A RARE
COINCIDENCE
*Janani Shankar
**Adhisivam B
Dengue fever is an acute febrile viral disease
frequently presenting with headache, bone or
joint and muscular pains, rash and leucopenia as
symptoms. Dengue haemorrhagic fever is
characterized by four major clinical
manifestations : high grade fever, haemorrhagic
phenomena, often with hepatomegaly and in
severe cases, signs of circulatory failure1. Some
of these children with significant clinical bleeding
may require transfusion of blood or blood
products as an emergency. Sometimes a pre-
existing condition of the child may interfere with
the management of the current problem. We
present here one such child with Bombay blood
group who developed dengue haemorrhagic fever
a rare coincidence not reported in literature so
far.
Case report
A four year old boy from Chennai born to
non consanguinous parents was brought to the
emergency room with history of high grade
continuous fever with severe myalgia for two
days following which he started passing black
* Senior Consultant,
** PG Student,
Kanchi Kamakoti CHILDS Trust Hospital,
Nungambakkam, Chennai.
75
2003; 5(2):163
tarry stools and then developed drowsiness and
cold extremities. On examination, he was in
shock as evidenced by absent peripheral pulses,
cold and clammy skin, unrecordable BP, and a
prolonged capillary refill time. Liver was
enlarged 4 cm below the right costal margin.
Melena was the only bleeding manifestation.
Examination of the other systems was normal.
A diagnosis of dengue shock syndrome was made
and he was immediately given appropriate IV
fluids and oxygen by mask.
His lab investigations revealed
thrombocytopenia (Platelet 45,000 / cu.mm),
hemoconcentration (PCV : 42%), raised liver
enzymes (SGOT : 524 IU/L, SGPT : 304 IU/L),
prolonged APTT and serology for dengue both
IgM and IgG were positive. Even with the use
of adequate volume crystalloids for 3 hours, he
was still in shock and was losing excessive blood
from the body in the form of melena. Hence it
was decided to transfuse him with fresh whole
blood and a blood sample for cross matching was
sent.
In the blood bank, a forward typing showed
the blood group as O. However there was no
agglutination with anti H serum and a back
typing confirmed the blood group to be of the
Bombay phenotype (Oh). Being a rare blood
group, finding a suitable donor was very difficult.
Fortunately, a close relative of the boy was
identified to have Bombay blood group and his
blood was transfused to the patient with no
reactions. After the transfusion he improved
hemodynamically and was discharged after a
week of hospitalization.
Indian Journal of Practical Pediatrics
Discussion
The Bombay phenotype (Oh) is a rare blood
group. Though it was first reported by Dr.Bhende
and Bhatia from Bombay in 1952, it is also found
in Caucasians. In India, it occurs with a frequency
of 1 in 7,600 and a high level of consanguinity
has been observed among the parents of Bombay
phenotype. The cause of this group is
predominantly a mutation in the H gene on
chromosome 19 that causes a non functional H
glycosyl transferase. Individuals with this group
fail to express A, B or H antigens on their red
cells or other tissues and hence no agglutination
is noted with anti A, anti B and anti H typing
sera. These individuals have all three antibodies
anti A, anti B and anti H in their serum 2. though
in front typing they appear as O blood group,
the presence of anti H in their serum (a potent
hemolysin of H positive red cells) makes their
blood incompatible with O blood group
individuals. Hence a patient with Bombay blood
group should be transfused only with the same
blood group 3.
Blood grouping should be done routinely by
both front typing (cell grouping) and back typing
(serum typing). The serum grouping serves as a
recheck for the front typing, as proper ABO
grouping is vital in the prevention of disastrous
hemolytic transfusion reactions. It is also
important to use Anti H lectin in front typing of
blood for the presence of H antigen in cells giving
the reaction of O group. Usage of Anti H lectin
in front typing and meticulous back typing with
known A,B,O cells and serum of the individual
is the only way in which patients or potential
blood donors with Bombay blood group (Oh) can
be identified. Sadly, this is not done routinely in
many laboratories.
The implications are
1. Hemolytic transfusion reactions due to
transfusion of normal O group (with H
76
2003; 5(2):164
antigen) blood to Bombay group (without H
antigen) may occur, as the Anti H in the Oh
individuals is a very potent hemolysin. This
will occur especially in situations in which
blood is issued without crossmatching, as in
emergencies.
2. The exact incidence of the Bombay blood
group which is more prevalent in India will
not be known and hence availability of blood
donors of this rare group may not be
identified. In our hospital which is an
exclusive pediatric hospital, over the past
five years we have had three Bombay groups
out of about 18,000 blood groupings done
for patients and two Bombay group donors
out of 4,500 blood donors.
In the above case, had the agglutination test
not been done with anti H and the back typing
the patients blood would have been mistaken for
O group and transfusion with that group could
have been disastrous.
Acknowledgement
We herewith acknowledge the work of all
blood bank technicians of Kanchi Kamakoti
CHILDS Trust Hospital and the kind donor
without whose blood we would have lost the
patient.
References
1. WHO manual Dengue haemorrhagic fever
diagnosis, treatment, prevention and control
2nd edn. Published by Ashok Ghose, Prentace
Hall of India, New Delhi,1997, p1.
2. Frances K Widmann, Technical manual of the
American Association of Blood Banks, 9th edn.
published by American association of Blood
banks, Arlington,Virginia, 1985, pp 177-120.
3. Mollison PL, Engelfriet CP, Marcela
Contreras. Blood transfusion in clinical medi-
cine 9th edn.1993, p154.

CASE STUDY
CAFFEYS DISEASE (INFANTILE
CORTICAL HYPEROSTOSIS)
* Mohammed Thamby
* Nagarajan M
** Ram Saravanan R
Caffeys disease is a very rare pediatric
orthopedic problem of infantile age group. It is
spontaneous, self-limiting and with no definite
etiology. It has no sex or racial predilection.
Report
A female child, third of three siblings,
presented at 2 months of age with swelling and
discolouration of skin of short duration (few days)
over the upper half of left tibial region. The child
was reluctant to move the limb and there was
tenderness on palpation. The child was highly
irritable with mild to moderate fever and other
systems were normal. The child had absolutely
normal birth history and no trauma since birth.
Other siblings were normal.
Blood counts of the child showed, elevated
TC (22500 cells / cu.mm ), elevated ESR ( hour
- 55mm, 1 hour - 97mm), positive CRP (6 mg/L)
and negative VDRL test. Radiological
investigations revealed abnormal cortical
thickening confined to diaphysis of tibia in the
upper part with coarse elevated periosteum.
USG - reported periosteal thickening. CT Scan
showed abnormal periosteal elevation.
* Senior consultants
** Junior Resident in Pediatrics
Child Care Centre, Tirunelveli
77
2003; 5(2):165
Based on the above picture the child was
diagnosed as having acute osteomyelitis and
was treated for around 1 month period, but there
was no response. The child developed same type
of swelling with discolouration over both sides
of cheeks. Radiology also revealed the same
features over the mandibles. It made the
pediatricians to suspect the diagnosis of Caffeys
disease.
DISCUSSION
In this type of clinical presentations,
infantile cortical hyperostosis is usually kept
last in the list of differential diagnosis like acute
osteomyelitis, hypervitaminosis A, scurvy,
syphilis and trauma, since it is rare and all other
conditions need immediate intervention. In acute
osteomyelitis radiological changes occur only if
they are left untreated for 2-3 weeks and it usually
involves the medullary cavity first, then
progresses to the cortex and periosteum ,whereas
in Caffeys disease the pattern of involvement is
reverse.
Infantile cortical hyperostosis is a self-
limiting disease of early infancy, characterised
by swelling of soft tissue, cortical thickening of
underlying bone and hyperirritability.It has no
definite etiology. Inherited defect of the arterioles
of the periosteum, allergy and infective theories
have been postulated in the cousation of caffeys
disease.
Usual age of onset is ninth week of postnatal
life, but cases have been reported even at birth
and as early as twenty fourth week of intra uterine
life. It starts with sudden swelling which is deep
and firm with mild to moderate fever and
Indian Journal of Practical Pediatrics
Fig 1 and Fig 2. Radiogram shows marked involvement of tibia with cortical hyperostosis and
deep soft-tissue swelling.
Fig 3. Arrowmark of the Radiogram shows
involvement of mandible both sides.
hyperirritability; commonly involves mandible
and then ulna, tibia, clavicle, scapula and ribs
are involved. Neither phalanges nor vertebrae
are involved which differentiates it from
hypervitaminosis A.
X-ray usually shows periosteal hyperostosis
confined to diaphysis of long bones. In due course
it becomes homogenous with the underlying
cortex(Fig 1,Fig 2,Fig 3 & Fig 4). It takes several
months and even a year to resolve. Laboratory
values like elevated ESR, elevated alkaline
78
2003; 5(2):166
Fig 4. Arrowmark of the CT scan picture of
leg shows marked involvement of tibia with
cortical hyperostosis.
phosphatase and positive CRP test have been
reported. Sometimes child may report with
anemia. But culture will not grow any infectious
agent.
There is no specific treatment, complete
resolution in 6 9 months is the rule.
Spontaneous remission and exacerbation may
occur. Corticosteroids are effective in alleviating
acute symptoms but has no role on reverting bony
changes.
 2003; 5(2):167

CASE STUDY

NEUROFIBROMATOSIS TYPE I with no signs of union along with sclerosis and

WITH CONGENITAL obliteration of medullary cavity. Orthopaedic
PSEUDOARTHROSIS AND consultation confirmed that this was the typical
presentation of congenital pseudoarthorosis.
HOLOPROSENCEPHALY
There was no positive family history.
*Preetha Prasannan Since admission, the infant was getting
**Veerendra Kumar myoclonic seizures of increasing severity. EEG
***Jayakumar showed a hypsrrhythmia pattern and CT scan
***Sukumaran TU revealed holoprosencephaly. The infant was put
Neurofibromatosis type I (NF-I) is a neuro on temporary bracing of the leg to prevent further
cutaneous syndrome with diagnostic criteria displacement of ununited fracture segments and
including distinct cutaneous and osseous lesions1. is awaiting corrective surgery. Seizures were
This includes congenital pseudoarthrosis of tibia, controlled with high doses of sodium valproate
a rare anomaly with incidence of one per two and prednisolone.
lakh live births2 and which when present is a Discussion
strong pointer to NFI. Here we present an infant
Neurofibromatosis type I (Von
with NFI with congenital pseudoarthrosis who
Recklinghausen disease) is an autosomal
on further evaluation had a developemental
dominant disorder which results from an
malformation of brain, holoprosencephaly.
abnormality of neural crest differentiation and
A five month old female baby presented with migration during early stages of embryogenesis.
multiple caf au lait spots, more than six in
number with greatest transverse diameter more
than five millimeters. She also had a swelling in
lower end of right leg noticed since three
months.On examination, there was anterolateral
bowing of lower leg with abnormal mobility,
simulating a joint, being elicited at the junction
of middle and distal thirds of tibia and fibula.
X-rays taken three months back and presently
on admission revealed a fracture at the junction
of middle and distal thirds of tibia and fibula,

* PG Student
** Lecturer
*** Assistant Professor
Institute of Child Health,Medical College, Fig. 1. Neurofibromatosis type I with cafe-au-
Kottayam, Kerala. lait spots and congenital pseuarthrosis MBIA
79
Indian Journal of Practical Pediatrics 2003; 5(2):168

First clinical and pathological account of the

disease was given by Von Recklinghausen in
1882. Tilesius gave the first description of a
patient with multiple fibrous skin tumors in 1793.
Incidence is 1/4000 and is diagnosed if two out
of the following are present1.
1. Six or more caf au lait spots of more than 5
mm. transverse diameter which may be
present at birth. They are present in almost
100% of NF- I.
2. Axillary or inguinal freckling manifest
around puberty.
3. Two or more Lisch nodules - These iris
hamartomas increase with age, incidence Fig. 2. Neurofibromatosis type II with cafe-
being 5% below three years to 100% above au-lait spots and congenital pseuarthrosis
21 years. MBIA
4. Two or more neurofibromas or one
plexiform neuro fibromatosis. Neurofibro-
mas are small rubbery lesions which appear
around adolescence. Plexiform neuro
fibromatosis involves diffuse thickening of
nerve trunks which may produce overgrowth
and deformity of an extremity. This may be
present at birth.
5. A distinct osseous lesion such as sphenoid
dysplasia or congenital pseudoarthrosis tibia.
6. Optic nerve gliomas in around 15% which
give rise to an afferent pupillary defect. Fig. 3. Pseudoarthrosis R Tibia and Fibula
7. A first degree relative with NF-I. 50% of inneurofibromatosis
NF- I are inherited, rest result from sporadic
mutations. constriction of tibia present at birth. Spontaneous
As 2 out of 7 diagnostic criteria are satisfied fracture or fracture following minor trauma
in this baby, a diagnosis of NF I was made. occurs before two years. In the other types, there
Congenital pseudoarthrosis of tibia, is a may be a congenital cyst, sclerotic segment,
specific type of nonunion, that at birth may be dysplasia or intra-osseous neuro fibroma which
present or incipient. Incidence is one in two lakh fractures and heals poorly. Treatment consists of
live births2. Cause is unknown, but occurs almost early bone grafting and intra-medullary fixation.
always with NF-I, the favoured site being distal Congenital pseudoarthrosis responds poorly to
third of tibia and fibula. Boyds classification treatment with multiple failed surgical procedures
includes six types, the commonest being type and repeated fractures which may necessitate
II which is due to anterior bowing and hourglass amputation.

80

Fig. 4. Congenital Pseudoarthrosis R Tibia
and Fibula
NF I patients are susceptible to
neurological complications including neuronal
migration disorders and cerebral heterotopias.
Various brain tumours including astrocytomas,
meningiomas, optic gliomas, schwannomas and
cerebral vessel thrombosis, stenosis and
hydrocephalus have been described.
This infant had seizures with
holoprosencephaly being detected on CT scan
brain. It is a developemental defect of brain which
results from defective cleavage of the
prosencephalon 3,4. It is characterized by a
globular brain with absence of inter hemispheric
fissure, absent falx, fused ventricles, fused basal
ganglia. Incidence ranges from 1/5000 to 1/
16000. Cause is unknown in majority of cases,
with certain chromosomal aberrations accounting
for a minority. Affected infants die during
infancy.
As there is no definite treatment for NF,
supportive treatment in the form of correction of
pseudoarthrosis and control of seizures can be
offered to this infant5. But the ultimate prognosis
appears grim due to the associated brain anomaly.
81
2003; 5(2):169
Fig. 5. Holoprosencephaly in neurofibro-
matosis I
References
1. Robert HA, Haslam. Neuro cutaneous syn-
dromes, In:Nelson Text Book of Pediatrics, 16th
edn, eds, Behrman, Kleigman, Jenson, WB
Saunders company, Philadelphia, 2000; pp
1835 1836.
2. James H, Beaty. Congenital anomalies of lower
extremity. In: Campbells operative ortho-
paedics-Volume-I, 9th edn, eds S. Terry Canale,
Mosby - A Times Mirror Company, St. Louis
Missouri, 1998; pp 957-961.
3. Bruce O, Berg. Neuro cutaneous syndromes -
phakamatoses and allied conditions. In: Pedi-
atric Neurology - Principles and Practice (Ken-
neth F Swaiman) 3rd Edn volume I, eds, Ken-
neth F, Swaiman, Stephen Ashwal, Mosby, St.
Louis, Missouri, 1999; pp 530-533.
4. Stephen Ashwal. Congenital structural defects.
In: Pediatric Neurology - Principles and Prac-
tice ( Kenneth F Swaiman) 3rd Edn volume I,
eds Kenneth F, Swaiman, Stephen Ashwal -
Mosby, St. Louis, Missouri,1999; pp 251-254.
5. Srikant Basu and Rasmi Sarkar. Neuro fibro-
matosis type I in a family. Images in clinical
practice. Indian Pediatrics, 2001;38(6): pp
670.
Indian Journal of Practical Pediatrics
GLOBAL CONCERN
SEVERE ACUTE RESPIRATORY
SYNDROME (SARS)
Introduction:
Severe Acute Respiratory Syndrome
(SARS) is an acute respiratory illness that has
recently been reported in Asia, North America,
and Europe. The majority of patients identified
as having SARS have been adults aged 25 - 70
years who were previously healthy. Few
suspected cases of SARS have been reported
among children aged <15 years.
Agent suspected to cause SARS:
Scientists at CDC and other laboratories
have detected a previously unrecognized
coronavirus in patients with SARS. Genetic
analysis suggests that this new virus belongs to
the family of coronaviruses but differs from
previously identified coronaviruses .While the
new coronavirus is still the leading hypothesis
for the cause of SARS, other viruses are still
under investigation as potential causes.
Spread of SARS:
The principal way SARS appears to spread
is through droplet transmission; namely, when
someone sick with SARS coughs or sneezes
droplets into the air and someone else breathes
them in. It is possible that SARS can be
transmitted more broadly through the air or from
objects that have become contaminated.
Droplet transmission refers to the spread of
viruses contained in relatively large respiratory
droplets that people project when they cough or
sneeze. Because of their large size, droplets travel
only a short distance (usually 3 feet or less) before
they settle. Droplet transmission can occur either
82
2003; 5(2):170
directly when droplets are inhaled by another
person, or indirectly when droplets land on an
object or surface (such as a doorknob or
telephone) that are then touched by another
individual.
Information to date suggests that people are
most likely to be infectious when they have
symptoms, such as fever or cough. However, it
is not known how long before or after their
symptoms begin that patients with SARS might
be able to transmit the disease to others. Cases
of SARS continue to be reported primarily among
people who have had direct close contact with
an infected person, such as those sharing a
household with a SARS patient and health-care
workers who did not use infection control
procedures while caring for a SARS patient.
Clinical features:
The incubation period for SARS is typically
2-7 days; however, isolated reports have
suggested an incubation period as long as 10 days.
The illness begins generally with a prodrome of
fever (>100.4F [>38.0C]). Fever often is high,
sometimes is associated with chills and rigors,
and might be accompanied by other symptoms,
including headache, malaise, and myalgia. At the
onset of illness, some persons have mild
respiratory symptoms. Typically, rash and
neurologic or gastrointestinal findings are absent;
however, some patients have reported diarrhea
during the febrile prodrome.
After 3-7 days, a lower respiratory phase
begins with the onset of a dry, nonproductive
cough or dyspnea, which might be accompanied
by or progress to hypoxemia. In 10%20% of
cases, the respiratory illness is severe enough to

require intubation and mechanical ventilation.
The case-fatality rate among persons with illness
meeting the current WHO case definition of
SARS is approximately 3%.
The severity of illness might be highly
variable, ranging from mild illness to death.
Although a few close contacts of patients with
SARS have developed a similar illness, the
majority have remained well. Some close contacts
have reported a mild, febrile illness without
respiratory signs or symptoms, suggesting the
illness might not always progress to the
respiratory phase.
Investigations:
Early in the course of disease, the absolute
lymphocyte count is often decreased. Overall
white blood cell counts have generally been
normal or decreased. At the peak of the
respiratory illness, approximately 50% of patients
have leukopenia and thrombocytopenia or low-
normal platelet counts (50,000150,000/L).
Early in the respiratory phase, elevated creatine
phosphokinase levels (as high as 3,000 IU/L) and
hepatic transaminases (two to six times the upper
limits of normal) have been noted. In the majority
of patients, renal function has remained normal.
Initial diagnostic testing should include chest
radiograph, pulse oximetry, blood cultures,
sputum Grams stain and culture, and testing for
viral respiratory pathogens, notably influenza A
and B and respiratory syncytial virus. Clinicians
should save any available clinical specimens
(respiratory, blood, and serum) for additional
testing until a specific diagnosis is made.
Clinicians should evaluate persons meeting the
above description and, if indicated, admit them
to the hospital. Close contacts and healthcare
workers should seek medical care for symptoms
of respiratory illness.
Chest radiographs might be normal during
the febrile prodrome and throughout the course
of illness. However, in a substantial proportion
83
2003; 5(2):171
of patients, the respiratory phase is characterized
by early focal interstitial infiltrates progressing
to more generalized, patchy, interstitial infiltrates.
Some chest radiographs from patients in the late
stages of SARS also have shown areas of
consolidation.
Serum antibody tests, including both
enzyme immunoassay (EIA) and indirect
immunofluorescence antibody (IFA) formats,
have been developed. A positive test result means
that both types of antibody tests were used and
that results for both were positive. At this time,
CDC is interpreting positive test results to
indicate previous infection with this newly
recognized human coronavirus. However, some
people do not test positive until more than 21
days after onset of illness.
Reverse transcription-polymerase chain
reaction (RT-PCR) testing is also available. This
test can detect coronavirus RNA in clinical
specimens, including serum, stool, and nasal
secretions.
Viral isolation for the new coronavirus also
has been done. In these studies, clinical
specimens from SARS patients are co-cultured
with well-characterized cell lines and then
laboratorians look for evidence of coronavirus
replication in these cultured cells.
Several laboratories have reported positive test
results for human metapneumovirus in patients
with SARS. There is not enough information to
determine what role, if any, human
metapneumovirus might have in causing SARS.
Management:
Treatment regimens have included several
antibiotics to presumptively treat known bacterial
agents of atypical pneumonia. In several
locations, therapy also has included antiviral
agents such as oseltamivir or ribavirin. Steroids
have also been administered orally or
intravenously to patients in combination with
ribavirin and other antimicrobials. At present, the
Indian Journal of Practical Pediatrics
most efficacious treatment regimen, if any, is
unknown.
Limiting the spread of SARS:
Infection control precautions should be
continued for SARS patients for 10 days after
respiratory symptoms and fever are gone. SARS
patients should limit interactions outside the
home and should not go to work, school, out-of-
home day care, or other public areas during the
10-day period.
During this 10-day period, all members of
the household with a SARS patient should
carefully follow recommendations for hand
hygiene, such as frequent hand washing or the
use of alcohol-based hand rubs
Each patient with SARS should cover his
or her mouth and nose with a tissue before
sneezing or coughing. If possible, a person
recovering from SARS should wear a surgical
mask during close contact with uninfected
persons. If the patient is unable to wear a surgical
mask, other people in the home should wear one
when in close contact with the patient.
Disposable gloves should be considered for
any contact with body fluids from a SARS
patient. However, immediately after activities
involving contact with body fluids, gloves should
be removed and discarded, and hands should be
washed. Gloves should not be washed or reused,
and are not intended to replace proper hand
hygiene
SARS patients should avoid sharing eating
utensils, towels, and bedding with other members
of the household, although these items can be
used by others after routine cleaning, such as
washing or laundering with soap and hot water.
Common household cleaners are sufficient
for disinfecting toilets, sinks, and other surfaces
touched by patients with SARS, but the cleaners
must be used frequently.Other members of the
household need not restrict their outside activities
unless they develop symptoms of SARS, such as
84
2003; 5(2):172
a fever or respiratory illness.
Suspected Case:
Respiratory illness of unknown etiology
with onset since February 1, 2003, and the
following criteria:
Measured temperature > 100.5F (>38 C)
AND
One or more clinical findings of respiratory
illness (e.g. cough, shortness of breath,
difficulty breathing, hypoxia, or radiographic
findings of either pneumonia or acute
respiratory distress syndrome) AND
Travel within 10 days of onset of symptoms
to an area with documented or suspected
community transmission of SARS (see list
below; excludes areas with secondary cases
limited to healthcare workers or direct
household contacts)
OR
Close contact* within 10 days of onset of
symptoms with either a person with a
respiratory illness who traveled to a SARS
area or a person known to be a suspect SARS
case.
Close contact is defined as having cared for,
having lived with, or having direct contact
with respiratory secretions and/or body
fluids of a patient known to be suspect SARS
case.
Areas with documented or suspected
community transmission of SARS: Peoples
Republic of China (i.e., mainland China and
Hong Kong Special Administrative Region);
Hanoi, Vietnam; and Singapore
Note: Suspect cases with either radiographic
evidence of pneumonia or respiratory
distress syndrome; or evidence of
unexplained respiratory distress syndrome
by autopsy are designated probable cases
by the WHO case definition.
Source : Centre for disease control, Atlanta, USA.

PRACTITIONERS COLUMN
TIPS FOR PRACTISING
PEDIATRICIAN
*Kamlesh R. Lala
**Mrudula K. Lala
Today doctors are practising under the
constant pressure of the society which now a
days see the doctor not as a GOD or messiah, but
simply a professional and has expectations
beyond our abilities to fulfill. Practising doctor
always try to do away with professional hazards
of allegation of unlawful activity and its
sequelae. Following are the tips for the practicing
pediatrisian.
Personality of a doctor
Doctor is expected to be gentle, soft spoken,
well behaved and noble.
Do not smoke or chew pan masala in front
of patient
Dont be overconfident. Never challenge
your colleague. Never criticize.
Do not examine the patient when you are
sick, exhausted or under the influence of
drug or alcohol.
Develop empathy towards patients. Dont
get emotionally attached.
Never talk loose of your colleagues despite
intense professional rivalry.
Never try to challenge anybody.
* Consulting Pediatrician
** Assistant Professor
Department of preventive and social medicine
B. J. Medical College, Ahmedabad
85
2003; 5(2):173
Before the arrival of a patient
Our goal is to cure sometimes, relieve often
but comfort always
Do not prescribe without examining the
patient. Discourage telephonic advice.
Tackle diplomatically.
On arrival of a patient
Receive the patient with a smile.
See the patient as one of your relatives.
Look at him as a Patient only without
taking into consideration caste, religion,
race, politics etc.
Address the patient by his first name which
he likes the most.
Letterhead
Mention your qualifications and designation
on the prescription.
Qualification means recognized degree/
diploma as regulated by Indian Medical
Degree Act 1916, as amended from time to
time.
Mentioning of scholarship, membership and
awards should be avoided.
Mention complete address, your registration
number and telephone numbers along with
timings.
Registration of the patient
Always mention date and time of
consultation. Mention the relation of
informant to patient.
Mention age, sex, weight of the patient.
Enter address and contact number of the
patient
If referred, look at the referring note.
Indian Journal of Practical Pediatrics
History taking
Look carefully. Listen to the patient
attentively. Ask questions intelligently.
Ensure privacy and confidentiality even
during history taking.
Always face the patient. Maintain eye
contact that is comfortable to the patient. Do
not stare.
Check for pregnancy, lactation or any other
pediatric chronic disease.
Take history of drugs being taken. Record
history of drug allergy.
Take family history.
If the patient or relatives are erring on any
account like history not giving a reliable,
refusing investigations, refusing admission,
make a note of it or seek written refusal
preferably in local language.
Examination
Ensure privacy.
Always ensure the presence of a relative or
female attendant before examining a female
patient, even if she is your regular patient.
Never neglect patients complaints.
Expose completely the part to be examined
or you may miss something.
Always put your hand on the part that the
patient says is painful, last.
Do a complete examination including
ausculation.
If after completing the examination, the
patient or attendant feels that something has
been left out or wants something to be
reexamined, oblige him.
Ask the patient to come back for review the
next day, in case you have examined him
hurriedly or if you are not sure.
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2003; 5(2):174
Doctor patient relationship
Try to establish healthy doctor-patient
relationship.
Professional courtesy, confidence and
courage to tell the truth, coordination,
communication, creative and imaginative
thoughts; are all the bridges between doctor
and patient.
Problem arises only when there is lack of a
proper interaction between doctor, patient
and relatives.
Try to understand the feelings of patients and
try to convince them that you are doing /
trying the best.
Do not talk to any angry patient or relative
about any other subject until you understand
the reason for the same. Take necessary time
and steps to calm him down. Be patient with
patients. Patients are always impatient.
Investigations
Investigation is not a substitute for your
clinical judgement. They are only
supportive.
Refer to standard diagnostic centre or to a
qualified doctor.
Routinely advise X - rays in injury to bones
and joints.
Consider the affordability of the patient. Do
only those investigations which are
indicated.
Remember to advise in writing the
investigations required for periodic
evaluation e.g. blood sugar estimation in
diabetes mellitus, CBC in anti cancer drugs,
LFT in hepatotoxic drugs and so on.
Always read reports, interpret the results and
make a note of it.

Conclusion
Never label any condition functional unless
exhaustive examination and investigations
rule out any organic cause.
Do not give high hopes, do not guarantee
cure and be careful while informing the
patient or the relatives about prognosis.
Let the patient know the diagnosis and
treatment of the condition he is suffering
from.
Records
Records should be genuine and not
manipulated.
Records are a must for medico legal, income
tax and consumer protection purposes. A
well kept record is your best friend and best
defence in the court.
Brief, incomplete and cryptic records are of
no use in courts.
Records should not be exhaustive, but should
be brief yet informative and complementary
to management.
Records are based on facts and not on
memory and expected findings. Maintain the
record and not simply keep them.
Medical records for inpatients are to be kept
and maintained for three years from the date
of commencement of treatment.
Keep complete medical record of history,
clinical findings, diagnosis, investigations
and treatment etc.
In complicated cases record precisely the
history of illness and substantiate physical
findings on your prescription.
Mention Diagnosis under review or under
investigation until diagnosis is finally
settled.
Non willingness of the patient for
investigation and admission should be
mentioned in local language.
87
2003; 5(2):175
Consent
Always obtain a legally valid and informed
consent before any surgical or invasive
diagnostic procedure.
Denial of consent should always be
mentioned.
Consent does not give blanket immunity to
a doctor. It is not a protection against
negligence.
Treatment
Do not do anything beyond your level of
competence i.e. qualification, training and
experience.
Always check and recheck injection and
vaccines for name and expiry date. Also
reconfirm the route of administration.
Always use disposables or confirm
sterilization.
Avoid unnecessary injections, IV drugs and
drips. If I will not do it, somebody else
would do it is a wrong way to think.
Justify indication of treatment and
procedures.
In case of any deviation from standard care,
mention reasons.
In an agitated child, restrain him properly
with assistants to avoid needle being broken
inside.
In case a particular drug or equipment is
not available, make a note.
Try to avoid even a minor procedure under
local anesthesia in a consulting room.
Inpatient
An inpatients file should contain
Case papers right from the day of admission
with every personal detail. All examinations
carried out and positive findings.
Indian Journal of Practical Pediatrics
If there are no positive findings, mention No
complaints. GC good.
Investigations carried out and their reports.
Date and time of daily check up and serial
follow up in critical patient.
Record daily vital parameters.
Prescription
General :
Avoid writing ayurvedic formulations.
Do not allow substitute from chemist.
Remember major drug interactions and
special situations like pregnancy and
lactation.
Write names of drugs clearly using capitals,
to avoid confusion with similarly spelled
drugs.
Write in a sequential manner e.g. main drug
first, then supportive and lastly vitamins.
Use correct dose. Do not over prescribe (too
many drugs, larger dose, for longer duration)
or under prescribe.
Mention mode, interval of administration
and instructions in local language.
Specifically mention review and follow up
schedule.
Instructions:
Explain likely side effects of drug and the
actions to be taken if they occur.
In chronic ailments, mention treatment to be
taken immediately in case of emergency e.g.
diazepam in seizures, paracetamol in fever,
antispasmodics in renal colics and so on.
Mention additional precautions e.g. food,
rest, avoidance of certain drugs etc. if
indicated.
Advise accordingly if dose is to be tapered
before stopping.
88
2003; 5(2):176
Remember:
Explain the prognosis and mention it.
Give alternate contact number in case of
emergency and non availability.
Dont forget to provide genetic counselling
to couples and parents with known family
history of children having genetic
abnormalities.
Referring the patient
Create, build and strengthen your
relationship with practitioners of your area
so that they may be of help in crisis.
Prepare a list of specialists and super
specialists whom you trust and have a good
rapport.
Always provide a referring note and if
possible make a phone call. This is liked by
the patient and shows your concern for him.
Keep a record of this reference.
If you are not sure about the diagnosis, do
not hesitate to get the second opinion or to
discuss the case with a friend
Patients have the right for the second
opinion. Let the patient choose another
doctor if he wishes so.
Discharge
Never refuse discharge against medical
advise, as it is his right. Mention it and take
his signature.
Issue a discharge card with every detail of
illness, investigation, treatment, procedures
done etc. for future reference.
Also mention treatment to be taken, follow
up schedule, advice for diet and exercise.
When asked for a written document, never
hesitate to give them. But be careful to enter
all appropriate details before handing over
them.

Death of a patient
Do not leave at the moment of death. Your
presence and experience are most needed.
Remember that the relatives have sustained
a grievous loss.
Keep cool, ignore the comments of others,
and call for assistance if needed.
It would and should appear human if you
forego the fees for the incident that has
triggered off the situation.
Payments
When patient comes, doctor is GOD
When doctor treats him, it is his DUTY.
When bill comes, doctor is a DEMON
So be careful while giving a bill or if possible
tell him rough estimate before starting
treatment or giving costly vaccines.
According to new rules by MCI, a doctor
should display his fees and other charges.
Never be rigid for charges as most of the
troubles start with this only. A craze for
money should not be there.
Do not refuse the patients right to examine
and receive an explanation about your bill.
Certificates
General:
1. Issuing certificate is a tricky job.
2. Use proforma given by MCI. Write your
registration number clearly.
3. Keep duplicate record. Instead of keeping
carbon copy on a plain paper, keep both the
pages same.
4. Always take signature or left thumb
impression on certificate.
5. You can charge reasonable amount for the
certificate.
6. Avoid false certificates diplomatically.
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2003; 5(2):177
Sickness certificate:
1. Never give back dated certificates.
2. Never give it without seeing the patient.
3. Fitness certificate should be issued by a
doctor who has issued illness certificate.
4. Never forecast fitness in advance.
Death certificate:
1. Do not issue it unless you yourself have
verified it and the patient was under your
care for recent illness.
2. State clearly the cause of death and if in
doubt ask for police help.
3. It is to be issued free of charge.
Fees Receipts:
1. Never issue false receipts of fees received.
2. Should be printed, in duplicate and serially
numbered as required by income tax
department.
3. Take the signature of the patient on the
duplicate.
CME
Remember Eyes cannot see what mind does
not know.
Regularly attend CME to update your
knowledge and skill. There is no limit to
knowledge. So even if you feel, you know,
you learn and you will find something new
every time.
Keep with you and refer at times, the latest
edition of the standard textbook of your
branch.
Always attend at least two updates and
conferences every year.
Subscribe at least to one update / journal.
Indian Journal of Practical Pediatrics
Set up
Should have efficient, competent and fast
working manpower.
Update knowledge and skill of your staff
also.
Update facilities and equipments according
to prevailing current standards in your area.
Do not purchase costly sophisticated
equipments only for the sake of prestige. It
may induce you to indulge in malpractice.
Time management
Efforts should be there to have fixed
consulting hours. Those having an overflow
of outpatients, should keep appointment
system.
Discourage home visits as far as possible,
except in emergency.
Give fixed time slot for representatives
during your consultation hours.
Never encourage relatives and visitors
during your busy consulting hours.
Do not forget the importance of your
physical fitness. Allot at least 20-30 minutes
for yourself and your family in your
appointment diary.
Take a weekly off to meet social
commitments and refreshment with your
family.
Take a vacation once or twice a year.
Litigation
When healthy doctor-patient relationship can
be created, evolved, nurtured and
strengthened, no doctor has to fear about any
litigation.
Irritable nature, arrogance and high handed
approach by doctor are his enemies.
90
2003; 5(2):178
Remember that practice of truth is not only
good as a principle but it is good as a policy.
When you have the slightest doubt of
litigation, complete all data meticulously and
preserve them.
Never fail to seek proper legal and medical
advice before filing reply to the notice
received from consumer court.
Never entertain compromise as it may lead
to blackmailing in future and a life time
tension.
Never give away any original to any
authorities. You may give a xerox copy.
This is not an exhaustive account, but is
meant for general information. It is needless to
mention that each situation needs its own
consideration. One will face different situation
every time and so there cannot be the rule of
thumb.
Bibliography
1. Vaidya Jatin P. Doctor in law. Gujarat Med J
1988; 34(1): 21-25.
2. Shah K K and Mehta H P. Doctor and law. pub-
lished by IMA Gujarat State branch, 1994.
3. Jagdish Singh. Dos and donts for Pediatri-
cians, IAP J practical pediatr, 1996; 4(3):
203-207.
4. Jagdish Deshpande. Healthy tips for medical
practice, Knoll pharmaceuticals publication,
2002; pp 1-3.
5. Ajay Agrawal. Time management in General
Practice, Family medicine India (IMACGP).
1996; 1(1):31-32.
6. Family Medicine India (IMACGP), Medical
records for Doctors A must 2001; 5(2): 18-
22.
7. Insight, The consumer magazine, September
2002; 22(5): 1.

QUESTIONS AND ANSWERS
Q.No. 1: Male / 7Yrs. H/O Puffiness and
oedema abdominal wall 7 days. Oliguria. B.P
120/92. No headache/vomiting.Vitals Stable.
Lab: Urine Alb +++ three/four days
consecutive. 8-10 RBC. Granular cast. Blood
Urea-104. S.Creatinine 1.4. S.Cholesterol 360.
C3-Normal. Xray Chest Normal. USG
Abd.Normal.
What are the D/D?
? MCNS (High Cholesterol)
? MPGN Presenting as NS.
? Nephrotic range of protienuria with Acute
Glomerulonephritis. (High Creatinine High
B.P.RBC and granular cast in urine.)
Please guide. Shall we
1. Wait As now S.Creatinine has gone down
to
0.9.(Patient is on Amoxy+Lasix+Nifedipine)
2. Kidney Biopsy?
3. Start Steroid considering NS.
Dr. H.K.Takvani,
Children Hospital and Neonatal Care Centre,
Jamnagar, Gujarat.
A. No.1. This child is presenting with combined
features of nephritic syndrome and nephrotic
syndrome. Serum total protein and serum
albumin values are not available. Lower levels
will support the diagnosis of nephrotic syndrome.
A combination of nephritic and nephrotic
syndrome, hypertension, renal failure and age of
more than 5 years indicate a very high possibility
of non-minimal change disease. Renal biopsy
91
2003; 5(2):179
followed by appropriate management depending
on the histology would be the ideal approach.
Alternatively a course of steroids may be given
if parents are not willing for kidney biopsy even
after adequate explanation about the need of it
for diagnosis and management.
Dr. M.Vijayakumar,
Consultant Pediatric Nephrologist,
Kanchi Kamakoti CHILDS Trust Hospital,
Chennai 600 034.
Q. No.2 i) Rabies can be caused by bite of all
animals except Rat. Is it true?
ii) Rabies rare to be transmitted by Rat.
Harrisons TB of internal medicine.
Dr.Sanjeev Aggarwal
Chandigarh.
A. No.2. In the Red Book 2000 edition of the
American Academy of Pediatrics Committee on
Infectious Diseases under the heading zoonoses
( Diseases transmitted by Animals) page no.776,
Appendix vii Common animal sources for Rabies
transmission are stated as Dogs, Cats, Ferrets,
Bats, Skunks, Foxes & Wood Chucks and the
mode of transmission is by bites. Hence Rat
Bites do not transmit rabies.
Dr.A.Parthasarathy,
Retd. Senior Clinical Professor of Pediatrics,
Madras Medical College,
Deputy Superintendent, Institute of Child
Health & Hospital for Children.Chennai.
Indian Journal of Practical Pediatrics
Q. No.3. Indrawing in respiratory distress. In
case of respiratory distress, suprasternal,
intercostal and subcostal indrawing is seen. Is
it a real indrawing or a visual deception? My
perception is that because of the underlying
pathology, lung expansion is restricted, while
the thoracic cage moves out normally causing
the illusion that some portion of the thoracic
cage is moving inwards. Why does the
indrawing occur?
Dr.Yash Paul,
Consultant Pediatrician, Jaipur 302 016.
A. No.3. Normal breathing is effortless.
Breathlessness, dyspnoea, respiratory distress, all
means increased work of breathing, characterized
by sub-costal retractions, intercostal retractions,
suprasternal hollowing and flaring of alae nasi.
Flaring of alae nasi is a sign of increased airway
resistance with breathing through the nose. 50%
of the resistance of airflow occurs in the nose
whereas the other 50% occurs in the large
airways. With obstruction in the airways the
infant can decrease total airway resistance by
flaring the alae nasi and thus decreasing the
resistance in the nose. Retractions is a sign of
increased work of breathing. Normally tidal
volume breathing generates a negative
intrathoracic pressure of 4-5 cms of water.
Retractions occur when the negative intrathoracic
pressure is increased as in individuals with airway
CONTRIBUTORS TO CORPUS FUND OF IJPP
Rs. 1000/-
Dr. V.P.Anitha, Chennai, Tamilnadu
Dr. L.S. Kadam, Pune, Maharashtra
Dr. Suresh K. Kakhandaki, Bagalkot, Karnataka
Dr. K.K. Agarwal, Rajasthan
Dr. H.V. Kotturesha, Shimoga, Karnataka
Dr. K.H. Vimala, Bangalore, Karnataka
92
2003; 5(2):180
obstruction or poorly complaint lungs.
Suprasternal hollowing are especially striking in
extrathoracic airway obstruction, in which the
large negative intrathoracic pressure that
attempts to overcome the obstruction, results in
collapse of extrathoracic airways. Intracostal
retraction is a sign of increased lung stiffness or
increased work of breathing due to airway
obstruction. Subcostal retractions are always a
sign of hyperinflation and a flattened diaphragm
due to small airway obstruction. Normally when
the dome shaped diaphragm contracts and moves
into the abdomen, the lower edge of the ribcage
to which the anterior edge of the diaphragm is
attached, moves upward and outward. In the
presence of hyperinflation, the diaphragm is
depressed and when it contracts and moves
further into the abdomen, it pulls the lower edge
of the ribcage inwards resulting in subcostal
retractions. Clinically, the presence of subcostal
retraction means hyperinflation, when retraction
is worsening, small airway obstruction is
worsening; when retraction is decreasing in
severity, the degree of air trapping is lessening.
So indrawing in respiratory distress is a real
indrawing and not a visual deception.
Dr.L.Subramanyam,
Consultant in Pediatric Pulmonology,
Kanchi Kamakoti CHILDS Trust Hospital,
Chennai 600 034.
Rs. 500/-
Dr. B.I. Sasireka, Chennai, Tamilnadu
Dr. Mahesh Patel, Surat, Gujarat
Dr. S. Bose, Durgapur, West Bengal
Dr. K.M. Manoharan, Chennai, Tamilnadu
 2003; 5(2):181

NEWS AND NOTES

The Rheumatology Chapter of IAP & Mumbai Branch Of IAP invite you to the
The 1st National Conference in Pediatric Rheumatology
ARTICULATIONS IN PEDIATRIC RHEUMATOLOGY
Venue: R D Choksi Auditorium,Golden Jubilee Building,Tata Memorial
Hospital,Parel,Mumbai 400013
Dates: Sat. 8th November-10am-6pm and Sun. 9th November-9am-4pm
Registrations-(last date 30.9.03limited to 200 only)No spot registrations
(includes delegate kit, course material, lunches and coffee breaks)
before 31.07.03 after 31.07.03
IAP Rheumatology Chapter Members Rs 800 Rs 1200
Others * Rs 1000 Rs 1500
Post graduates/Residents(40 only) Rs 600 Rs 900
(letter from HOD required)
Cheques/DD to be drawn favouring IAP Rheumatology Chapter payable in Mumbai (outstation
cheques add Rs. 50)
*enroll as Rheumatology Chapter Life Member(Life membership Rs500) and avail of cheaper
registration. Send separate cheque/DD. Refund last date 30.09 .03 -50% after conference. All payments
and correspondence to:
Dr Raju Khubchandani, 31 Kailas Darshan, Kennedy Bridge Mumbai 400007,
Tele O- (022) 23865522, R-(022)22028388, Fax(022) 23898362, Email rajukay@hotmail.com
cut here or attach a letter stating below facts
THE 1ST NATIONAL CONFERENCE IN PEDIATRIC RHEUMATOLOGY
ARTICULATIONS IN PAEDIATRIC RHEUMATOLOGY
PERSONAL DETAILS
Name:
Institution Designation
Consultant\Student Paediatrics\Other (specify)
Address (include pin code)
Phone: Res( ) Mobile Fax:( ) Email
Food preference Veg\Non-veg
Need assistance with staying arrangements? Yes/No -We will mail you options
(e mail id essential)
Remittance Cheque/DD no Bank Branch
Signature

93
Indian Journal of Practical Pediatrics 2003; 5(2):182

NEWS AND NOTES

SOUTH PEDICON 2003

XVII SOUTH ZONE CONFERENCE OF IAP
&
XXVIII ANNUAL CONFERENCE OF IAP - TNSC
Organized by
IAP North Arcot Branch &
Christian Medical College & Hospital, Vellore, Tamilnadu
Date : September 4,5 & 6, 2003.
Venue : Christian Medical College & Hospital, Vellore, Tamilnadu
Registration Fees
Category of Before Before Before From 1.8.2003 &
delegates 15.4.2003 31.5.2003 31.7.2003 Spot
IAP Member Rs.1000/- Rs. 1500/- Rs. 2000/- Rs.3000/-
Non IAP Member Rs. 1500/- Rs. 2000/- Rs. 2500/- Rs. 3250/-
PG student Rs. 900/- Rs. 1150/- Rs. 1400/- Rs. 1750/-
Accompanying person Rs. 1000/- Rs. 1500/- Rs.2000/- Rs. 3000/-
Foreign Delegates US$ 200 US$300 US$400 US$500

For preconference concurrent workshops (on 3rd September 2003) Rs.500/- each*
1. Intensive Care 2. Clinical Epidemiology 3. NALS
* Can register for only one workshop

For further details contact:

Dr. Chellam Kirubakaran,
Organising Secretary, South Pedicon 2003, Department of Pediatrics,
Christian Medical College & Hospital, Vellore, Tamilnadu 632 004.
Phone No. (0416) 2262603, 2221346

94
 2003; 5(2):183

PEDICON 2004
41st NATIONAL CONFERENCE OF THE INDIAN ACADEMY OF PEDIATRICS
Healthy child - Mighty IIndia
ndia
8-11 January 2004, Chennai
Venue: Sri Ramachandra Medical College & Deemed University,
Porur, Chennai, Tamilnadu 600 116

The metropolitan city of Chennai known for its excellent hospitality and good ambience, invites
you to the 41st National Conference of the Indian Academy of Pediatrics at Sri Ramachandra
Medical College and Deemed University, Porur, Chennai between 8-11 January 2004. The theme
of the conference is Healthy child - Mighty India. The pediatricians of the city of Chennai
eagerly await to host this prestigious event after a span of 17 years by providing academic feast to
fellow pediatricians from India and abroad.
Dr. C.S. Rex Sargunam Dr. A. Balachandran Dr. M.P. Jeyapaul
Organising Chairman Organising Secretary Hon. Treasurer

Category Before Before Before Before From 1.12.2003

30.4.2003 30.08.2003 30.10.2003 30.11.2003 & Spot
IAP Member Rs.2300 Rs.2800 Rs.3500 Rs.4500 Rs.5500
Non IAP member Rs.2500 Rs.3000 Rs.3800 Rs.4800 Rs.6000
Accomp. person Rs.2000 Rs.2500 Rs.3000 Rs.4000 Rs.4500
PG Student # Rs.2000 Rs.2500 Rs.3000 Rs.4000 Rs.4500
Senior citizen ## Rs.2000 Rs.2500 Rs.3000 Rs.4000 Rs.4500
SAARC delegate Rs.2500 Rs.3000 Rs.3800 Rs.4800 Rs.6000
Foreign delegate US $ 200 US $ 250 US $ 350 US $ 400 US $ 500
Cancel/Refund * 70% 60% 50% 30% Nil

# PG student should submit the bonafide certificate

## Senior citizen > 65 years
* Refund will be done one month after the conference
** Details regarding the preconference workshops (on 7.1.2004) will be intimated later
For further details contact:
Dr. A. Balachandran,
Organising Secretary, PEDICON 2004,
IAP - TNSC Flat, Ground Floor, F Blook, Halls Towers,
56 (Old No.33) Halls Raod, Egmore, Chennai 600 008.
Phone: 044-28190032, 28191524 Email: pedicon2004@yahoo.com
95
Indian Journal of Practical Pediatrics 2003; 5(2):184

REGISTRATIONFORM
PEDICON2004
41st NATIONAL CONFERENCE OF INDIAN ACADEMY OF PEDIATRICS
Healthy child - Mighty IIndia
ndia
Venue: Sri Ramachandra Medical College & Deemed University, Porur, Chennai 600 116
Delegates Title [ ] Dr. [ ] Prof. [ ] Mr. [ ] Mrs. [ ] Ms. IAP Membership No...............................
Name ......................................................................................................................................................
Mailing address .....................................................................................................................................
Building/ Institution Name ....................................................................................................................
Flat/Room No. .......................................................................................................................................
Street Name ...........................................................................................................................................
Locality / Suburb ...................................................................................................................................
City / District .........................................................................................................................................
State .................................................................... Pin-code ...............................................................
Residence STD Code ......................................... Phone no. ..............................................................
Clinic/Hospital STD Code ................................. Phone no. ..............................................................
Fax No. ............................. Mobile No. ................................. Pager No. ..............................................
E-mail ....................................................................................................................................................
Food Preference [ ] Vegetarian [ ] Non vegetarian CME : Yes / No
IAP Delegate Fees Rs. .....................................................
Non-IAP Delegate Fees Rs. .....................................................
PG Student Fees Rs. .....................................................
Accompanying person Rs. .....................................................
Others Rs. .....................................................
Demand Draft Number............................................. of .......................................... Bank
.......................................... Branch dated ...............................
Please Note: Signature
* CME is free, however, prior registration is a must.
* Please send your payment only by demand draft. Please do not send any cash by post. Please do
not use cheque for payment. Demand draft to be made in favour of Pedicon 2004, payable at
Chennai.
* Please mail the registration form along with the Demand Draft by registered post or by courier only
to the following address.
Secretariat:
Dr. A.Balachandran, Organizing Secretary, PEDICON 2004,
IAP-TNSC Flat, Ground Floor, F Block, Halls Towers, 56 (Old No.33) Halls Road, Egmore,
Chennai-600 008. Tamilnadu, India.
Phone: 28190032, 28191524, Email: pedicon2004@yahoo.com

96
 2003; 5(2):185

INDIAN JOURNAL OF PRACTICAL PEDIATRICS

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committed to practical pediatric problems and management update

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Indian Journal of Practical Pediatrics
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56 (Old No.33), Halls Road,
Egmore, Chennai - 600 008. India
Phone : 2819 0032
Email : ijpp_uap@rediffmail.com

9796
Indian Journal of Practical Pediatrics 2003; 5(2):186

98
 2003; 5(2):187

Indian Journal of
Practical Pediatrics
Subscription Journal of the
IJPP
Indian Academy of Pediatrics

JOURNAL COMMITTEE
NATIONAL ADVISORY BOARD
Editor-in-Chief
Dr. A.Balachandran President, IAP
Executive Editor
Dr. H.P.S.Sachdev
Dr. D.Vijayasekaran
Managing Editor
Dr. K.Nedunchelian President Elect, IAP
Associate Editors
Dr.M.K.C.Nair
Dr. N.C.Gowrishankar
Dr. Malathi Sathiyasekaran
Dr. P.Ramachandran
Editor, Indian Pediatrics
Dr. C.V.Ravisekar
Dr. Panna Choudhury
Dr. S.Thangavelu
Executive Members
Dr. B.Anbumani Members
Dr. Janani Shankar
Dr. Ashok K.Rai
Dr. P.S.Muralidharan
Dr. K.Nagaraju Dr. C.M.Chhajer
Dr. T.L.Ratnakumari Dr. S.R.Keshava Murthy
Dr. T. Ravikumar
Dr. Krishan Chugh
Dr. S.Shanthi
Dr. So.Shivbalan Dr. B.R.Nammalwar
Dr. V.Sripathi Dr. A.Parthasarathy
Dr. Nitin K.Shah
Dr. M.Vijayakumar
(Ex-officio)
Dr. Vijay N.Yewale
Indian Journal of Practical Pediatrics
IAP Team - 2003
President
Dr. H.P.S. Sachdev
Dr. Apurba Kumar Ghosh (West Bengal)
President Elect
Dr. M.K.C.Nair
Imm. Past President Dr. M.Dasaradha Rami Reddy (Andhra Pradesh)
Dr. Dilip K.Mukherjee
Vice President
Dr. C.P.Bansal
Secretary General
Dr. Nitin K. Shah
Treasurer
Dr. Bharat R. Agarwal
Editor-in-Chief, IP
Dr. Panna Choudhury
Editor-in-Chief, IJPP
Dr. A. Balachandran
Joint Secretary
Dr. D.Vijayasekaran
2003; 5(2):188
Indian Academy
of Pediatrics
Kailash Darshan,
Kennedy Bridge,
Mumbai - 400 007.
Members of the Executive Board
Dr. C.M.Aboobacker (Kerala)
Dr. Ashok Kumar Gupta ( )
Dr. Ashok K.Rai ( )
Dr. Baldev S.Prajapati (Gujarat)
Dr C.P.Bansal (Madhya Pradesh)
Dr. C.M. Chhajer (Tripura)
Dr. K.W.Deoras (Chhattisgarh)
Dr. D.Gunasingh (Tamil Nadu)
Dr. S.R.Keshava Murthy (Karnataka)
Dr. Krishan Chugh (Delhi)
Dr. Mahesh Kumar Goel ( )
Dr. Manoranjan Sahay (Jharkhand)
Dr. Niranjan Mohanty (Orissa)
Dr. P.S.Patil (Maharashtra)
Dr. K.R.Ravindran (Tamil Nadu)
Dr. Ramesh K.Yelsangikar (Karnataka)
Dr. Sailesh G.Gupta (Maharashtra)
Dr. Satish V.Pandya (Gujarat)
Dr. (Mrs). Shabina Ahmed (Assam)
Dr.Shahshi B.P.Singh (Bihar)
Dr. S.C.Singhal (Haryana)
Dr. B.K.Sudhindra (Kerala)
Dr. Sudesh K.Sharma (Punjab)
Dr. Suil Gomber (Delhi)
Dr. Tapan Kumar Ghosh (West Bengal)
Dr. Vijay N.Yewale (Maharashtra)
Dr. R.Virudhagiri (Tamil Nadu)
Dr. Yashwant Patil (Maharashtra)
 2003; 5(2):189

CONTRIBUTORS TO CORPUS FUND OF IJPP

Rs. 1000/- Rs. 500/-

Dr. V.P.Anitha, Chennai, Tamilnadu
Dr. B.I. Sasireka, Chennai, Tamilnadu
Dr. L.S. Kadam, Pune, Maharashtra
Dr. Suresh K. Kakhandaki, Bagalkot, Karnataka Dr. Mahesh Patel, Surat, Gujarat
Dr. K.K. Agarwal, Rajasthan Dr. S. Bose, Durgapur, West Bengal
Dr. H.V. Kotturesha, Shimoga, Karnataka
Dr. K.M. Manoharan, Chennai, Tamilnadu
Dr. K.H. Vimala, Bangalore, Karnataka
 2003;5(4)271

INDIAN JOURNAL OF IJPP

PRACTICAL PEDIATRICS
A quarterly medical journal committed to practical pediatric problems and
management update presented in a readable manner
IJPP is a subscription Journal of the Indian Academy of Pediatrics
Indexed in Excerpta Medica from January 2003
Annual subscription:Rs. 300/- 10 years subscription:Rs.3000/-
Vol.5 No.4 OCT-DEC 2003
Dr. A. Balachandran Dr. D.Vijayasekaran
Editor-in-Chief Executive Editor

CONTENTS
FROM THE EDITOR'S DESK 273

TOPIC OF INTEREST - HIV INFECTION

Editorial : Indian perspective of HIV infection in children 275
- Nitin K Shah
Epidemiology of HIV in India 277
- Joshi PL, Tripti Pensi, Rewari BB
IV drug abuse and HIV in North-Eastern India 283
- Brajachand Singh Ng, Chourjit Singh Ksh
Clinical manifestations of HIV infection in children 286
- Rakesh Lodha, Kabra SK
Laboratory diagnosis of pediatric HIV 298
- Shivananda, Rajath A
General management of HIV in children 303
- Mathur YC, Rajiv Chandra Mathur
Journal Office: Indian Journal of Practical Pediatrics, IAP-TNSC Flat, F Block, Ground Floor, Halls Towers,
56, Halls Road, Egmore, Chennai - 600 008. INDIA. Tel.No. : 044-28190032 E.mail : ijpp_iap@rediff mail.com
Address for registered/insured/speed post/courier letters/parcels and communication by various authors:
Dr. A. Balachandran, Editor-in-chief, Indian Journal of Practical Pediatrics, F Block, No. 177, Plot No. 235,
4th Street, Anna Nagar East, Chennai - 600 102. Tamil Nadu, INDIA.

1
Indian Journal of Practical Pediatrics 2003;5(4)272

Counselling in pediatric HIV / AIDS 306

- Swati Y Bhave
Opportunistic infections in pediatric HIV disease 314
- Rinku Agarwal, Milind S Tullu, Sandeep B Bavdekar
Antiretroviral therapy 325
- Archana Kher
Prevention of mother to child transmission of HIV 337
- Nitin K Shah, Khyati Mehta, Mamta Manglani
RADIOLOGIST TALKS TO YOU
Abdominal mass 348
- Vijayalakshmi G, Natarajan B, Ramalingam A
PRACTITIONERS COLUMN
Hearing loss in children: Need for early detection and intervention 353
- Abraham K Paul
CASE STUDY
Images in pediatrics: Cleidocranial dysostosis 356
- Sujatha L, Lakshminarayanan S, Srivenkateswaran K, Venkatesh AL
Vaginal voiding as a cause of recurrent urinary tract infection 358
- Sripathi V, Vijayakumar M
Podophyllin poisoning - a case report 360
- Ravisekar CV, Kumarasamy K, Sathyamurthy B, Venkataraman P,
Harish V Sutrave, Vasanthamallika TK
QUESTIONS AND ANSWERS 362
BOOK REVIEW 276, 359
AUTHOR INDEX 363
SUBJECT INDEX 364
NEWS AND NOTES 313,336,347,352,355,357,361,362
FOR YOUR KIND ATTENTION
* The views expressed by the authors do not necessarily reflect those of the sponsor or
publisher. Although every care has been taken to ensure technical accuracy, no responsibility is
accepted for errors or omissions.
* The claims of the manufacturers and efficacy of the products advertised in the journal are
the responsibility of the advertiser. The journal does not own any responsibility for the guarantee
of the products advertised.
* Part or whole of the material published in this issue may be reproduced with
the note "Acknowledgement" to "Indian Journal of Practical Pediatrics" without prior permission.
- Editorial Board
2

FROM THE EDITORS DESK
We have been publishing this journal since
January 1993 and will be completing eleven years
in December 2003. The journal has been indexed
in Excerpta Medica and journal committee is
striving to maintain the high standards.
We are thankful to all our reviewers for peer
reviewing the articles, various experts in their
respective fields for answering the queries raised
by our readers and for the valuable suggessions
and guidance offered by our senior faculty and
colleagues.
This issue will highlight on HIV infection
in children. Our guest editor for this issue is
Dr. Nitin K. Shah, Programme Co-ordinator, IAP
Project on Child to Adolescent HIV/AIDS and
Honorary Pediatrician, LTMG Hospital,
Mumbai. With his vast experience and
knowledge he has carefully chosen the topics and
authors suitably for both academicians and
practitioners point of view. In his editorial, he
has given a brief outline on the current scenario
on HIV infection in children.
Epidemiology of HIV in India written by
Dr.Joshi et al is thought provoking and has
projected the major challenge for India in the
future on preventive programmes. Dr Chourjit et
al has written about IV drug abuse and HIV in
North Eastern India.
Published and owned by Dr. A. Balachandran, from Halls Towers, 56, Halls Road,
Egmore, Chennai - 600 008 and printed by Mr. D. Ramanathan, at Alamu Printing Works,
9, Iyyah Mudali Street, Royapettah, Chennai - 600 014. Editor : Dr. A. Balachandran.
3
2003;5(4)273
Clinicial manifestations of HIV infections
in children is enumerated very well by Dr. Kabra
et al. In his article on laboratory diagnosis of
pediatric HIV, Dr.Shivanandha has outlined the
various laboratory tests available to detect HIV
infection. Dr.Mathur et al have given us an
overview of the basic treatment principles of
pediatric HIV infection.
As vividly narrated by Dr.Swati Y Bhave,
in the fight against HIV/AIDS more than the
drugs and other interventions, counselling is
indispensible. Dr.Rinku Agarwal et al has
highlighted that efforts should be made to identify
the causative organisms so that early treatment
can be instituted against opportunistic infections.
The review on antiretroviral therapy by
Dr.Archana Kher will provide the primary care
physician with practical information on drugs that
are available for treatment. Dr. Nitin K. Shah et-
al have discussed the various protocols available
to prevent the mother to child transmission.
We are grateful to Dr.Nitin K.Shah for his
wonderful work as Guest Editor for this important
issue on HIV infection. His work for this issue
as a Guest Editor and his untiring involvement
in bringing out this issue will be remembered by
every one in IJPP. We thank all the authors for
their contribution in this issue
Indian Journal of Practical Pediatrics
CHECK LIST
CHECKLIST FOR INDIAN JOURNAL
OF PRACTICAL PEDIATRICS
The checklist must accompany the
manuscript.
General
Original articles which have not been
published elsewhere are invited and should
be sent to the Editor. They are considered
for publication on the understanding that
they are contributed to this journal solely.
Four complete sets of the manuscript are
submitted.
Manuscript is typed double-space
throughout with wide margin on one side of
paper only including the list of references
and tables.
Manuscript is arranged as follows: Title
page, text, acknowledgements, references,
tables, figure legends, figures.
All pages are numbered at the top of the right
corner, beginning with the title page.
The letter of submission has been signed by
all authors.
Submission of Floppy Disc
Two copies of the articles plus a floppy disc
of the wordprocessed manuscript and a list of
any nonstandard characters that were used in the
disc should be submitted in the usual manner.
The preferred storage medium is a 3.5 inch disc
in MS-Word compatible format. The publisher
is under no obligation to use the submitted floppy
disc, but will make every attempt to do so.
Text
Only generic names should be used
Measurements must be in metric units with
System international (SI) Equivalents given
in parentheses.
4
2003;5(4)274
Title page
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Identified in the text by Arabic numerals in
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Type double-space on separate sheets and
numbered consecutively as they appear in the
text.
Abbreviations of journals conform to the
style of Indian Journal of Practical Pediatrics.
Typed as illustrated in Instructions to
authors with correct punctuation.
Checked carefully by the author(s).
Tables
Numbered with Roman numerals and typed
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explanatory notes below the table.
Figures and legends
Not larger than 15cm x 20 cm.
Unmounted and with figure number, first
authors name and top location indicated on the
back of each figure. Legends typed double-space
on separate sheet. No title on figure.
Each manuscript must be accompanied by
a letter of declaration to be signed by each author
to confirm that he has seen, read and approved
it.
All manuscripts which are rejected will not
be returned to author. Those submitting articles
should therefore ensure that they retain at least
one copy and the reference numbers, if any, of
the illustration.
Authors Signatures.

EDITORIAL
INDIAN PERSPECTIVE OF HIV
INFECTION IN CHILDREN
As on today, approximately 40 million
people live with HIV infection world over. This
includes approximately 4-5 million children with
HIV infection. More than 90% of these patients
are living in developing countries that neither
have adequate resources nor the required
infrastructure to tackle this problem. With the
result, HIV infection continues to spread
unabated in these countries. Some of the sub -
Saharan African countries have 25%
seroprevalence of HIV infection in the general
population. Such countries are already
experiencing doubling of the infant mortality
rates, pushing these countries down in their health
statistics by more than 2 to 3 decades.
Today India has approximately 4 million
people living with HIV infection. Six states
namely Maharashtra, Tamil Nadu, Andhra
Pradesh, Karnataka, Manipur and Nagaland are
high prevalence states. They have more than 1%
seroprevalence of HIV infection amongst
pregnant women attending the antenatal clinics.
These states are doing relatively well in their
childhood health statistics at present. However
HIV related mortality could upset all the gains
achieved in the last couple of decades with efforts
like breast-feeding promotion, ARI and diarrhoea
control program, immunizations etc. Rest of the
country has low or intermediate HIV prevalence.
However some of these states are still lagging
behind in their health statistics, and spread of HIV
infection is likely to make the scene worse in
these states.
Pediatric HIV infection occurs mainly
through vertical route. Twenty eight million
5
2003;5(4)275
deliveries occur in India annually. The average
HIV prevalence in these pregnant women is
0.5%. This means 1.4 lakh deliveries occur in
HIV infected women. Without any intervention,
30% of these HIV infected women will transmit
HIV infection to their babies. It means that
approximately 40,000 babies are HIV infected
vertically in India annually. This figure could be
higher than this if the seroprevalence is actually
more than estimated. With effective measures of
prevention of mother to child transmission 50-
60% of these babies could be prevented from
getting HIV infection, which means 20000-40000
babies can be salvaged by effective prevention
of mother to child transmission (PMTCT)
program. PMTCT program is a formidable yet
rewarding exercise. The phase I and II Indian
feasibility studies of prevention of mother to child
transmission have shown good results and the
benefits should now percolate down to the
masses.
Less than 10% of the HIV infected patients
can afford the ideal treatment in India. It is futile
to treat these patients with haphazard anti -
retroviral drugs without proper counselling. The
need of the hour is to prevent HIV infection
through mass education, counsel those who are
already infected about the importance of treating
their opportunistic infections, complete childhood
immunization as per the guidelines for the
children, treat the associated sexually transmitted
infections (STI), offer voluntary counselling and
testing of pregnant women attending the antenatal
clinics and offer the prevention of mother to child
transmission measures to those who are found
HIV infected. It is important that we train the
physicians in these aspects of HIV infection so
Indian Journal of Practical Pediatrics 2003;5(4)276

that they could diagnose HIV infection early and
guide the patients to the best possible treatment
within the constraints. Indian Academy of
Pediatrics has taken up the responsibility of
spreading these messages to our members
through the IAP HIV/AIDS project. In the last 3
years we have conducted more than 14 state level
workshops and hope to continue it in the future.
We have evolved the training manual for our
members, which will help our members to offer
correct treatment of HIV infection in children.
This special issue of IJPP has articles, which
will discuss the various aspects of HIV infection
in children written by experts in childhood HIV
infection. I am sure that this special issue will
serve the purpose as a ready reckoner for the
readers.
Nitin K. Shah
Programme Co-ordinator,
IAP Project on Child to Adolescent HIV/AIDS
Honorary Pediatrician, U.H.C,
LTMG Hospital, Mumbai.

BOOK REVIEW

Title : Blood Gas Analysis A Practical Approach

Author : Dr.T.Shyam Sunder
Review : This is the first book written by an Indian author on Blood Gas Analysis. This
is commendable work. The author is an anesthetist. The most appreciable aspect of this book is its
simplicity. Even complicated aspects are discussed in a simple manner. In the initial five chapters,
the author has taken sincere efforts to explain the basic principles including the terminology. The
chapter on collection of sample is written stepwise. However inclusion of diagrams would have
made it self-explanatory. All the four acid base disturbances (Metabolic acidosis and alkalosis,
respiratory acidosis and alkalosis) are analyzed in depth. Author has used algorithms to identify the
underlying cause. The best part of the book are the last four chapters. A seven-step approach has
been given to solve the mystery of acid base disturbances followed by case scenarios, self-assessments
and FAQs. The book is very handy as a pocket book for reference with a colourful cover, nice
printing with highlights and is also economically priced. As all the case scenarios and underlying
causes are adult oriented, inclusion of a few pediatric cases and common causes observed in children
would have made the book complete. From his experience, he could have written about the choice
of ABG machines and about its maintenance. This could have been more useful for pediatricians
who handle ABG machines in their institutions. There is some minor lacunae in the last minute
works in the press title is incomplete in the cover without the word practical approach, title of
chapter five is missing and there are a few spelling mistakes. However these do not undermine the
fantastic work of the author. This book is strongly recommended for Pediatric Students,
Neonatologists, Pediatricians working in intensive care units and also for critical care nurses.
Publisher : M/s Paras Medical Publisher,
5-1-473, Putilibowli, Jambagh Road,
P.O.Box Number 544,
Hyderabad 500 095. A.P. India

Price : Rs.125/-

6

HIV INFECTION
EPIDEMIOLOGY OF HIV IN INDIA
WITH SPECIAL REFERENCE TO
CHILDREN
* Joshi PL
** Tripti Pensi
*** Rewari BB
Abstract: The AIDS epidemic has claimed more
than 3 million lives in 2002, and an estimated 5
million new people acquired the human immuno-
deficiency virus (HIV) the same year bringing
the number of people living with the virus
globally, to 42 million.
The window opportunity of bringing the
HIV/AIDS epidemic under control is narrowing
rapidly in Asia. There is a vital need to expand
activities that focus on people most at risk of
infection. But targeted interventions alone will
not halt the epidemic. More extensive HIV/AIDS
programmes that reach the general population
are essential.
Keywords : Epidemiology, HIV, India, Children.
One of the salient achievements of the
twentieth century science is the triumph of
medical fraternity over various infectious
diseases, which have plagued mankind through
* Additional Director
National AIDS Control Organisation
Chandralok Building
Janpath, New Delhi
** Head of the Unit
Department of Pediatrics
Dr. R.M.L Hospital, New Delhi
*** Medical Specialist
Dr. R.M.L. Hospital, New Delhi
7
2003;5(4)277
the ages. Many deadly diseases like small pox
and guinea worm have been eradicated, diseases
like leprosy and polio are on the verge of
elimination and many others are fairly controlled.
Modern medicine has assured a reasonably good
quality of life to mankind. But this happy scenario
was rudely shattered in the early eighties when a
new virus, later identified as Human
Immunodeficiency Virus (HIV), struck the
human race with consequences. Till date, all the
ingenuity of man, money, effort and power has
not found a way to counter the relentless
onslaught of HIV which respects no territorial
boundaries, makes no distinction between race,
creed or colour and spares neither the rich nor
the poor, neither the old nor the young.
The problem
As the world enters the third decade of the
AIDS epidemic, the evidence of its impact is
undeniable. Wherever the epidemic has spread
unchecked, it is robbing countries of the resources
and capacities on which human security and
development depend. In some regions, HIV/
AIDS, in combination with other crises, is driving
ever-larger parts of nations towards destitution.
In Eastern Europe and Central Asia, the
number of people living with HIV in 2002 stood
at 1.2 million. HIV/AIDS is expanding rapidly
in the Baltic States, the Russian Federation and
several Central Asian republics.
In Asia and the Pacific, 7.2 million people
are now living with HIV. Almost 1 million people
acquired HIV in 2002, a 10% increase since 2001.
A further 490, 000 people are estimated to have
died of AIDS in the past year. About 2.1 million
young people (aged 1524) are living with HIV.
Indian Journal of Practical Pediatrics
The growth of the epidemic in this region is
largely due to the growing epidemic in China,
where a million people are now living with HIV
and where official estimates foresee a manifold
increase in that number over the coming decade.
There remains considerable potential for growth
in India, too, where almost 4 million people are
living with HIV.
In several countries experiencing the early
stages of the epidemic, significant economic and
social changes are giving rise to conditions and
trends that favour the rapid spread of HIVfor
example, wide social disparities, limited access
to basic services and increased migration.
Both China and India, are experiencing
serious, localized epidemics that are affecting
many millions of people.
Indias national adult HIV prevalence rate
of less than 1% offers little indication of the
serious situation facing the country. An estimated
3.97 million people were living with HIV at the
end of 2002the second-highest figure in the
world, after South Africa. HIV prevalence among
women attending antenatal clinics was higher
than 1% in Andhra Pradesh, Karnataka,
Maharashtra, Manipur, Nagaland and Tamil
Nadu.
Recent trends in India
Since the detection of HIV infection in
commercial sex workers (CSWs) in Tamil Nadu
in 1986, there has been a steady increase in the
number of AIDS cases seeking treatment in
various hospitals across the country. A
cumulative total of 20,304 cases of AIDS had
been reported to the National AIDS Control
Organisation (NACO) till 31st March 2001. With
an estimated number of 3.86 million HIV
infections in the country, the number of AIDS
cases is likely to continue to increase in the
coming years.
8
2003;5(4)278
The total number of estimated HIV
infections among adult population based on
nationwide sentinel surveillance data collected
in the year 1998, 1999 and 2000 reveals that there
is no dramatic upsurge in the spread of HIV
infection in the country. It was 3.5 million
infections in the year 1998, 3.71 million in the
year 1999 and 3.86 million in the year 2000.
Based on HIV prevalence rates in adult
population in States/Union Territories, estimated
from National Sentinel Surveillance round
conducted during the period August to October
2000,(Fig.1) States/Union Territories have been
classified into three groups as follows:
Group-I The states like Maharashtra,
(High Tamil Nadu, Karnataka, Andhra
prevalence Pradesh, Manipur and Nagaland
states) where the HIV infection has
crossed 1% or more in antenatal
women.
Group-II The states like Gujarat, Goa and
(Moderate Pondicherry where the HIV
prevalence infection has reached 5% or
states) more among high risk groups but
the infection is below 1% in
antenatal women.
Group-III The remaining states where the
(Low HIV infection in any of the high
prevalence risk groups is still less than
states) 5% and less than 1% among
antenatal women. (Fig.1)
As on date 37,566 AIDS cases were reported
to NACO. These figures are considered only a
fraction of AIDS morbidity. The low numbers
and geographic distribution of AIDS cases shows
that these numbers do not reflect the true situation
in the country and there may be gross under
reporting. (Fig.2)
 2003;5(4)279

Epidemiological analysis of reported AIDS
cases reveals that:
1. The disease is affecting mainly the people
in the sexually active age group. The
majority of the patients are in the age group
of 15 - 44 years
2. Males account for 78.5% of AIDS cases and
females 21.5%. the ratio being 3:1, but now
more and more women are being infected.
3. The predominant mode of transmission of
infection in the AIDS patients is through
heterosexual contact (84.5%), followed by
blood and blood product infusion (3.27%),
injectable drug use (3.36%), perinatal route
(2.14%) and others 6.7% (Fig 3).
4. The major opportunistic infection in the
AIDS patients in our country is tuberculosis
(65%) indicating a threat of dual epidemic
of TB and HIV in the future.
5. The major presenting signs and symptoms
in AIDS cases in India are weight loss
(89%), fever (88%) and diarrhoea (86%).
(Fig.4 and 5)
6. HIV is prevalent in all the parts of the
country, though distribution is
heterogeneous.

J&K

Himachal Pradesh
Punjab
Chandigarh

Haryana Delhi
Arunachal Pradesh
Sikkim
Rajasthan Uttar Pradesh
Assam
Nagaland
Meghalaya
Bihar Manipur
Tripura
Madhya Pradesh Mizoram
Gujarat
West Bengal

Daman & Diu

Dadra Nagar Haveli Orissa
Maharashtra
>1% In Antenatal mothers

>5% In High Risk Groups

Andhra Pradesh
Goa <5% In High Risk Groups
Karnataka Pondichery

Tamil Nadu Andaman & Nicobar

Lakshwadeep Kerala

Fig. 1. Adult HIV prevalence in 2002 in India

9
Indian Journal of Practical Pediatrics 2003;5(4)280

50000

45000
Number of AIDS cases

40000

35000

30000

25000

20000
No. of AIDS cas es
15000

10000

5000

0
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Year
Fig.2. Cumulative number of AIDS cases in India - December 2002

89 86 88
Heterosexual 72
2.14 68
Percentage

3.27 IDUs 3.36%

6.7
3.36 28
Blood & blood
Products 3.27%
Perinatal 2.14%
84.5 Wt. Loss diarrhoea fever Asthenia Cough PGL

History NA 6.7% Fig. 4. Presenting signs and symptoms of

AIDS cases in India, December 2002
Fig. 3. Mode of transmission in AIDS cases 65 57.5
in India : December 2002
Percentage

36
7. HIV is now spreading from high risk
behaviour groups to general population, as 3.8 0.6
8
well.
PCP
Cryptococcus
TB

Kaposi

Others
Candidiasis

8. HIV is spreading from urban to rural areas.

9. More and more women attending ante-natal
clinics are testing positive, thus with the
added risk of perinatal transmission, more Fig. 5. Opportunistic Infections in AIDS
children may be HIV infected cases in India : December 2002
10

10. Highest number of infection are reported to
occur through the sexual contact.
11. About 89 percent of the reported cases are
from the sexually active age group of 15 -
49 years.
12. Migration and mobility has increased the
chance of the disease spreading to other
areas/persons.
13. The social stigma attached to sexually
transmitted infections also holds good for
HIV/AIDS with more disastrous
consequences.
Mode of HIV Transmission
Epidemiological studies throughout the
world have shown three modes of HIV
transmission. In adults 2/3 of the transmission
occurs by hetro-sexual route, whereas in children,
mother to child transmission is the predominant
mode.
Mother - to- child transmission: HIV-infected
woman can transmit HIV to her foetus or infant
before, during, or after birth. A pregnant woman
with HIV infection has an approximately 30%
chance of passing the virus to her foetus or
newborn baby. There is evidence that infection
can occur as early as the first 12-15 weeks of
gestation. 60% of perinatal infections are in utero
or during the birth process. It is estimated that
40% of perinatal infections occur through breast-
feeding.
Blood-borne infection: HIV-infected blood,
blood products, transplanted organs or tissues and
the use of improperly sterilized needles and
syringes that have been in contact with infected
blood can transmit HIV. This is the most efficient
way of transmission of HIV. Even a small
transfusion of infected blood results in virtually
100% seroconversion.
Sexual Route : Heterosexual or homosexual
contact, is the major route of transmission. HIV
11
2003;5(4)281
can be transmitted through any individual act of
unprotected sexual intercourse, that is, any
penetrative sexual act in which a condom is not
used where one partner is infected with HIV.
Male-to-male sex occurs in all countries of the
region and features significantly in the epidemic.
Countries that have measured HIV prevalence
among men who have sex with men have found
it to be high
Throughout the region, injectable drug use
drug use offers the epidemic huge scope for
growth. About 50% of injecting drug users
already have acquired the virus in parts of
Malaysia, Myanmar, Nepal, Thailand and in
Manipur in India, while HIV infections among
Indonesias growing population is increasing.
Despite sweeping epidemics among injecting
drug users, minimum services that can protect
those drug users against HIV infection are not
available in most of the region.
Issues in children
The epidemiological profile of HIV/AIDS
in children in our country has not been clearly
defined. As more and more women are being
infected, the number of children born with HIV
infection is increasing. It is estimated that 25
million pregnancies occur annually in India. With
a prevalence of HIV around 1% in antenatal
mothers.25, 000 children may be born every year
with HIV infection. Children in households beset
by illness and lack of food are severely affected.
As parents fall ill and die, family burdens shift to
the children. For many, neither money nor time
is available for normal schooling to be continued.
Opting out of school may help with cash needs
over the short term but, in the long term, it
entrenches the households poverty and puts the
children at greater risk of becoming infected with
HIV. The result is a vicious circle linking poverty,
food insecurity and HIV/AIDS. . It is estimated
that about 1,20,000 children orphaned by AIDS
epidemic are living in India. The responsibilities
Indian Journal of Practical Pediatrics
of looking after younger brothers and sisters fall
on the young shoulders of the eldest child in the
family. There is a danger that orphaned children
are ostracized or abused and their property rights
trampled upon by their relatives. They face
rejection, exclusion and discrimination. They
tend to suffer from non- fulfilment of their
nutritional, emotional and educational needs.
These facts emphasize that Pediatric AIDS is not
only a medical illness but also a psychological
and social issue.
Conclusion
The future trajectory of the global HIV/
AIDS epidemic depends on whether the world
can protect young people everywhere against the
epidemic and its aftermath.
Just as certain sectors of society are at
particular risk of HIV infection, certain conditions
favour the epidemics growth. As the current food
emergencies in southern Africa show, the AIDS
epidemic is increasingly entangled with wider
humanitarian crises. The risk of HIV spread often
increases when desperation takes hold and
communities are wrenched apart. At the same
time, the ability to stall the epidemics growth
also suffers, as does the capacity to provide
adequate treatment, care and aupport.
It is vital that HIV/AIDS-related activities
become an integral part of wider-ranging efforts
to prevent and overcome humanitarian crises.
Given that many of the factors facilitating HIV
transmission (including periodic economic
CONTRIBUTORS TO CORPUS FUND OF IJPP
Rs. 1000/-
Dr. Pramod Gulati, Jhansi, Uttar Pradesh,
Dr. Y.N. Pattabhi, Hassan, Karnataka
Dr. N. Raghavan, Trichy, Tamilnadu.
12
2003;5(4)282
upheaval and high rates of population mobility)
are rife throughout this region, no country is
immune to a rapidly spreading and wide-scale
epidemic. Most countries, though, still have a
window of opportunity for mounting and
sustaining HIV/AIDS initiatives that could avert
such an outcome. A major challenge for India
now is that of rapidly expanding the awareness
and preventive programmes to all vunerable
groups including the illiterate population and the
rural community especially the women and
adolescents.
Bibliography
1. UNAIDS (Joint United Nations Programme on
HIV/AIDS), AIDS epidemic update,
December, 2002.
2. Combating HIV/AIDS in India National
AIDS Control Organisation, Ministry of Health
and Family Welfare, Government of India,
2001.
3. Data supplied by National AIDS Control
Organisation, Ministry of Health and Family
Welfare, Government of India, 2003.
4. Specialists Training & Reference Module on
HIV/AIDS, National AIDS Control
Organisation, Ministry of Health & Family
Welfare, Govt. of India, 2003.
5. UNAIDS/UNICEF/UNFPA/WHO Inter-
Agency Task Team on the Prevention of
Mother-To-Child Transmission of HIV.
Preventing mother-to-child HIV transmission:
Technical Experts recommend use of
antiretroviral regimens beyond pilot projects
Experts say benefits outweigh potential adverse
effects. UNAIDS Press Release 25/10/2000.
Dr. Rema Chandramohan, Chennai, Tamilnadu.
Dr. M. Sundaramurthy, Dharmapuri, Tamilnadu.
Dr. Arun Kumar. Sahu, Samastipur, Bihar.

HIV INFECTION
IV DRUG ABUSE AND HIV IN
NORTH-EASTERN INDIA
* Brajachand Singh Ng
** Chourjit Singh Ksh
Abstract: Heroin and intravenous drug users
constitute a special health risk group in view of
their predilection to develop HIV infection and
AIDS through sharing of needles and unprotected
sexual intercourse. The states mainly affected by
this risk group are Manipur and Nagaland and
to a lesser extent, Mizoram, Meghalaya and other
States of North Eastern India.
Keywords: Intravenous drug abuse, HIV North-
Eastern India
Introduction
By the end of 2002, forty two million people
had been infected with HIV and by the end of
1999, twenty one million people had died of
AIDS. In India alone, 3.97 million people had
been infected with the virus and the country has
the largest number of people living with HIV,
next to South Africa. According to the National
AIDS Control Organization (NACO), 6.7% of
the HIV infections in India are attributable to
Injecting Drug Use (IDU) route of transmission.
Sharing of infected needles for injecting drugs
and unprotected sex makes Injecting Drug Users
(IDUs) vulnerable to HIV and in turn, makes
them core transmitters of the virus, transmitting
* Professor and Head, Department of
Microbiology
** Professor of Pediatrics
Regional Institute of Medical Sciences,
Lamphelpat, Imphal-795001
13
2003;5(4)283
the virus to the general population. In India, the
epidemic of HIV among IDUs started in Manipur.
There has been speculations on how the HIV/
AIDS epidemic has spread so rapidly among the
IDUs in Manipur compared to other North East
states of India, i.e. Assam, Meghalaya, Mizoram
and Nagaland.
Manipur
Manipur is geographically very close to the
notorious Golden Triangle (between Myanmar,
Thailand and Laos) where more than 20% of
worlds heroin drug is reportedly produced. Due
to proximity to the Golden Triangle with
perforated borders, Manipur became an
alternative route for illegal international drug
trafficking in the late seventies and early eighties.
Soon, Manipur became a User State by early
eighties. Pure heroin which is the injectable form,
locally known as No 4 is easily available. The
problem of Heroin addiction reached an
explosive situation in 1984 when many gruesome
murders connected with drug occurred in the
state. 1
The first positive case was, reported by the
Government in February 1990. As of March
2003, a total of 15,043 HIV positive cases (2,253
females) and 1,998 AIDS cases (290 deaths) were
reported out of 95, 256 blood samples screened,
giving a seropositivity rate of 157.92 per 1000
blood samples screened.2 Manipur, with hardly
0.2% of Indias population is contributing to
nearly 8% of Indias total HIV positive cases.
In a study conducted by ICMR in
Manipur in 1991, all the 450 drug users
interviewed used injectable heroin. They were
Indian Journal of Practical Pediatrics
predominantly (95%) male. The age range of the
IDUs was found to be between 12 and 35 years.
Peer pressure and curiosity were the most
common reasons cited for initiating heroin use.
It was reported that females comprised about 5 -
8% of injecting drug users, even though their
numbers were increasing.3 The occupational
distribution of IDUs revealed that 53% of them
were unemployed including 34% who were
students. Most of the IDUs were staying with
their families, who were trying to cope with social
and economic pressures thus created within the
home. The educational status of the IDU problem
population was quite high. 4
Nagaland
In 2001, the prevalence of HIV among the
IDUs was 6.5% and among the STD clinic
attendees, it was 7.4%. The prevalence of HIV
in the antenatal population in 2001 was 1.25%.
According to NACOs classification, Nagaland
falls under the category of high HIV prevalent
states. ICMR estimated the size of the IDU
population in Nagaland as 1500 in 1992 - 93,
nearly ten years back.5 Different individuals and
NGOs working with IDUs in the state as well as
other parts of India have their own guestimates,
ranging from 5,000 to 20,000.
Meghalaya
Testing for HIV in Meghalaya began in the
year 1990. The first seropositive case was
detected in the year 1990. Upto the year 2002,
17,664 samples were screened, of which 62 tested
positive for HIV; 10 cases of AIDS have been
reported. Out of the 62 people tested positive for
HIV upto March 1998, 13 were blood donors,
15 were IDUs, 3 were STD patients, 1 antenatal
woman, 2 suspected AIDS cases and 28 others.
The spouses of four of the seropositives were also
found to be infected with HIV.6 The estimated
HIV prevalence among IDUs measured in the
Sentinel Sites for IDUs was 1.41% in 20007.
14
2003;5(4)284
Mizoram
According to the State AIDS Control
Society, 29,870 blood samples were screened till
March 1998 and 96 were found seropositive for
HIV. In the study conducted by ICMR in 1991,
HIV prevalence among IDUs in the state was
found to be 8 - 10%. In a study at the Surveillance
Center of Regional Medical College (presently
Regional Institute of Medical Sciences), Imphal
till the end of 1991,1.5% of the 1000 samples
from Mizoram were positive for HIV and 80%
of the HIV positives were IDUs6. In the 2000
round of the Sentinel Surveillance, the HIV
prevalence among STD clinic attendees at Aizawl
site was 2%. Among the women attending ANCs,
the HIV prevalence was 0.37% during 20007.
Assam
Screening for HIV in Assam was started by
Gauhati Medical College (GMC) and Indian
Council of Medical Research in 1988 and 12
samples were found to be seropositive out of
11,352 samples tested for HIV. The first AIDS
case in the state was detected in 19906. 1n 2000,
the prevalence of HlV among STD clinic
attendees was 0.61 % and in 2001, it was 1.49%.
The prevalence of HIV in the antenatal
population in 2000 and 2001 was 0%. There is
no surveillance of HIV among IDUs in Assam.
According to NACOs classification, Assam falls
under category of low prevalence states7. The
study by the Regional Medical Research Centre
found that the prevalence of HIV infection in
Assam was at a lower level than the rest of the
country and at a much lower level than the
neighbouring states of Manipur and Nagaland.
Between January 1990 and May 1993, the
Regional Medical Research Centre, Dibrugarh
undertook HIV screening in upper Assam. 1992
were tested from general population (501 tea
garden labourers and 1491 oil industry
employees) and none were found seropositive.

In another study among different high risk
groups, 9350 samples were screened and nine of
the samples were found seropositive. Of the ones
who tested HIV positive, two were recipients of
blood transfusion, two were IDUs from
Nagaland, and five were from floating
population, temporarily residing in Assam, with
history of heterosexual promiscuity6. The NACO
behavioral survey study conducted in Assam in
2002 has reported that 2.2% of the clients of sex
workers in Assam have reported injecting in the
past 12 months.7
Intervention for injecting drug users
The basic message for prevention of HIV
infection among the injecting drug users are :
1. Total abstinence from drugs Say No to
Drugs and Yes to Life.
2. If you cannot do that, use orally and do not
inject. You should use legal and less harmful
drugs like Buprenorphine instead of more
harmful and illegal drugs like heroin.
3. If you cannot give up injecting drugs, you
should not share needles and syringes with
others in all situations.
4. If you have to share needles and syringes
under some compelling circumstances, then
you should sterilize needles and syringes
with 5% bleach with the standard
sterilization procedure. The strategy is based
on Harm Reduction or Harm
Minimization. In order to ensure effective
implementation of the Harm Reduction
Programme in Manipur, the programme is
integrated with care component and it is
called Rapid Intervention and Care
15
2003;5(4)285
(RIAC) Project. Manipur is the first state in
India to have adopted Harm Reduction
Programme.
Research needs:
1. To carry out community prevalence of
Sexually Transmitted injection (STI) / HIV
2. To address cross border drug trafficking
3. To carry out behaviour survey among IDUs
4. To focus attention in youth and adolecents
References
1. Status report: National AIDS Control
Programme, Manipur, published by Manipur
State AIDE; Control Society, Imphal, 2002 -
2003, 1 - 2.
2. Epidemiological analysis of HIV/AIDS in
Manipur, published by Manipur State AIDS
Control Society,2003,1.
3. NACO, Ministry of Health and Family Welfare,
National Baseline High Risk and Bridge
Population Behavioral Surveillance Survey,
2002, Part 2 (Men who have sex with men and
Injecting Drug Users).
4. Sarkar S, P. Mookerjee, A. Roy, T.N. Naik, J.K.
Singh; Descriptive Epidemiology of
intravenous heroin users - a new risk group for
transmission of HIV in India, Journal of
Infection,1991,23, 201 -207.
5. ICMR Report on the project: ICMR unit for
research on AIDS in NE States of India ( 1992-
1995).
6. Situational analysis of HIV and Drug Abuse in
North-Eastern Region of India; published by
Regional Medical Center, ICMR, 1998.
7. NACO, Combating HIV/AIDS in India,
published by Ministry of Health & Family
Welfare, 2000 - 2001.
Indian Journal of Practical Pediatrics
HIV INFECTION
CLINICAL MANIFESTATIONS OF
HIV INFECTION IN CHILDREN
* Rakesh Lodha
* Kabra SK
Abstract : Most of HIV-infection in children are
vertically transmitted i.e. acquired from mothers.
Blood and blood products, however, remain an
important source and are responsible for
infection in 10 30 % of total cases in the
developing countries. Approximately 10 to 20%
of infants experience rapid progression of disease
and die of AIDS related complications by 4 years
of age. The mean survival time for the remaining
80-90% infected children is approximately 9-10
years
Clinical manifestations depend on the
severity of immunosuppression. These in the
initial stages may be nonspecific and consist of
failure to thrive, recurrent fever, diarrhoea, and
respiratory infections. Children may have
hepatosplenomegaly, lymphadenopathy,
neurological manifestation and recurrent
bacterial infections.
Co-existent tuberculosis (TB) and HIV
infections accelerate the progression of both the
diseases. HIV infected children are more likely
to have extra-pulmonary and disseminated
tuberculosis; the course is also likely to be more
rapid. The relative risk of active tuberculosis in
children infected with HIV is at least 5 to 10 fold
higher than that in children not infected with HIV.
* Department of Pediatrics
All India Institute of Medical Sciences
Ansari Nagar, New Delhi 110029
16
2003;5(4)286
Apart from infections, other manifestations
include progressive encephalopathy (PE),
cardiovascular problems including left
ventricular dysfunction, lymphocytic interstitial
pneumonitis (LIP), anemia, neutropenia,
absolute or relative lymphopenia, thromb-
ocytopenia, and eosinophilia, rheumatological
manifestations such as biphasic Raynauds
syndrome, necrotising vasculitis, lip necrosis,
livedo reticularis, knee arthalgia, vasculitis, and
septic arthritis.
Clinical case definition of HIV infection
given by WHO includes combination of symptoms
and signs and has poor sensitivity but good
specificity. One should suspect HIV infection in
a child who presents with symptoms described
in category C of CDC, has specific illness like
LIP, has atypical manifestations of common
illnesses, presents with combination of symptoms
or born to HIV positive parents.
Key words: Pediatric HIV, AIDS, Clinical
manifestations.
A syndrome of immune deficiency with
opportunistic infections was first described in
1982 and the first publication of HIV/AIDS in
children appeared in 1983. At the end of 2002, it
is estimated a total of 42 million individuals were
infected globally, of which 3.2 million (7.6%)
were children below 15 years of age. Ninety five
percent of the infected individuals are in the
developing countries. Of the 3 million deaths due
to HIV in 2001, 0.6 million (20%) occurred in
children below 15 years. Disproportionately
higher mortality in children suggests a more
aggressive course in children. The estimated
number of people living with HIV/AIDS in India

by the end of 2001 were 3.97 million, of which
0.17 million (4.3%) were children below 15
years1.
Modes of transmission
Most of the infections in children are
vertically transmitted i.e. acquired from mothers.
Blood and blood products, however, remain an
important source and are responsible for infection
in 10 30 % of total cases in the developing
countries2. Some of the mothers also acquire HIV
through blood transfusion and transmit the
infection to their babies3.
Natural history of vertically transmitted HIV
infection.
The clinical course of vertical HIV-1
infection is highly variable, but before the
widespread use of antiretroviral therapy, two
general patterns of survival were described.
Approximately 10% to 20% of infants
experienced rapid progression of disease and died
of AIDS related complication by 4 years of age.
The mean survival time for the remaining 80-
90% infected children was approximately 9-10
years4. In a cohort of infants followed from birth,
by 12 months of age 83% had shown some sign
of HIV disease, 74% had progressed to category
A, 55% to category B, 21% to category C and
6% to death5. Hepatomegaly and lymphadeno-
pathy were the most common category A signs
during first 6 months of life. In another cohort
study, category C events or deaths were estimated
for 20% of perinatally infected infants in the first
year of life, with approximately 5% succumbing
per year thereafter6.
Analysis of data from Pediatric Spectrum
of Disease project in the USA showed that the
mean time spent by perinatally infected children
in each stage were: N, 10 months; A, 4 months;
B, 65 months; and C, 34 months4. In this study, it
was estimated that a child born with HIV
17
2003;5(4)287
infection had a 50% chance of severe signs or
symptoms by 5 years of age, and a 75% chance
of surviving to 5 years of age. The estimated
mean time from birth to stage C was 6.6 years,
and the estimated mean survival time was 9.4
years. This study highlighted that perinatally
infected children progress to moderate symptoms
in the second year of their life and then remain
moderately symptomatic for more than half of
their expected life span. This clearly underscores
the need for their clinical care before the onset
of AIDS.
In an African study, the estimated risk of
death among perinatally infected children at 2
and 5 years of age was 45% and 62%
respectively; the median survival time was 12.4
months7. This study observed that early infection,
early onset of HIV-related conditions, failure to
thrive, and generalized lymphadenopathy were
associated with subsequent risk of death, whereas
LIP was predictive of a milder illness. Thus the
prognosis appears to be poorer in the African
children. There are no Indian data to describe the
natural history of HIV infection in Indian
children.
The available pediatric data is in contrast
with data from adults that link disease expression
and survival with viral load or immuno-
suppression in each individual. In children the
disease progression is much faster than in adults.
Clinical manifestations
Clinical manifestations depend on the
severity of immunosuppression. These in the
initial stages may be nonspecific and consist of
failure to thrive, recurrent fever, diarrhoea, and
respiratory infections. Children may have
hepatosplenomegaly, lymphadenopathy,
neurological manifestation and recurrent
bacterial infections. In contrast to adults who
present more frequently with distinct HIV-
associated conditions, infected children in
Indian Journal of Practical Pediatrics 2003;5(4)288

Table 1. Clinical features in HIV infected children

Tovo et al 92 8 Italian Register for HIV infection 9410
(n=285) (n=22) (n=22)
Failure to thrive 49.9% 49% 78%
Fever 43% 42% 71%
Diarrhea 30.9% 31% 50%
Hepatomegaly 86.8% 84% 83%
Lymphadenopathy 78% 91% 58%
Splenomegaly 75.3% 75% 76%
Neurological invl. 23.8% 11% 58%
LIP 13.9% 17% 20%
Recurrent serious bacterial
infections 12.7% 15% 26%

Table 2. Clinical features in HIV infected African children (figures in %)11

Rwanda Zaire Zimbabwe Uganda Nigeria
(n=107) (n=201) (n=190) (n-755) (n=63)
Wt. Loss/FTT 89 97 54 80 50.8
Chr. diarrhea 83 62 25 66 38
LRTI 70 61 41 49 31
Chr. Fever 58 85 NA 71 50.8
Lymphadenopathy 91 24 65 31 58.7
Hepatomegaly 66 52 31 NA 19
Oral Thrush 40 NA 18 55 19
Neurological NA 18 NA 3 9.5
Recurrent infection NA NA 41 17 NA

developing countries commonly present with a reconstitution following institution of anti-

disease spectrum that is similar to uninfected
children 3, 8-14 (Table 1-3).
The Centre for Disease Control and
Prevention (CDC), USA has classified clinical
features of Pediatric HIV infection into 4 clinical
categories for children below 13 years of age14.
Once classified, a child cannot be reclassified into
a less severe category even if the childs clinical
status improves such as in the case of immune
18
retroviral therapy or resolution of clinical event.
1. Category N, describes asymptomatic
children without signs or symptoms
considered to be the result of HIV infection
or who have only one of the conditions listed
in category A.
2. Category A: Children classified as category
A should have two or more mild symptoms
 2003;5(4)289

Table 3. Clinical features in HIV infected Indian children

Clinical features Merchant et al 12 Lodha et al 3 Dhurat et al13
(n=285) (n=22) (n=22)
Failure to thrive (FTT) 45.6 100 48.6
Recurrent/ Persistent pneumonia 8.4 86.3 24.3
Chronic/ recurrent diarrheoa 15.1 45.5 27.2
Lymphadenopathy 23.5 40.9 35.1
Hepatomegaly 81.8 51.9
Oral candidiasis 14.3 36.4 48.6
Splenomegaly 63.6
Hepatosplenomegaly 28.8 67.5
Tuberculosis 29.5 59.1
CNS involvement 4.6 13.6
Bronchiectasis 9.1
Asymptomatic 16.8
Figures are in %.

of HIV related conditions such as:
lymphadenopathy, hepatomegaly,
splenomegaly, dermatitis, parotitis, recurrent
upper respiratory infections, sinusitis, otitis
media. Children with category B or C clinical
conditions do not remain in category A, even
if they have multiple category A conditions.
3. Category B defines children who are
moderately symptomatic with HIV related
conditions. These include anemia,
neutropenia or thrombocytopenia persisting
for more than 30 days; single episode of
bacterial meningitis, pneumonia, or sepsis;
CMV infection before 1 month of age;
hepatitis; recurrent or chronic diarrheoa;
lymphoid interstitial pneumonia (LIP);
disseminated varicella zoster virus
infections. Inclusion in category B can occur
only in the absence of category C conditions.
4. Category C conditions, with the exception
of LIP, are AIDS defining conditions. These
19
include recurrent severe bacterial infection
(meningitis, pneumonia, septicemia, etc.),
esophageal/pulmonary candidiasis,
cryptosporidiosis, CMV disease at >1 month
of age, disseminated/extra pulmonary
mycobacterial tuberculosis, pneumocystis
carinii pneumonia (PCP), HIV-
encephalopathy.
This classification system provides a useful
guideline for pediatricians to evaluate HIV
progression in children. In addition, it serves as
a standard for researchers world wide to measure
the importance of clinical events and in drug
trials.
Apart from clinical manifestation the
severity of illness can be assessed by CD4 cell
counts in blood 14. Lymphocyte counts and their
subgroups depend on age and the cut-off values
are different from adults. Status of immunologic
function based on CD-4 counts according to age
is given in Table 4.
Indian Journal of Practical Pediatrics
Table 4. Immunologic categories based on age specific CD-4 T Lymphocyte
counts.
Age of Child
Immunologic <12 mo
categories
Cells/mm3 .%
1. No evidence
of Suppression > 1500 > 25
2. Moderate
Suppression 750-1499 15-24
3. Severe
Suppression >750 <15
Some of the conditions are described in
detail in the following sections.
Recurrent bacterial infections 15,16
There is failure of both cell mediated and
humoral immunity. Despite hypergamma
globulinemia, these children are at risk for severe
and recurrent bacterial infections. There is delay
in clearing of infections caused by the usual
pathogens. Serious bacterial infections include
bacteremia, meningitis, pneumonia,
osteomyelitis, septic arthritis, and abscesses at
various sites. Bacteremia is the most common
laboratory-documented serious bacterial
infection. Acute pneumonia is the most common
clinically diagnosed severe bacterial infection. In
various Indian studies, up to 90% of HIV-infected
children had history of recurrent pneumonias.
Initial episodes of pneumonia often occur before
the development of significant immuno-
supression. As the immunosupression increases
the frequency increases. The common pathogens
for community-acquired pneumonia in these
children are Streptococcus pneumoniae,
Haemophilus influenzae, and Staphylococcus
aureus. However in children with severe
immunosupression and in hospital-acquired
infections, gram negative organisms, such as,
20
2003;5(4)290
1-5 yrs 6-12yrs. %
Cells/mm3 % Cells/mm3 %
> 1000 > 25 > 500 > 25
500-999 15-24 200-499 15-24
<500 <15 <200 <15
Pseudomonas aeruginosa gain importance.The
clinical features of pneumonia in HIV-infected
children are similar to those in uninfected
children. However, in severely immuno-
compromised children, the signs may be subtle.
Often, the response to therapy is slow and the
relapse rates are high. Bacteremia may be more
common, seen in up to 50%. Sinusitis is the
second most common clinically diagnosed
bacterial infection in HIV-infected children. The
clinical presentation is similar to those of
immunocompetent children. A history of nasal
discharge and persistent cough for more than two
weeks should prompt suspicion of sinusitis in
HIV-infected children. The prevalence of
meningitis, osteomyelitis, septic arthritis,
pericarditis and cellulitis does not appear to be
unusually high. The pathogens for these
infections are the same as those isolated from
immunocompetent children; the clinical features
are also similar. In addition, these children are
prone to develop various minor bacterial
infections; the clinical features are similar to
immunocompetent children.
Tuberculosis 17,18
With the spread of the HIV infection, there
has been resurgence in tuberculosis. The two

diseases have significantly detrimental
interactions. Co-existent TB and HIV infections
accelerate the progression of both the diseases.
HIV infected children are more likely to have
extra-pulmonary and disseminated tuberculosis;
the course is also likely to be more rapid. An HIV
infected child with tubercular infection is more
likely to develop the disease than a seronegative
child. The overall relative risk of active TB in
children infected with HIV is at least 5 to 10 fold
higher than that in children not infected with HIV.
In the absence of significant immunosupression,
the clinical manifestations are not much different
from that in seronegative children. In patients
with low CD4 counts, the pulmonary lesions are
more extensive. Mediastinal adenopathy is also
more frequently seen. Pleural effusions are
uncommon. Diagnosis of TB in infected children
poses greater challenges than in other children.
Even with the use of a lower cut-off of 5 mm, the
tuberculin test is often negative, particularly in
children with severe immunosupression. In
extensive disease, the bacteriological
confirmation rates are likely to be greater. All
attempts should be made to isolate
Mycobacterium tuberculosis. Other than
providing definitive diagnosis, it offers the
opportunity to do sensitivity analysis. The
incidence of multi-drug resistant tuberculosis is
higher in HIV infected patients.
Infection with Mycobacterium avium-
intracellulare (MAI) 19
Pulmonary disease with MAI is uncommon
in children with HIV infection, despite
immunosuppression. The common symptoms
and signs include: persistent fever, failure to
thrive, night sweats, lymphadenopathy,
organomegaly, and refractory anemia. The
pulmonary lesions are usually limited to
lymphadenopathy and localized parenchymal
lesions. The diagnosis of disseminated disease
primarily depends on isolation of the organism
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2003;5(4)291
from blood. Current therapy for disseminated
MAI infection includes the use of a combination
of clarithromycin or azithromycin with
ethambutol.
Pneumocystis carinii pneumonia 19,20
PCP is the most common opportunistic
infection in HIV-infected children. However,
there is lack of data from India to define the
magnitude of the problem. The data from Africa
show a low incidence of PCP. Children with PCP
are more sick than the adults with this infection.
The case fatality rates are also higher. In 1992,
the estimated median survival after diagnosis of
PCP, was 19 months. The onset may be acute in
infants. Older children are more likely to have a
more indolent and protracted course. The clinical
manifestations include tachypnea, dyspnea and
fever. The examination of the chest is
unremarkable except for tachypnea and
retractions. Asymmetric breath sounds,
crepitations and rhonchi are uncommon. The
chest radiograph commonly reveals diffuse
interstitial lung disease without hilar adenopathy.
Other patterns include localized infiltrates,
hyperinflation, and non-cardiogenic pulmonary
edema. The radiograph may be normal in less
than 5% children. Hypoxemia is the hallmark of
PCP. A markedly elevated (A-a)DO2 and a high
serum LDH level are often seen.
The diagnosis of PCP begins with the
suspicion. The diagnosis requires demonstration
of cysts or organisms in lung secretions or tissue.
Induced sputum, nasopharyngeal swab and BAL
are feasible techniques to detect Pneumocystis
carinii. Various stains can be used for detection:
1) Stains for the organism such as Giemsa stain,
2) Cyst wall stains such as Gomoris
methenamine-silver nitrate, toluidine blue
Ostain, and 3) immunospecific stain which stains
both the trophozoites and cysts. The latter
technique may provide a far more accurate and
specific diagnosis of PCP. However, it is time
Indian Journal of Practical Pediatrics
consuming. PCR has also been used for detecting
the organism in respiratory secretions.
Viral infections19
In children with AIDS, disseminated CMV
is a known opportunistic infection, but
pneumonia is rare. Prospective data showed that
when HIV-infected children develop respiratory
syncytial virus disease, they are less likely to
wheeze and more likely to have pneumonia and
prolonged shedding of the virus. Infections with
influenza, herpes simplex and varicella viruses
have been reported but are uncommon.
Fungal infections 19
Fungal infections especially invasive
infections are also seen more frequently. These
include candidiasis, cryptococcosis,
histoplasmosis and aspergillosis. Mucosal and
cutaneous fungal infections are more commonly
seen than systemic infections. Most HIV-infected
children develop oral candidiasis at least once.
These children are also at an increased risk of
esophageal candidiasis. Pulmonary fungal
infections usually present as a part of
disseminated disease in immuno-compromised
children. Primary pulmonary fungal infections
are uncommon. Pulmonary candidiasis should be
suspected in any sick HIV-infected child with
lower respiratory tract infection that does not
respond to the common therapeutic modalities.
A positive blood culture supports the diagnosis
of invasive candidiasis. Aspergillosis is an
uncommon infection in HIV-infected children.
Invasive disease is common in these children. It
usually presents as persistent pneumonia
associated with atelectatic or large apical
cavitatory lesions. Pneumothorax is common.
Diagnosis of invasive bronchopulmonary
aspergillosis must be considered in a child with
compatible clinico-radiologic picture and
recovery of organism in pure culture from BAL,
if other causes are excluded. In children with
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2003;5(4)292
advanced HIV infection, the disease runs an
aggressive course. Cryptococcosis commonly
presents as a subacute meningitis or
meningoencephalitis; many children may present
with nonspecific, subtle symptoms, including
fever and headache. Pulmonary involvement may
be seen in half of these children. However,
isolated pulmonary cryptococcosis is not
commonly seen. Other uncommonly reported
fungal infections include histoplasmosis and
coccidioidomycosis.
Lymphoid interstitial pneumonitis (LIP)21
LIP has been recognized as a distinctive
marker for pediatric HIV infection and is included
as a Class B condition in the revised CDC criteria
for AIDS in children. While the prevalence in
HIV infected children in the west has been
reported to be around 20%, figures from Africa
suggest that it is not common. The etiology and
pathogenesis of LIP are not well understood.
Suggested etiologies include: an exaggerated
immunologic response to inhaled or circulating
antigens, and/ or primary infection of the lung
with HIV, Ebstein-Barr Virus, or both. There is
evidence to suggest that EBV plays significant
pathogenetic role in LIP. LIP is considered to
reflect the local response to persistent antigenic
stimulus. This stimulus could be EBV, which is
a potent, polyclonal stimulator for B cells.
Primary infection with HIV may be directly
responsible for LIP. LIP is more common in
children with perinatally acquired HIV infection
than in children who acquire the infection by
other route. This may be due to direct intrauterine
or intrapartum exposure of lung tissue to HIV. It
is likely that LIP represents primary infection of
the lungs. Subsequent histopathologic and clinical
expression of the disease may be driven by
postnatally acquired primary EBV infection. LIP
is characterized by nodule formation and diffuse
infiltration of the alveolar septae by lymphocytes,
plasmacytoid lymphocytes, plasma cells and

immunoblasts. There is no involvement of the
blood vessels or destruction of the lung tissue.
Children with LIP have a relatively good
prognosis compared to other children who meet
the CDC surveillance definition of AIDS. LIP is
usually diagnosed in children with perinatally
acquired HIV infection when they are older than
1 year of age. In contrast, PCP is diagnosed
typically in the first year of life. Most children
with LIP are asymptomatic. Tachypnea, cough,
wheezing and hypoxemia are usual signs of fully
expressed disease; crepitations are uncommon.
Clubbing is often present in advanced disease.
These patients can progress to chronic respiratory
failure. Long standing LIP may be associated with
chronic bronchiectasis. The presence of a
reticulonodular pattern, with or without hilar
lymphadenopathy, that persists on chest
radiograph for 2 months or greater and that is
unresponsive to antimicrobial therapy is
considered presumptive evidence of LIP. Care
should be taken to exclude other possible
etiologies. A definitive diagnosis of LIP can only
be made by histopathology.
Diarrhoea 22, 23
Diarrhoea acute, recurrent and persistent
is a common disorder in HIV infected children.
In a HIV child, infection with any enteropathogen
can result in prolonged diarrhea and
malabsorption with subsequent malnutrition. The
etiologic agents for diarrhea in HIV infected
children include the common enteropathogens,
C. jejuni, Helicobacter cinaedi, Shigella and
cryptosporidium. Cryptosporidium is associated
with voluminous profuse watery diarrhea,
anorexia, weight loss and even death in HIV
infected individuals. Stool contains mucus but
no blood or leukocytes. Diarrhea may also be due
to systemic infection with atypical mycobacteria,
CMV, HIV enteropathy, drugs or bacterial
overgrowth. The risk of persistant diarrhea is
increased especially with cryptosporidium.
23
2003;5(4)293
HIV encephalopathy 21,24
Human immunodeficiency virus type-1
(HIV-1)-associated neurologic disease, known as
HIV-1-associated progressive encephalopathy
(PE), is a common concomitant in the progression
towards AIDS. PE, characterized by a triad of
symptoms including impaired brain growth,
progressive motor dysfunction, and loss or
plateau of developmental milestones, is believed
to result from both direct and indirect effects of
HIV-1 infection on the central nervous system
(CNS). Consequent to the hallmark systemic
immune deficiency of HIV infection, the CNS
becomes susceptible to opportunistic infections,
which add further morbidity and mortality, and
may contribute either directly or indirectly to
neurologic symptoms which can often mimic PE.
Static encephalopathies (SE) represent fixed,
nonprogressive neurologic or
neurodevelopmental deficits in HIV-infected
children. SE may or may not be caused by HIV
infection but are often associated with such
identifiable insults as prematurity, in utero
exposure to toxins or infectious agents, or head
trauma. Additional neurological manifestations
of HIV infection are seizures, cerebrovascular
complications (i.e., stroke), myelopathies,
neuromuscular syndromes, and CNS
complications of opportunistic infections.
Neurobehavioral aberrations have also been
observed in pediatric HIV infection.
Cardiomyopathy25
Cardiovascular problems associated with
HIV infection including left ventricular
dysfunction and increased left ventricular mass
are common and clinically important indicators
of survival for children infected with HIV. A
prospective multicenter cohort study has
evaluated 205 vertically HIV-infected children
enrolled at a median age of 1.9 years, 600 HIV-
exposed children enrolled prenatally or as
Indian Journal of Practical Pediatrics
neonates, of whom 93 were ultimately HIV-
infected. The main outcome measures were
echocardiographic indices of left ventricular
dysfunction. Left ventricular dilatation, heart
failure, and/or the use of cardiac medications
were more common in infected compared with
uninfected children. The mortality rate 1 year
after the diagnosis of heart failure was 52.5%
[95% CI, 30.5-74.5]. Authors concluded that
cardiac dysfunction occurred in 18% to 39% of
HIV-infected children and was associated with
an increased risk of death. They have
recommended that HIV-infected children should
undergo routine echocardiographic surveillance
for cardiac abnormalities. Zidovudine-induced
cardiomyopathy has also been reported21.
Hematological manifestations 21
Hematological manifestations in pediatric
HIV infection include anemia, neutropenia,
absolute or relative lymphopenia, thrombocytop-
enia, and eosinophilia. Severe thrombocytopenia
and anemia are correlated with poor prognosis.
These abnormalities may occur because of
peripheral destruction of blood elements, HIV
replication, poor nutritional status, and adverse
effects of medications.
Rheumatological manifestations
Rheumatological manifestations are
uncommon in HIV-infected children. In one
study, these were identified in 5 (19.2%) of 26
children 26. These included biphasic Raynauds
syndrome, necrotising vasculitis, lip necrosis,
livedo reticularis, knee arthalgia, vasculitis, and
septic arthritis of the ankle. All of the
rheumatologic manifestations were seen in
advanced stages of HIV disease. These
rheumatologic changes were similar to those
reported for HIV-positive adults.
Oral manifestations
Oral manifestations are directly related to
the degree of immunosuppression and such
24
2003;5(4)294
lesions can be considered as indicators of the
progression of the HIV infection in children. In
one study27 involving 80 HIV-infected children
(average age 6.30+ 3.32 years), 30 (38%) had
some type of oral lesions; the CD4 counts were
lower than that found in lesion-free children.
Common lesions included candidiasis (22.5%),
gingivitis (17.5%), enlargement of parotids
(8.8%), herpes simplex (1.3%) and hairy
leukoplakia (1.3%).
Other manifestations 19,21
HIV-infected children also suffer from
various infectious and non-infectious conditions
of the skin. Non infectious conditions include
seborrheic dermatitis, atopic dermatitis, eczema,
drug eruptions and skin lesions associated with
nutritional deficiencies. Up to 10% of HIV-
infected children may have nephropathy. This
may manifest with hematuria, proteinuria, renal
tubular acidosis, and acute renal failure. These
manifestations are more common in children with
advanced disease. Majority of HIV-infected
children suffer from nutritional and growth
abnormalities. Growth retardation in HIV
infected infants is evident as early as 4- 6 months
of age. HIV infection or associated opportunistic
infections first affect linear growth. Overall effect
on height for age is more than weight for age.
Early growth delay has been correlated with high
viral load. In addition, recurrent infections,
decreased oral intake because of oral and
esophageal lesions, and various organ
dysfunctions also contribute to failure to thrive.
Hepatomegaly is a common clinical
manifestation of pediatric HIV disease.
Histopathological findings in liver include: fatty
infiltration of hepatocytes, portal inflammation,
CMV inclusion bodies and giant cell
transformation, and chronic active hepatitis
characterized by lymphocytic infiltration in portal
spaces and lobules. Lymphadenopathy is seen in
infants and children infected with HIV.
 2003;5(4)295

Generalized lymphadenopathy may be because
of HIV infection, other viral infections (Ebstein
Barr virus or CMV), opportunistic and
mycobaterial infections and malignancies
(lymphoma/ leukemia). The prevalence of
malignancies in HIV infected children is believed
to be significantly higher than in the normal
population. The common malignancies reported
in HIV infected children include: non Hodgkins
lymphoma, leiomyosarcoma or leiomyoma,
leukemia, Kaposis sarcoma, Hodgkins
lymphoma, vaginal carcinoma in situ and tracheal
neuroendocrine carcinoma.
Clinical case definition of HIV infection
Since majority of HIV infection are acquired
vertically, the best method for identification of
HIV infection would be to screen all mothers and
suspect HIV in babies born to HIV positive
mothers. Since screening of mothers for HIV is
not done universally and some patients get HIV
infection through transfusion of blood and blood
products, we may see children with clinical
manifestations of HIV in majority.
Because of the limited availability of HIV
diagnostic testing, attempts have been made to
formulate clinical AIDS definitions for adult and
children in developing countries. Use of the
Center for Disease Control and Prevention (CDC)
guidelines for clinical classification of HIV
infection in children is problematic because they
were designed to measure HIV disease
progression, not for the identification of children
infected with HIV. In addition, many category C
(or AIDS) diagnoses are beyond the diagnostic
capabilities of most of the developing world.

Table 5. Clinical Case Definitions of Pediatric AIDS

World Health Organization (WHO) Clinical Case Definition for AIDS in Children
Major signs: Minor signs:
Weight loss or failure to thrive Generalized lymphadenopathy
Chronic diarrhea (>1 mo) Oro-pharyngeal candidiasis
Prolonged fever (> 1 mo) Repeated common infection (otitis, pharyngitis, etc.)
Persistent cough (> 1 mo)
Generalized dermatitis
Confirmed maternal HIV infection
Pediatric AIDS is suspected in an infant or child presenting with at least two major signs associated
with at least two minor signs in the absence of known causes of immunosuppression.
Modified WHO clinical Case Definition for Pediatric AIDS
Major criteria: Minor criteria:
Weight loss or failure to thrive Generalized lymphadenopathy
Chronic diarrhea (>1 mo) Oro-pharyngeal candidiasis
Prolonged fever (> 1 mo) Repeated common infection
Severe or repeated pneumonia
Generalized dermatitis
Confirmed maternal HIV infection
Pediatric AIDS is suspected in an infant or child presenting with at least two major signs associated
with at least two minor signs in the absence of known causes of immunosuppression.

25
Indian Journal of Practical Pediatrics
Several simple clinical case definitions pertinent
to the developing world have been devised and
tested, including the WHO clinical case
definition28 (Table 5). These definitions detect
the presence of symptomatic AIDS and not HIV
infection itself and are confounded by prevalent
conditions such as malnutrition, diarrhoeal
disease and tuberculosis. There are no published
studies in literature to test the sensitivity and
specificity of WHOs modified criteria in Indian
patients. The reported12,13 sensitivity of individual
factors including weight loss or failure to thrive
is 45-100%, Chronic diarrhea (>1 mo) 15-45%,
and severe or repeated pneumonia 8-86%. For
minor criteria such as generalized
lymphadenopathy is 23-41% and for oro-
pharyngeal candidiasis 14-48%. The wide
variation in sensitivity is due to different clinical
settings. The published studies do not mention
about the sensitivity of two major signs associated
with at least two minor signs.
One should suspect HIV infection in a child
who presents with symptoms described in
category C of CDC, has specific illness like LIP,
has atypical manifestations of common illnesses,
presents with combination of symptoms or born
to HIV positive parents.
References
1. WHO/UNAIDS. Epidemiological fact sheet on
HIV/AIDS and sexually transmitted infections.
2002 update. World Health Organization,
Geneva. (accessed from website http://
www.unaids.org/hivaidsinfo/statistics/
fact_sheets/pdfs/India_en.pdf ).
2. Peckham C, Gibb D. Current concepts: Mother-
to-child transmission of the human
immunodeficiency virus. N Engl J Med 1995;
333: 298-302.
3. Lodha R, Singhal T, Jain Y, et al. Pediatric HIV
infection in a tertiary care center in North India:
early impression. Indian Pediatr 2000; 37: 982-
986.
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4. Barnhart HX, Caldwell MB, Thomas P, et al.
Natural history of human immunodeficiency
virus disease in perinatally infected children:
An analysis from the Pediatric Spectrum of
Disease Project. Pediatrics 1996; 97: 710-716.
5. Diaz C, Hanson C, Cooper ER, et al. Disease
progression in a cohort of infants with vertically
acquired HIV infection observed from birth:
The women and infants transmission study. J
Acquir Immune Def Synd Hum Retrovirol
1998; 18: 221-228.
6. Blanche S, Newell ML, Mayaux MJ, et al.
Morbidity and mortality in European children
vertically infected by HIV-1. The French
pediatric HIV infection study group and
European Collaborative Study. J Acquir
Immune Def Synd Hum Retrovirol 1997; 14:
442-450.
7. Spira R, lepage P, Msellati P, et al. Natural
history of human immunodeficiency virus type
1 infection in children: a prospective 5 year
study in Rwanda. Mother to child HIV1
Transmission Study Group. Pediatrics 1999;
104: e56.
8. Lucas SB, Vetter K, Djormand G, et al.
Spectrum of pediatric HIV disease in Abidjan.
Cate d Ivorie (abstract). International
conference on AIDS STD in Africa, December
1995. Abstract ThB 281.
9. Tovo PA, de Martino M, Gabianao C, et al.
Prognostic factors and survival in children with
perinatal HIV-1 infection. Lancet 1992; 339:
1249-1253.
10. Italian Register for HIV infection in children.
Features of children perinatally infected with
HIV-1 surviving longer than 5 years. Lancet
1994; 343: 191-195.
11. Greenberg AE, dabis F, Marum LH, De Cock
KM. HIV infection in Africa In Pizzo P, Wilfert
CM, (Eds.,) Pediatric AIDS: the challenge of
HIV infection in infants, children and
adolescents, 3rd Ed., Williams & Wilkins,
1998, pp 23-48.

12. Merchant RH, Oswal JS, Bhagwat RV, et al.
Clinical profile of HIV infection. Indian Pediatr
2001; 38: 239-246.
13. Dhurat R, Manglani M, Sharma M, et al.
Clinical spectrum of HIV infection. Indian
Pediatr 2000; 37: 831-836.
14. Centre for Disease Control and Prevention.
1994 Revised classification system for human
immunodeficiency virus infection in children
less than 13 years of age. MMWR 1994; 43:
6-8.
15. Krasinski K, Borkowsky W, Bonk et al.
Bacterial infections in humun
immunodeficiency virus infected children.
Pediatr Infect Dis J 1988; 7: 323-328.
16. Mofenson LM, Yogev R, Korelitz J, et al.
Characteristics of acute pneumonia in human
immunodeficiency virus-infected children and
association with long term mortality risk.
Pediatr Infect Dis J 1998; 17: 872-880.
17. Chan SP, Birnbaum J, Rao M, Steiner P.
Clinical manifestations and outcome of
tuberculosis in children with acquired
immunodeficiency syndrome. Pediatr Infect
Dis J 1996; 15: 443-447.
18. Husson RN. Tuberculosis. In: Pizzo PA, Wilfert
CM (Eds). Pediatric AIDS: The challenge of
HIV infection in Infants, children and
adolescents. 3rd edn, Lippincott Williams and
Wilkins, Philadelphia, 1998, pp 139-156.
19. Abrams EJ. Opportunistic infections and other
clinical manifestations of HIV disease in
children.Pediatr Clin N Am 2000; 47: 79-108.
20. Simonds RJ, Orejas G. Pneumocystis carinii
pneumonia and Toxoplasmosis. In: Pizzo PA,
Wilfert CM (Eds). Pediatric AIDS: The
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challenge of HIV infection in Infants, children
and adolescents. 3rd Edn. Lippincott Williams
and Wilkinns, Philadelphia, 1998; 251.
21. Abuzaitoun OR, Hanson IC. Organ-specific
manifestations of HIV disease in children.
Pediatr Clin N Am 2000; 47: 109-125.
22. Pavia AT, Long EG, Ryder RW, et al. Diarrhea
among African Children born to human
immunodeficiency virus1- infected mothers:
Clinical, microbiologic and epidemiologic
features. Pediatr Infect Dis J 1992; 11: 996-
1003.
23. Chintu C, Luo C, Baboo S, et al. Intestinal
parasites in HIV-seropositive Zambian children
with diarrhea. J Trop Pediatr 1995; 41: 149-
152.
24. Mintz M. Neurological and developmental
problems in pediatric HIV infection. J Nutr
1996; 126 (10 Suppl): S 2663-S2673
25. Starc TJ, Lipshultz SE, Easley KA, et al.
Incidence of cardiac abnormalities in children
with human immunodeficiency virus infection:
The prospective P2C2 HIV study. J Pediatr
2002; 141: 327-334.
26. Martinez-Rojano H, Juarez Hernandez E,
Ladron De Guevara G, del Carmen Gorbea-
Robles M.Rheumatologic manifestations of
pediatric HIV infection. AIDS Patient Care
STDS 2001; 15: 519-526.
27. Santos LC, Castro GF, de Souza IP, Oliveira
RH Oral manifestations related to
immunosuppression degree in HIV-positive
children. Braz Dent J 2001; 12: 135-138.
28. World Health Organization. Acquired
immunodeficiency syndrome (AIDS). Wkly
Epidemiologic Rec 1986; 61: 69-73.
Indian Journal of Practical Pediatrics
HIV INFECTION
LABORATORY DIAGNOSIS OF
PEDIATRIC HIV
* Shivananda
** Rajath A
Two distinct human immunodeficiency
viruses, HIV-1 and HIV-2 are the etiologic agents
of AIDS. HIV-1 subtype C is the commonest
variant in India. The prevalence of HIV-2 in India
is believed to be between 6-11%. Initially the HIV
infection alone does not cause significant clinical
manifestations. Thus, laboratory diagnosis is the
only method of determining the status of HIV
infection in an individual during the long
asymptomatic period.
The purpose of this article is to outline
various laboratory tests available to detect HIV
infection.
Kinetics of antibody response in a
HIV infected person
An understanding of the sequence of events
that follow the entry of the virus into the body
will help to understand the optimal usage of
various HIV tests during different stages of HIV
disease.
Viral entry into the body leads to a transient
period of high plasma viremia and p24
antigenemia. Their levels come down within
1-2 months with concomitant immune
response.
* Head of Pediatrics,
Bangalore Medical College and Director,
Indira Gandhi Institute of Child Health,
Bangalore
** Postgraduate in Pediatrics,
Bangalore Medical College, Bangalore.
28
2003;5(4)298
Antibodies against structural envelope
proteins (gag:p15,p17,p24,p55; env:gp41,
gp120, gp160 and pol:p31,p51 and p66),
regulatory proteins (nef, rev, tat) and
accessory proteins (vif and vpu) are
produced. Structural proteins are strongly
immunogenic and almost all tests are based
on the antibody detection against them.
Antibodies against gag proteins (p24 and
p55) are the first to appear and first to
decline. However, antibodies to the env
proteins persist throughout.
IgG response is consistent and better
understood. IgM is valuable in the early
identification of seroconversion. Anti HIV
IgA assay in newborn is diagnostic of
congenital infection as the IgA antibodies
do not cross the placenta. However, IgA and
IgM responses are inconsistent.
The adverse economic, social and
psychological cost of false positive and false
negative assays for HIV infection has pushed the
investigators and manufacturers to develop
diagnostic kits with high sensitivity and
specificity.
Objectives of HIV testing
1] To monitor the trends of HIV infection in a
population or a subgroup for facilitation of
intervention.
2] To test donated blood and prior to organ
donation for ensuring safety of the recipients.
3] To identify individuals with HIV infection
[for diagnosis and for voluntary testing]
4] Research.

HIV testing strategy
Depending upon the objectives different
procedures and strategies are adopted.
Unlinked anonymous testing: This screening is
not directed towards the individual, the blood
collected for other purpose is used for testing. It
is an epidemiological method for measuring the
prevalence of infection.
Voluntary confidential testing: Testing for
diagnosis. Maintaining confidentiality is
important.
Mandatory testing: Such testing is recommended
for screening of donors[semen, organs, tissues].
Strategies of HIV testing in India
Various categories of tests are used in
combinations
1] ELISA/Simple/Rapid/, Elisa/Rapid/Simple
used in strategy I, II
2] Supplemental tests like Western Blot, Line
immunoassay are used in problem cases or
when results are indeterminate.
Strategy I: Serum is subjected to one E/R/S for
HIV. If negative it is to be considered free of
HIV and if positive the sample is taken as
positive. This method is used for ensuring
donation safety.
Strategy II: A serum is considered negative if
the first ELISA is negative. If reactive it is
subjected to a second ELISA which utilizes a
different system from the first one. It is reported
reactive only if the second test confirms the
results of the first. This strategy is used for
surveillance and diagnosis only if some indicator
of the disease is present
Strategy III: It is similar to the above strategy II
with the addition of a third reactive ELISA being
required for a sample to be considered as positive.
29
2003;5(4)299
The test for the first ELISA should have high
sensitivity and for the second and third ELISA
high specificity. It is used to diagnose infection
in asymptomatic individuals.
Testing for HIV infection involves aspects
of pretest counselling, explicit consent and
confidentiality. Laboratory safety must be strictly
followed according to good laboratory practice
(GLP) guidelines and universal precautions must
be observed.
Four types of tests are available:
1. Anti HIV antibody tests
2. Virus based tests
3. Immunological tests
4. Surrogate markers
Specimens used to test for HIV infection
1. Antibody detection: Blood, serum/plasma
2. Antigen detection: Serum/plasma, CSF,
cell culture supernatant
3. Virus isolation and detection of viral nucleic
acids: Plasma, semen, vaginal/cervical
specimens, CSF.
Less successful- Saliva, urine, breast milk,
amniotic fluid and tears.
Anti HIV antibody tests
There are two categories:
I. Screening tests
II. Supplemental tests
I. Screening tests
a. Conventional micro well ELISA tests
b. Rapid tests
Screening tests employed should test
antibodies to both HIV-1 and HIV-2 and their
subtypes including O and N.
Indian Journal of Practical Pediatrics 2003;5(4)300

a. ELISA (Enzyme Linked Immunosorbent These tests also identify and differentiate
Assay) infections by HIV-1 and HIV-2.
This is the most commonly performed test These tests include
to detect HIV antibodies.
Western Blot (WB)
Types of ELISA based on the principle:
Line Immunoassay (LIA)
1. Indirect ELISA
Recombinant Immunoblotting Assay
2. Direct ELISA (RIBA)
3. Competitive ELISA
Western Blot analysis is done by
4. Antigen sandwich electrophoresis of plasma on a pre-impregnated
strip containing various antigens of HIV. WB is
5. Antigen antibody capture assay
interpreted as positive if at least 2 of 3 bands (p24,
Types of ELISA based on antigen utilized: gp41, gp120/160) are positive.
Generation Antigen utilized Direct detection of HIV
First Infected cell lysate Direct detection of virus would be needed
in the following settings
Second Glycoproteins (recombinant)
For diagnosis:
Third Synthetic peptidase
1. HIV infection in the newborn
ELISA can take up to 3 hours to yield results.
2. Indeterminate WB/LIA/RIBA results
b. Rapid Tests:
3. Monitor viral load during antiretroviral
They give results within minutes (3- therapy
30minutes). Various rapid tests available are-
4. HIV infection status during the window
1. Dot blot assays period

2. Particle agglutination (gelatin, RBC, latex, 5. Detection of site specific infection

micro beads) For Research:
3. HIV spot and coombs tests 1. Sub typing of HIV
4. Fluorometric microparticle technologies 2. Cloning genes for diagnostic kits/vaccines

II. Supplemental Tests 3. Generating chimeric viruses

Techniques used:
These tests are used if the results of the
screening tests are discordant and for research 1. Detection of p24 antigen
purposes. Otherwise according to the WHO
2. Culture isolates of HIV
guidelines, an individual reactive to three
different systems of ELISA or rapid tests can be 3. Detection of HIV specific DNA or RNA
labelled to be having HIV infection. Polymerase Chain Reaction (PCR)
30

HIV p24 core antigen
HIV p24 antigen is detected and quantified
using EIA. Sensitivity and specificity reported
are 79% and 99% respectively. It correlates well
with the disease progression. p24 is undetectable
in most asymptomatic patients and infants. It also
shows poor intrasample reproducibility. All these
factors limit the utility of p24 assay.
Immune Complex Dissociated (ICD) p24
antigen
P24 antigen dissociated from the immune
complexes improves the sensitivity of the assay.
However, the sensitivity level is sub optimal for
early diagnosis of HIV infection.
HIV isolation by viral culture
This requires at least P2+ containment
facility and high degree of expertise. Autologous
or heterologous peripheral blood mononuclear
cells (PBMCs) activated with mitogen are co
cultured with infectious material at 37C in 5%
CO2 for about 28 days. The presence of the virus
is detected by presence of p24 antigen or reverse
transcriptase enzyme in the culture supernatant.
This method has the sensitivity and specificity
of PCR, however it is costly, labor intensive and
takes 2 to 4 weeks.
Polymerase Chain Reaction (PCR) for HIV
HIV DNA PCR (Qualitative): This detects
the proviral DNA that is integrated with the host
cell. This is best done using Reverse
Transcriptase (RT) PCR. Because of the high
sensitivity of the test, care is taken to avoid cross
contamination of samples or carry over of
amplified products.
HIV RNA PCR (Quantitative): This is done using
RT PCR or nucleic acid sequence based
amplification (NASBA) and branched chain
DNA (bDNA) techniques. Comparative analyses
31
2003;5(4)301
have shown that quantitative PCR studies are
more sensitive measures of viral load than p24
assays and culture techniques at all stages of HIV
infection, enabling detection of virus in plasma
even when other assays are negative.
Prognostic surrogate markers of HIV/AIDS
in children
These measures help the clinician identify
stage of disease progression and to decide when
to start antiretroviral therapy and also to monitor
the response to treatment.
Four markers can be used:
1. CD4/CD8 lymphocyte count
2. HIV p24 core antigen
3. -2 micro globulin
4. Neopterin
CD4 count is the most important marker.
Based on this, the patients immune status is
classified.CD4 % are more consistent with age
than their absolute values. Abnormal CD4 counts
are always confirmed by a repeat test after one
week. The counts vary with infections and time
of the day, they are higher in the evening.
P24 antigen is useful if used with CD4
counts. -2 globulin (increased levels due to
lymphocyte activation and destruction) and
Neopterin (produced by macrophages activated
by interferon) are not reliable as independent
markers.
Laboratory diagnosis of HIV infection in the
newborn (congenital infection)
The risk of mother to child transmission of
HIV is 25-45%. Maternal IgG to HIV crosses
the placenta and persists for 6-18 months. It is
essential to diagnose infections in newborns as
early as possible. It relieves the parents anxiety
and is helpful to consider antiretroviral therapy
Indian Journal of Practical Pediatrics 2003;5(4)302

in infected babies. PCP prophylaxis can be
stopped if the baby is not infected. Early diagnosis
also helps timely decisions regarding breast
feeding, immunization etc. Distinction between
maternal and neonatal IgG is difficult. The
following tests can be used for early detection of
congenital HIV infection:
1. Detection of IgA and or IgM anti HIV
antibodies: IgA antibodies appear at 3-4
months of age and IgM by six months of
age. IgA after 3 months of age has a
sensitivity of 97.6% and specificity of
99.7%. IgM production is erratic and elicits
false positive results.
2. Estimation of p24 antigen: This has high
frequency of false positivity in the first
month of life.
3. HIV DNA PCR, RNA PCR and Viral
cultures: PCR is preferred over culture
techniques. It invariably has a specificity of
>95%. The sensitivity ranges from 38%
within 48 hours of birth, to more than 93%
at 14 days and 96% by 28 days of life.
Cord blood is not to be used for testing as
there can be contamination. The negative ELISA
done between 6 - 18 months in the absence of
clinical disease will rule out HIV infection[in an
infant who is not breast fed].
For infection in utero , the HIV DNA PCR
or viral culture has to be positive in the first 48
hours.
If one PCR is to be done due to cost
constraints then it is best performed between 3
to 6 months of age.
Reporting procedure
The results are kept confidential.
Negative if the initial/screening test is
nonreactive
Positive- if the sample shows reactive results
by three screening tests.
Indeterminate- If the sample shows
discordant results by three screening tests.
Confirmatory assay is to be done. If the
confirmatory test is indeterminate the follow up
samples are retested at three, six and 12 months
before the result is reported. If still indeterminate
after one year, the person is declared negative.
In summary, to diagnose congenital HIV
infection in early infancy ELISA is unreliable.
The mainstay is by HIV PCR or rarely by viral
culture. After 18 months of age three serial
ELISAs can be done. The disease progress has
to be monitored by assay of CD4 counts.
Test Time Approximate cost
required (rupees)
ELISA upto 3 hours 200
PCR 12 hours 3000
Viral culture 2-4 weeks 6000

For intrapartum infection the tests within CD4 counts 3 - 4 days 800
48 hours are negative but positive after one week.

32

HIV INFECTION
GENERAL MANAGEMENT OF HIV
IN CHILDREN
* Mathur Y C
** Rajiv Chandra Mathur
Abstract: The advent of potent antiretroviral
therapy has enabled transformation of HIV
infection from a fatal to chronic disease in the
developed countries. However supportive care,
appropriate prophylaxis and management of
infections are equally important. In fact, they are
the mainstay of therapy in developing countries
like India where anti retroviral therapy is not
affordable by most patients. This article attempts
to provide an overview of the basic treatment
principles of this increasingly common childhood
illness.
Key words: HIV, Children, Management
Early management of pediatric HIV disease
is based on timely institution of chemoprophyla-
xis, immunization, management of opportunistic
infections, nutritional support and anti retroviral
therapy. However early management using
appropriate measures are possible only if these
children are diagnosed early. Spectacular
advancement has been made in strategies to
reduce mother to child transmission. The vertical
transmission of HIV infection may occur in utero
(30-50%), intrapartum (50-70%), or through
breast feeding (about 15%). Of the HIV infected
children about 20-30% are rapid progressors.
* Senior Consultant Pediatrician
** Consultant Pediatrician & Hepatologist
5 Subhodaya Apartments
Boggulkunta
Hyderabad 500 001
33
2003;5(4)303
Amongst the slow progressors 15% are
asymptomatic even at 5 years of age. The slow
progressors reveal a lower rate of fall of absolute
CD4 counts and generally tend to have higher
CD8 counts. The median survival time of
vertically infected children is reported to be about
8-9 years. Plasma HIV RNA levels of more than
2,99,000 copies per milliliter in an infant has been
correlated with rapid disease progression and
death. In general, plasma HIV RNA load of more
than 1,00,000 copies per milliliter and CD4 of
less than 15% are considered as poor signs of
survival.
Breast feeding
There is a 14-16% risk of mother to child
transmission of HIV through breast milk. In a
developing country like India where the breast
feeding safeguards against risk for diarrhoea and
respiratory infections, which by themselves are
associated with high morbidity and mortality, the
risk from breast feeding needs to be
individualized. Whenever safe, cost effective and
alternative sources of milk are available the HIV
infected women need to be counselled not to
breast feed their infants. Mother and family
participation in the decision making is imperative.
Nutrition
Factors like repeated infections, poor intake,
malabsorption, increased requirements and
emotional deprivation make a HIV positive child
more prone to develop malnutrition. Malnutrition
can itself augment the immuno deficiency of HIV
infected children. The diet should consist of high
calories, proteins and vitamins preferably from
home made foods. Treatment of opportunistic
infections, oro-pharyngeal and esophageal
Indian Journal of Practical Pediatrics
candidiasis, diarrhoea and respiratory infections
is necessary to help in keeping the oral intake
adequate. Health education and economic support
may be necessary for better nutrition. In extreme
or terminal cases tube feeding or total parentral
nutrition may become necessary for a short period
of time. Emotional and psychological support for
the family is required.
Anti retroviral therapy
Three classes of anti retroviral therapies
(ART) are available for HIV. Two of these target,
the reverse transcriptase enzyme, the nucleoside
(NRTI) and non-nucleoside (NNRTI) reverse
transcriptase inhibitors. The third class of drug
is the protease inhibitors, which target the viral
protease enzyme. Drug absorption, metabolism,
pharmacokinetics and interactions should be
understood well before undertaking therapy.
Compliance is also difficult as the drugs are
expensive and some are unpalatable. Treatment
with ART needs proper patient selection,
appropriate choice of drugs, monitoring and
evaluation to look for need for change in
treatment regimens.
Management of opportunistic infections
Prior to use of ART the gains in survival of
HIV infected children were mainly due to
chemoprophylaxis of opportunistic infections.
Pneumocystis carinii pneumonia (PCP) is the
most common infection seen in about a third of
pediatric HIV infected patients and is an
important indicator for AIDS. PCP prophylaxis
is done using Trimethoprim sulphamethoxazole
(TMP-SMX). Fungal infections are common in
HIV/AIDS children. Oral or topical drugs are
used in early cases and intravenous antifungal
agents in non-responders and in wide spread
disease. Cryptococcal meningitis, cytomegalo
virus retinitis, varicella zoster, herpes simplex
virus infection and measles are uncommon in
children.
34
2003;5(4)304
Monitoring of growth and development
Anthropometric measurements at regular
intervals are essential for early recognition of
growth failure and malnutrition. Height, weight,
head circumference and skin fold thickness
measurements can be used to predict disease
progression and overall effectiveness of ART.
Mental development should be monitored as it
can be affected due to encephalopathy and
opportunistic infections.
Counselling
Counseling to the patient and the family
should be an essential ongoing process
throughout the course of the disease. The mother
or care giver should be counselled regarding
diagnosis, treatment, follow up, prophylaxis
against opportunistic infections, immunization,
breast feeding, prevention of transmission of HIV
and socio-economic consequences of the
infection.
Schooling
Children with HIV infection should not be
excluded from school for the protection of other
children or personnel since HIV does not spread
through types of contact that may occur in the
school. The family of an affected child has the
right, but is not obliged to inform the school about
the infection status of the child. All schools
should adopt the standard procedures for handling
blood or contaminated fluids regardless of the
HIV status.
Home care
The family should follow standard
guidelines to prevent exposure to HIV infected
material. Sharing of toothbrushes, razors etc
should be avoided. Hands and body parts should
be washed readily after contact with blood.
Routine changing of diapers and nose wipes
should be followed by hand washing. When blood
or blood-contaminated fluids are spilled the
 2003;5(4)305

surface should be cleaned and then disinfected
with freshly prepared 1: 10 dilution household
bleach.
HIV infected travellers
Some countries prohibit the entry of HIV
infected travellers. They should be vaccinated
early in the disease and prior to travel. Insect
repellents should be used and strict food and
water hygiene should be observed. Isoniazid
prophylaxis may be required for a long-term
traveller to a high endemic zone of tuberculosis.
Immunization
Immunization in the HIV positive children
differs from the routine schedule of vaccination
as live vaccines are contraindicated with some
exceptions. There may be a sub - optimal sero
conversion after vaccination.

Table 1. Recommendations for immunization in a developing country

Vaccine Recommendation
BCG Recommended by WHO, as tuberculosis is rampant
and neonates are asymptomatic.
OPV Ideally IPV should be given. Since it is not available OPV is
recommended, as evidenced by absence of complications in
those who were given OPV in early epidemics.
Measles Measles and MMR vaccines are contraindicated only in
MMR children who are severely immunocompromised. (category C)
DPT These vaccines are recommended because they do not contain
Hepatitis B any live agent. Hepatitis B immunoglobulin should be given
Hemophilus influenza type B within 7 days of exposure.
Varicella Recommended only for the asymptomatic or mildly
symptomatic (CDC classification N1 or A1 with an age specific
CD4 of > 25%). Immunoglobulin should be given within 4 days
of exposure.
Pneumococcal All HIV infected children who are 2 years or older should
receive the vaccine, with a booster 5 years later.
Influenza HIV positive children should receive yearly vaccine after
6 months of age.
Hepatitis A Recommended for those living in endemic areas.
Typhoid Vi polysaccharide vaccine is recommended.
Oral typhoid vaccine is contraindicated.
Rabies Vaccine and immunoglobulin can be given for post exposure
prophylaxis.

35
Indian Journal of Practical Pediatrics
HIV INFECTION
COUNSELLING IN PEDIATRIC
HIV/AIDS
Swati Y. Bhave
Abstract: HIV/AIDS is here to stay. In the fight
against AIDS more than all the drugs and
intervention it will be a test of human resilience,
human support system which will decide how this
battle will be fought. In this respect counselling
is indispensable. In the present scenario of HIV/
AIDS in India, with antiretroviral therapy being
only a dream for most patients, counselling
remains the backbone for management of HIV/
AIDS patients. In order for the individual to
accept the infective status, carry on with life, plan
the future, prevent transmission and continue to
function as a useful member of the community
counselling is a must. Counselling induces a
positive attitude and a high life force in the
individual helping him or her to carry on as
before in spite of and irrespective of the HIV
infection.
Counselling is required when a physician
orders a HIV test i.e. pre test counselling and
when the results are told to the patient i.e. post
test Counselling. This is mandatory as laid down
by WHO/UNAIDS. Government of India is also
actively emphasizing the need for HIV
counselling Preventive counselling is also
required for the community at various levels to
understand and prevent the disease by preventing
transmission of HIV infection. It is done for
* Incharge training program and editor
publications
IAP Project on pediatric and adolescent HIV/
AIDS
36
2003;5(4)306
individuals both with or without risk behaviour.
Supportive counselling facilitates an individual,
family or a group to cope with circumstances
arising as a result of HIV status who need psycho-
social support.
Keywords: Counselling, HIV, AIDS
In the present scenario of HIV/AIDS in
India, with antiretroviral therapy being only a
dream for most patients, counselling remains the
backbone for management of HIV/AIDS patients.
Counselling is required when a physician orders
a HIV test i.e. pre test counselling and when the
results are told to the patient i.e. post test
counselling. Counselling is the mainstay of
management of a patient who has been diagnosed
as HIV positive or who has already gone into
full blown AIDS. The family of the patient
requires extensive counselling to cope up with
the ramifications of the disease. Counselling is
also required for the community at various levels
to understand and prevent the disease i.e.
preventive counselling. Counselling is also
needed for the community to look after the HIV
affected persons in a humane way. Counselling
may be done as one to one, that is individual
counselling or as a group.
Counselling plays a major role in HIV/AIDS
prevention and management. It aims at preventing
transmission of HIV infection. It is done for
individuals both with or without risk behaviour.
Supportive counselling facilitates an individual,
family or a group to cope with circumstances
arising as a result of HIV status who need psycho-
social support .
 2003;5(4)307

Counselling skills Create the confidence of the patient and

assure confidentiality.
Counselling is not about telling a client what
to do nor is it a forum for presentation of the Listen carefully to patients problems.
counselors views. In fact a counselor should
Do not interrupt while patient is talking.
resist making assumptions or jumping to
conclusions. Counselor should avoid comparing Try to elicit more information while patient
one clients problem to other clients similar is talking.
problem Counsel over a number of sessions and be
Skills are required to understand a problem. empathetic.
These are necessary for any doctor or health Provide information over the issue the
professional. Counselling is an art because it patient has come.
has a blend of the skill and personality of the
Help the patient to decide for him or herself.
counselor and a science because of its
underlying principles. In counselling language, Explain how to carry out patients decision.
the patient is referred to as a client. Time to time reassurance and follow up
What to say ? regarding health condition of the patient is
often needed.
Verbal skills are extremely important for
proper rapport building and for explaining to the Interviewing skills
client. listening,
What to do? observing
Non- verbal skills. Acquiring and assurance,
maintaining clients confidence. acceptance
How to be? being patient and trust worthy
receiving information
Body language of the counselor should not
be threatening or disapproving. Counselor must probing
correctly interpret body language of patient. One clarifying doubts
should not show shock or disapproval at any give simple direct answers
comments of the patient. Do not go by the attitude assurance
portrayed. Clinic atmosphere should be
emotional support
friendly.Environment should not be intimidating.
There should be informative reading material anticipatory guidance
lying around. decision making
The key factors are: assurance, empathy
confidentiality, privacy, easy accessibility confidentiality
Elements of counselling reality orientation
motivation
Greet patient skills for solving the problem
Make the patient comfortable understand how the problem has risen

37
Indian Journal of Practical Pediatrics 2003;5(4)308

After initial assessment the counselor has Counsellor makes a mistake

to decide the following
Be honest and courageous to accept the
Direct Treatment mistake

Futher counselling sessions have to be Client asks a personal question

planned
Gently explain that the discussion is about
Referral the client and his or her problems

Appropriate referrals should be planned Client asks counsellor to make a decision

Followup and Homevisit Emphasize that the client has to make

decision himself or herself.
These are extremely important if one desires
good results from counselling Counselling in HIV/AIDS
Why is HIV counselling necessary?
Interviewing skills for adolescents
HIV/AIDS counselling is mandatory for
This requires special skills and different
providing voluntary HIV testing services. This
approach
is because diagnosis of HIV in an otherwise
be open healthy individual induces a series of
psychological reactions like denial, anger,
be flexible
anxiety, depression, to finally acceptance.
be understanding
So far there is no successful cure or vaccine
be approachable available for HIV infection. In order for the
stress confidentiality individual to accept the infective status, carry on
with life, plan the future, prevent transmission
show respect
and continue to function as a useful member of
Meeting counselling challenges the community counselling is a must. Counselling
induces a positive attitude and a high life force
Client is Silent in the individual helping him or her to carry on
Use various methods to coax a repsonse. Do as before, inspite of the HIV infection. HIV/AIDS
not show anger, frustration or intimidation counselling is mandatory (pre and post tests) as
laid down by WHO/UNAIDS. Government of
Client crying India is also actively emphasizing the need for
HIV counselling
Give him or her time to get over her
emotions. Be empathetic without getting The important facts for HIV counselling are
emotionally involved
Infection with HIV is lifelong, so the person
Counsellor does not know answer to the requires lifetime counselling
question
1. A person can avoid acquiring HIV infection
Be frank in saying I do not know and will or transmitting it to others by changing
try to find out. behaviour (primary prevention)
38

2. Motivation for change in high risk behaviour
(secondary prevention)
There is so much fear, misunderstanding and
discrimination provoked by HIV epidemic that
it needs appropriate handling. Suspicion,
recognition or diagnosis of HIV infection or
AIDS can lead to emotional, social, behavioral
and medical consequences leading to immense
psychological pressures.
What is HIV Counselling?
WHO defines HIV/AIDS counselling as a
dialogue between a client and a care provider
aimed at enabling the client to cope with stress
and take personal decisions relating to HIV/
AIDS. The counselling process includes the
evaluation of personal risk of HIV transmission
and the facilitation of preventive behavior
HIV counselling is an on-going dialogue and
relationship between client or patient and
counsellor. The aims are preventing HIV
transmission and providing psychosocial support
for those affected directly and indirectly by HIV.
AIDS/HIV counselling consists of preventive
counselling and supportive counselling
Difference between counselling and health
education
Counselling differs from health education in
many ways
Counselling is usually a one to one process
where as health education addresses a group
of people.
Counselling is useful not only for giving
information but also changing attitudes and
motivating behavioral change. Health
education is used mostly for assessing
information sharing
Counselling sessions involve personal
problem solving. In health education general
issues are discussed
39
2003;5(4)309
Counselling is more focused, specific, and
goal targeted where as health education is
much more generalized.
Counselling evokes strong emotions in both
counsellor and client whereas health
education sessions are generally emotionally
neutral in nature
For whom is HIV/AIDS Counselling Done?
This is very important for those persons who
Are already identified as having AIDS or
being infected with HIV
Those being tested for HIV ( pre and post)
Experience discrimination due to HIV
infection
Family and friends of people with HIV
infection
Those seeking help because of past or current
risk behavior and planning for their future
Those not seeking help but practising high
risk behavior
Health workers/others in regular contact with
HIV infected persons
Where can HIV/AIDS Counselling be
provided?
HIV/AIDS counselling can be provided in
any setup including hospital wards, STD clinics
FP. clinics ,ANC/PNC clinics, blood donation
centers, drug deaddiction centers, primary and
secondary health posts, community based
programs.
Who should provide HIV/AIDS Counselling
HIV AIDS counselling can be provided by
any one who has a sympathetic ear, can give time
to listen, has knowledge of accurate scientific
facts about HIV/AIDS and undergoes systematic
and periodic training in counselling.
Indian Journal of Practical Pediatrics
In addition to doctors, nurses, social
workers, psychologists, psychotherapists, even
teachers, health educationists, community and
peer leaders and youth and self help groups can
undertake preventive and supportive counselling
Main Function of HIV/AIDS Counselling
1 Preventive counselling
Preventing infection with HIV and its
transmission to other people
2 Supportive counselling
Providing psychosocial support
Preventive counselling: Main steps
1 Assessing high risk behaviour in individuals
or group
2 Convincing individual/group to
acknowledge risks associated with such
behaviour
3 Rationalizing the linkage of their life style
and self image to this behaviour
4 Supporting individuals to make rational
decisions for changing behaviour
5 Working with them to sustain the modified
behaviour.
Primary preventive counselling
For people at risk of HIV infection but not
known to be infected - Aware/Unaware. It aims
at creating this change focussing on behaviours
that present a risk for HIV infection and
reviewing ways of managing individual changes.
Secondary preventive counselling
For persons known or considered likely to
be HIV-infected. They should be given specific
instructions as to ways by which they can prevent
spread to others. An attitude of understanding
should be adopted, as the fact that the person is
40
2003;5(4)310
positive is traumatic enough to accept. Since
behavioral change is difficult at least she/ he
should be asked to take precautions: use condom,
while having sexual intercourse, do not share
needles and syringes and do not donate blood.
Supportive Counselling
1 For people with diagnosed HIV infection and
HIV related illness - AIDS Relafed Complex
/ AIDS
2 For relatives/friends close to HIV/AIDS
persons
Counselling for HIV/AIDS is the process of
Empowering the person with HIV/AIDS
Mobilizing the persons own strengths and
resources to face and manage the various
concerns and problems
Essential Features of HIV/AIDS Counselling
Time : A lot of time must be spent to absorb
information/news and to develop rapport
Acceptance and remaining non judgmental
by counsellor irrespective of the life style of
client
Accessibility and availability of counselling
facilities
Consistency and accuracy of any
information
Confidentiality and Trust (Exceptions ?)
Content of pre test counselling
This is aimed at preparing an individual for
HIV test result
It consists of the following
Assessing an individuals risk profile to take
the test
Obtaining information on the personal
history of the client

Sexual behaviour multiple partners,
unprotected sex, homosexuality, bisexuality,
prostitutes; drug users, blood transfusion,
organ transplant.
Assessing the risk of having been exposed
to HIV.
Exploring why the client wants the test.
Understanding what the client already
knows.
What behaviour and symptoms are of
concern to patient
Giving appropriate and relevant information
on HIV/AIDS and on how to prevent
transmission/infection.
Providing accurate information as to the
difference between HIV ( as causative
organism) and AIDS as the terminal stage
of illness.
Explaining the test procedure and waiting
for the result.
Obtaining motivated consent
Anticipatory preparation of the result of the
test and response
Assessing an individuals coping mechanism
and existing support systems specially role
of the family, as a preparation for subsequent
management plans
Content of post test counselling
This should be planned based on the
individuals coping capacity
Helping client to respond to the result.
Assess the level of the individuals
knowledge about HIV/AIDS so that the
counselling is tailor made to suit her /his
needs. The positive results should be given
directly
41
2003;5(4)311
Assisting him/her to understand the meaning
of the result (and what it does not mean).
Appropriate warm pause should be
provided to enable individual to understand
and absorb the meaning of positive test
result.
Considering whom to tell and how to tell.
Imparting relevant medical knowledge
appropriately.
Counsellor should provide adequate time for
an effective dialogue and not be in a hurry
to provide all information in one sitting.
Giving accurate information on how to
prevent HIV transmission.
Considering long term implications
Counsellor should identify major
psychological issues (such as anxiety,
depression) and social issues(discrimination,
interpersonal relationship). This will help to
plan an appropriate intervention for
providing psychological/social and
emotional support.
Some special issues
Pregnancy: Females of childbearing age found
HIV positive should be told to avoid pregnancy,
as there is a risk of vertical transmission from
mother to child
If pregnant: There is one in three chance of
having an infected child. Termination of
pregnancy to be discussed. Counselling will
depend upon personal, religious and cultural is
factors of the patient. Both partners need to be
counselled
Infants: Should be kept under medical
observation and treated with care and affection.
Parents and siblings need to be counseled.
Though the risk of acquiring infection from
Indian Journal of Practical Pediatrics 2003;5(4)312

infants body fluid is minimal, nevertheless Issues after positive results

people with cuts should avoid contact with fluids.
Hygienic precautions should be emphasized First discussion - private and confidential
upon. Time given for patient to adjust to the news
Breast feeding: May result in transmission of and understand all implications of being HIV
HIV from mother to child. In our country positive. i.e. meaning and social/medical
stoppage of breast-feeding may deprive the implication of the result.
newborn of protective immunity from mother. No speculation of prognosis of estimate of
Counselling will require a balance between the time left to live but providing support
two. The possibility of acquiring HIV infection
and lack of immunity and other benefits of human Information of how to prevent further
milk if not breast-fed. One should impart all transmission
scientific knowledge to the mother and she should
Information where resources are available
take the final decision
and possible treatment of some of the
Counselling after a negative result symptoms of HIV infection and efficacy of
anti-retroviral treatment.
Usual response is relief or euphoria. However
the patient has to be cautioned that there is a Psychosocial support
window period for 3 months, during which a
Besides the individual who has been tested
negative result cannot be considered reliable. A
and found to be positive, counselling is also
negative test carries greater certainty if six months
needed for others around him i.e. the health
have passed from the last exposure. A negative
workers and family to face and share of fears
test should not give a false sense of security. In
and uncertainties regarding their getting the
general, patient should be advised safer sex
infection. All have to be given full and proper
practices. Prevent further exposure by avoiding
information so that they can provide support,
high risk behavior, avoidance of needle sharing.
which the individual requires to be able to
Provide other information on avoidance of HIV
face his/her problems.
infection.
Counselling after an equivocal test result
Counselling after a positive result
(10% samples in some areas)
Usual response is a mixture of negative
emotions Meaning of the result
Fears are related to illness, death, job, length Test is cross-reacting with a non-HIV protein
of life etc
Insufficient time for full seroconversion -
Loss due to stigma attached by society and since HIV exposure
speculation in the minds of people regarding
the behavior of those affected by HIV Options

Anxiety regarding all aspects of life guilt , Use other methods to get a reliable result
grief, denial, anger, depression, suicidal Stop further testing for the moment - advise
activity repeat test after three months

42
 2003;5(4)313

Issues
Information on prevention of transmission
Support while waiting for an unequivocal
result
HIV/AIDS is here to stay. It is slowly but
surely spreading its tentacles and pervading all
sections of society. No one can remain isolated
from this menace. Each individual in todays
society will be called upon to play some role
sooner or later. In the fight against AIDS more
than all the drugs and intervention it will be a
test of human resilience, human support system
which will decide how this battle will be fought.
In this respect counselling is indispensable.
Bibliography
1. Counselling in HIV infection. In: NACO
training module on HIV infection and AIDS
for medical officers. Ministry of health and
family welfare, 2000 Unit XI, pp 80-25
2. Counselling and HIV/AIDS testing. NACO
training module on HIV infection and AIDS
for medical officers, Ministry of health and
family welfare, 2000, pp 143-45
3. Counselling NACO training module on HIV
infection and AIDS for medical officers,
Ministry of health and family welfare, pp 91-
93
4. HIV infection in women and children. Eds
Rashid Merchant & Kaizad Damania. Ist ed
1995, AL Printers, Mumbai Educational grant
by CIPLA, pp 162-164

NEWS AND NOTES

SNIDS AND NIDS FOR POLIO 2003-2004

Government of India has organized Subnational Immunization days (SNIDs) on 14Th September
2003 and 9th November 2003 and National immunization days (NIDs) on 4th January 2004 and
22nd February 2004 for polio immunization. SNIDs will be conducted all over the state in the states
of Uttar Pradesh, Bihar, Delhi, Gujarat, Haryana, Rajasthan, Jharkhand and West Bengal and in
31 districts of MP and 4 districts of Uttaranchal. NIDs will be conducted all over India. All IAP
members are requested to keep their clinics open and advice parents to bring their children on these
dates for polio immunization.
T. Jacob John Naveen Thacker
Chairperson Convener
Polio Eradication Committee, IAP

A.P.PEDICON 2003
HOSTED BY IAP NELLORE DIST. BRANCH
Date: November 15th & 16th 2003
Venue: Nellore, A.P.
Address for correspondence:
Dr.Z.Sivaprasad
Siddartha Hospital, 16/II/306, Near Vijayamahal Gate, Nellore 524 001. A.P.
Ph:0861-2320808 , 2306426 , Mobile: 98495 46456.

43
Indian Journal of Practical Pediatrics
HIV INFECTION
OPPORTUNISTIC INFECTIONS
IN PEDIATRIC HIV DISEASE
* Rinku Agarwal
** Milind S Tullu
*** Sandeep B. Bavdekar
Abstract: Opportunistic infections (OI) are the
hallmark of the immunodeficiency associated
with HIV infection in children. As HIV infection
affects the cellular as well as the humoral arms
of the immune system all types of organisms,
viruses, bacteria, fungi, protozoa and
mycobacteria, are responsible for OI. The pattern
of OI in children differs from that in adults. The
type of OI encountered in children is dependent
upon the patients age as well as on the degree
of immunosuppression. Opportunistic infections
should be managed with vigor. Efforts should be
made to identify the causative organism, so that
early treatment can be instituted. Prophylactic
regimens, both primary and secondary, are
available for most OI. They have decreased the
morbidity and mortality associated with HIV
infection and have improved the quality of life of
HIV infected children. Prophylaxis does not mean
prescribing medications alone. The pediatrician
has a much wider role in prevention of OI that
includes giving counseling regarding hygienic
practices, offering appropriate vaccinations and
giving advice regarding maintenance of nutrition
and avoiding infections. Effective anti-retroviral
* Senior Registrar
** Lecturer
*** Professor
Department of Pediatrics,
Seth G. S. Medical College and
KEM Hospital, Parel, Mumbai 400 012,
Maharashtra, India
44
2003;5(4)314
therapy (ART) helps arrest to immune function
deterioration and may even lead to improvement
in immune function; thereby decreasing the
incidence and severity of OI. The diagnosis,
prophylaxis and treatment of OI are an integral
component of comprehensive HIV care. Given
the wide spectrum of health services available in
the developing countries, including India, there
is a need to evolve standard protocols for
management of OI taking into consideration the
facilities available at different grades of
healthcare system.
Keywords: Opportunistic Infection, HIV,
Children, Prophylaxis
HIV infection primarily affects the immune
system. Hence, opportunistic infections (OI) are
commonly encountered in individuals infected
with HIV1. It is important for the pediatricians to
know about OI for the following
a. Frequently, OI may be the first manifestation
of pediatric HIV infection. pneumocystis
carinii pneumonia (PCP) or persistent oral
thrush can be the first manifestation of the
disease in infancy. The treating physician
should be aware of this fact and thus
investigate such a child for HIV infection.
b. Many a times these infections present with
unusual and/or severe manifestations. For
example, cytomegalovirus (CMV) does not
give rise to severe manifestations in the post-
neonatal age group. However, when
associated with HIV infection, it can present
with features such as retinitis, colitis and
hepatitis.
c. Even infection with the usual pathogenic
organisms can present with unusual or severe

clinical features. For example, chickenpox
is an inconsequential illness in most young
children. However, in HIV infected children
it has a higher probability of presenting with
severe life-threatening manifestations
(progressive varicella syndrome) such as
pneumonitis, hepatitis and encephalopathy.
Similarly, Candida albicans commonly
causes oral thrush that responds well to
conventional measures. However, in HIV
infected children, oral thrush can cause
esophagitis and the infection could be
resistant to the commonly used anti-fungal
agents.
d. The pediatrician should be well versed with
the clinical features and diagnostic studies
of these infections so that early treatment can
be instituted. This improves the prognosis.
For example, if the treatment of PCP is
commenced early, the prognosis is much
better than if the diagnosis itself is delayed.
e. Prophylactic regimens can be used to prevent
a number of opportunistic infections. This
has improved the prognosis for HIV-infected
children. If the primary diagnosis is
established, secondary prophylactic
regimens can be started. This holds true,
among others, for PCP, disseminated
Mycobacterium avium complex (MAC)
infections and toxoplasmosis.
Infectious agents take the opportunity of
defective immune system to cause opportunistic
infections. The type of opportunistic infection
encountered depends on the type of immune
defect. For example, fungal infections are
common in diseases with defective cellular
immunity while bacterial infections are common
in diseases affecting humoral immunity (e.g.
hypogammaglobulinemia). The primary immune
defect in HIV infection is related to destruction
of CD4 cells. Hence, it is not surprising that
opportunistic fungal, viral and parasitic infections
45
2003;5(4)315
are seen with HIV infection. However, CD4 cells
and T-helper cells are also required for proper
functioning of humoral immunity. Hence, HIV
infection is also associated with recurrent and
severe bacterial infections2. Iatrogenic factors like
the use of immunosuppressive anti-retroviral
drugs and insertion of catheters that breach
natural barriers like skin, further accentuate the
immune defect caused by HIV. The probability
of an organism causing an infection is dependent
upon its virulence and is inversely proportional
to the host resistance. When the immune function
is normal, only the organisms with high virulence
are able to cause infection. When immune
function is deficient, as in patients with HIV
infection, organisms with low virulence (which
are abundant in environment) are also able to
establish an infection and cause disease. In fact,
as these organisms with low virulence far
outnumber those with high virulence, infections
with less virulent organisms are commonly
encountered in HIV infected children.
Profile of Opportunistic Infections
Although any and all organisms can cause
infection in these children, certain infections are
commonly encountered. Table 1 shows the
opportunistic infections that have been reported
in various Indian studies. The type of infection
is related to the patients age as well as to the
degree of immunosuppression. For example, HIV
infected infants are prone to develop symptomatic
Pneumocystis carinii pneumonia (PCP).
Persistent and recurrent oral thrush that does not
respond easily to anti-fungal treatment is seen
with minimal immunosuppression and MAC
infections are encountered with severe
immunosuppression. There are infections that
occur without any relation to degree of
immunosuppresion. The classical example of
such a relationship is tuberculosis.
The Center for Disease Control (CDC) has
given a revised clinical classification for
Indian Journal of Practical Pediatrics 2003;5(4)316

Table 1. Incidence of opportunistic infections in children infected with HIV

AUTHOR DETAILS ON OPPORTUNISTIC INFECTIONS
3
Merchant et al 24% of children admitted for chronic diarrhea were seropositive.
4
Daga et al Recurrent diarrhea was the most frequent manifestation of HIV infection
in children and was present in 42.7% in ELISA positive symptomatic
patients.
5
Dhurat et al In 55 HIV infected children, tuberculosis (67.5%), oral candidiasis (23.6%)
and chronic diarrhea (18.2%) were the commonest manifestations
encountered.
6
Karande et al Oral candidiasis was a significant independent risk factor for predicting
HIV infection.

designating children with symptomatic HIV
infection7. Children with opportunistic infections
like persistent oropharyngeal candidiasis, CMV
infection (with onset at age less than one month),
Herpes simplex virus (HSV) infection and
disseminated varicella are included in category
B. Those with recurrent bacterial infections,
esophageal candidiasis, CMV after 1 month of
age, tuberculosis, atypical mycobacterium
infections, PCP and chronic diarrhea are grouped
in Category C.
There are certain differences between OI
occurring in adults and those occurring in
children. In adults, OI usually represent
reactivation of a latent infection acquired early
in life. In contrast, young children generally have
primary infections with these organisms and since
they lack prior immunity, often have a more
fulminant course. Certain infections such as PCP
and recurrent bacterial infections, which are
features of pediatric HIV disease, are rarely
encountered in adults with HIV infection.

Table 2. Relationship between opportunistic infections and CD4 counts in

older children
Stage of HIV CD4 cell count Prevalent Opportunistic Infections
Infection (Cells per mm )
3

Initial infection Much above 500 OI rarely reported

Early HIV disease Just over 500 Pulmonary tuberculosis, MAC, histoplasmosis, Herpes
simplex labialis
Intermediate stage 200-500 Recurrent bacterial infections, Pulmonary tuberculosis
Late stage 50-200 PCP, Toxoplasma gondii, Esophageal candidiasis,
Pulmonary tuberculosis
Advanced stage <50 cells MAC, Cryptococcal meningitis, CMV retinitis,
Pulmonary tuberculosis
MAC: Mycobacterium avium complex; PCP: Pneumocystis carinii pneumonia
*Modified from Reference 8
46

Increased viral load and low CD4 count have
been shown to predict the development of
opportunistic infections in children8. Table 2
shows the correlation of the CD4 counts and the
occurrence of specific opportunistic infections.
Clinical manifestations of opportunistic
infections
It will not be possible to describe clinical
manifestations and diagnostic investigations of
all OIs encountered in HIV-infected children.
This information is available in standard texts1,2.
Table 3 shows the clinical manifestations and
diagnostic features of certain important OIs.
Tuberculosis and HIV
Tuberculosis is a common HIV-related OI10.
HIV infection increases the susceptibility to
primary infection, as well as to reactivation of
tuberculous infection due to depressed cellme-
diated immunity2,9. Children with low CD4 counts
may be at higher risk for development of
tuberculosis, but as stated earlier, children at all
stages of HIV infection can develop the
infection 2,9. Some authorities are of the opinion
that HIV is associated with a high incidence of
drug resistance as well 2,10. The progressive
depletion and dysfunction of CD4 cells and
defective functioning of macrophages and
monocytes in HIV infected children are
responsible for the development of extensive
tuberculosis.
Co-infection of HIV and tuberculosis
impacts both the disease processes. In the
presence of HIV infection, extra-pulmonary and
disseminated forms are more common2,9,10 and
HIV infection can induce latent infection to
progress to a clinically active disease9. In turn,
active tuberculosis accelerates the progression of
HIV disease. Tuberculosis causes activation of
cytokines especially tumor necrosis factor (TNF).
Increased elaboration of cytokines and increased
stimulation and enhanced multiplication of
47
2003;5(4)317
lymphocytes increases HIV replication and
plasma HIVRNA levels8.
The co-infection of HIV and tuberculosis
poses diagnostic problems for the clinician. HIV
infected children may develop extra-pulmonary
disease and atypical symptoms. Pediatricians give
considerable importance to results of Mantoux
test while diagnosing tuberculosis. The test is not
perfect at best of times. The interpretation
becomes much more problematic in the presence
of HIV infection as even with tuberculous
infection and disease, the test is likely to show a
falsely negative result. Hence, it is advocated that
an induration of 5mm or more, be taken as
indicative of a positive test. The treatment of
tuberculosis in HIV infected individuals does not
differ greatly from that in immunocompetent
hosts. Children with pulmonary disease should
be treated for 6-12 months, whereas extra-
pulmonary disease requires 12 months of
treatment2. Rifampicin is a potent inducer of
cytochrome P-450 enzyme system. It, therefore,
enhances the metabolism of protease inhibitors
or non-nucleotide reverse transcriptase inhibitors
used in the treatment of HIV infection. In adults
receiving these drugs, some clinicians substitute
rifabutin for rifampicin. However, paucity of data
precludes offering any definite guidelines
regarding treating children on similar grounds2,9.
It is vital to trace the adult contact responsible
for transmitting tuberculosis. If the adult has been
incompletely or inadequately treated or is infected
with multi-drug resistant (MDR) infection, the
child would have to be treated as a case of MDR-
TB.
Management of opportunistic infections
Opportunistic infections should be managed
with vigor. Affordable treatment is available for
many OI, which are described in standard
reviews 2,11. Indias National AIDS Control
(NACO) Program offers free treatment and
Indian Journal of Practical Pediatrics 2003;5(4)318

Table 3. Common opportunistic infections: Clinical manifestations and

diagnostic modalities2,8,9
Infectious agent Clinical manifestations Diagnostic tests
Pneumocystis Pneumonia is the commonest Demonstration of trophozoite
carinii presenting feature. Manifests with on specimen obtained by BAL or
fever, cough, breathlessness, cyanosis, in sputum or tracheal secretion; lung
tachypnea, fine rales biopsy
M. tuberculosis Organ-specific manifestations Demonstration of organism, specific
histopathological features and
supportive evidence in the form of
contact tracing, chest radiograph
and Mantoux test
Atypical
mycobacteria Pulmonary and disseminated disease Isolation of organism by blood
culture, typical histopathological
features on biopsy of lymph node,
bone marrow or other tissues
HSV Orolabial ulcers, genital ulcers and Isolation of virus in culture.
HSV encephalitis Detection of HSV 1 or 2 antigens
from skin or mucosal scrapings by
immunofluorescent technique
HSV DNA in CSF depending upon
the site of infection
VZV Severe infection, recurrent, persistent Clinical picture is classical.
and chronic infections VZV specific IgM and PCR can
help confirm infection
CMV Retinitis Fundoscopy: Yellowish white area
of retinal necrosis with peri-vascular
exudates and hemorrhage at the
periphery.
GI Involvement, colitis Mucosal biopsy and demonstration
of CMV inclusion bodies
Esophagitis Endoscopy: small confluent ulcers
Cryptococcus
neoformans Subacute or chronic meningoencephalitis CSF: Cryptococcal antigen
detection and culture
Candidiasis Oral Pseudohyphae on KOH stained
specimens
Esophageal Endoscopy and biopsy
Toxoplasma Congenital: low birth weight,
microcephaly hydrocephalus, IgM, IgA antibodies in serum
chorioretinitis
contd.
48
 2003;5(4)319

Presence of IgG antibody in CSF

and intra-cranial granulomas and
calcification on CT scan
Recurrent Two or more bacteriologically Relevant investigations to be carried
bacterial documented systemic bacterial out depending upon the site of
infections infections in 2-year period in the infection. All efforts should be
form of bacteremia, pneumonia, made to isolate the causative
meningitis, osteomyelitis, sinusitis and organism
skin, ear and upper respiratory infections
Chronic Passage of 3 or more loose stools for Microscopic examination of the
diarrhoea* more than 14 days stool sample (special stains),
Immunological tests: IF, antibody,
LA, Serology: ELISA for IgG, IgM,
IgA levels.
CMV: cytomegalovirus, LA: latex agglutination, IF: immunofluorescence, CNS: Central Nervous system, HSV: Herpes
simplex virus, VZV: Varicella zoster virus, BAL: Broncho-alveolar lavage
* Caused by- Protozoa: Isospora belli, Cryptosporidium parvum, Microsporidia, Entemoeba histolytica, Giardia lamblia;
Bacteria: Salmonella, campylobacter, shigella, Clostridium difficle and MAC; Viruses: CMV, adenovirus, HIV, HSV and
rotavirus; Fungi: Histoplasma

prophylaxis for opportunistic infections. Early development of OI. The incidence,

institution of treatment gives gratifying results
in terms of decreased mortality and morbidity.
Certain principles in management of OI are
worthy of consideration2:
a. It is important to develop a broad and
inclusive differential diagnosis while
approaching a case of OI.
b. Maximum possible efforts should be made
to obtain tissue and or body fluid specimens
to establish a definitive diagnosis. Many
infective episodes have to be followed by
secondary prophylaxis. This will not be
possible unless the etiology of infection has
been determined.
c. Complications of drug therapy, especially
adverse drug reactions should be considered
while treating children with HIV infection.
d. Multiple studies have demonstrated a direct
relationship between high viral load, low
CD4 count and the risk for progression and
49
frequency and severity of OI are decreased
as immune function improves. This is
possible only with institution of effective
anti-retroviral therapy (ART). Therefore, the
possibility of institution of ART should
always be explored.
Prophylaxis
Opportunistic infections are responsible for
a considerable proportion of mortality and
morbidity in pediatric HIV infection.
Prophylactic regimens can be used to prevent a
number of opportunistic infections1,11. Table IV
and V show prophylactic regimens for prevention
of OI. In general, prophylactic regimens are
divided as primary and secondary. Primary
prophylaxis is advised on the basis of depression
of CD4 counts and other factors even before the
child has suffered from an episode of the OI.
Prophylaxis to prevent PCP in infants is an
example for primary prophylaxis being offered
irrespective of CD4 count. In contrast, primary
Indian Journal of Practical Pediatrics
prophylaxis against Mycobacterium avium
complex (MAC) is offered on the basis of
depression in CD4 counts. Secondary
prophylaxis is instituted for many infections after
one or more episodes of an infection. Once begun,
the prophylaxis has to be given life-long unless
the immune function improves in response to
effective ART. More clinical studies are required
to address the specific questions regarding timing
of withdrawal of the prophylaxis1. The guidelines
issued by the US Public Health Service (USPHS)
and Infectious Diseases Society of America
(IDSA) for primary and secondary prophylaxis
are summarized in Tables 4 and Table 5. Table 6
outlines the treatment of common opportunistic
infections in HIV.
Although prophylactic regimens are
effective in preventing several episodes of OI,
they are not always effective. Most patients need
to continue them life-long. Probability of drug
interactions, possibility of adverse events,
complex drug regimens and high cost are its other
limitations 2. It is, therefore, important to
emphasize that offering effective anti-retroviral
therapy is the best way to prevent OI2,9. The future
epidemiology of OI is linked inextricably with
the effectiveness of future antiretroviral
treatments. Nonetheless, the prophylaxis,
diagnosis and treatment of OIs are likely to
remain integral component of HIV care2.
Important issues in management of OI
It is alright to say that one should diagnose
the causative agent of all OIs. However, this may
not always be possible. Even in the tertiary care
centers where all investigative modalities are
available, physicians may be reluctant to do
invasive procedures for diagnosis. If this
reluctance stems out of fear of acquiring HIV
infection, they need to be informed about the
ways of protecting themselves. At times, the
reluctance may originate from concerns about the
50
2003;5(4)320
ability of the ill child to tolerate the procedure.
The situation is vastly different when a
pediatrician or a doctor has to manage a case of
OI in a primary health care setting, where hardly
any investigations are available. It is necessary
that professional bodies develop guidelines
regarding management of OI in these situations.
The guidelines could be based on syndromic
approach, wherein the clinician is able to make
a diagnosis on the basis of clinical manifestations
and minimal number of investigations. The
purpose of such an exercise would be to enable
the primary care physicians to offer appropriate
care to HIV infected children with the resources
at their disposal. The guidelines should be based
on situation on the ground and should clearly
delineate the indications for referral to a higher
level of care.
Role of a pediatrician
The treating pediatricians should be aware
of the fact that OI may be the first manifestation
of pediatric HIV infection. They should
investigate for HIV infection if the patient
presents with unusual and severe manifestations
of OI. HIV infection should be suspected in
patients with:
1. Unexplained cyanosis, which may point
towards diagnosis of PCP,
2. Chronic diarrhea along with failure to thrive,
persistent fever, oral thrush,
3. Persistent and/or extensive oral thrush,
4. Persistent fever, not responding to anti-
malarial drugs or antibiotic therapy,
5. Unexplained encephalopathy,
6. Severe, extra-pulmonary, multi-drug
resistant (MDR) tuberculosis,
7. Recurrent bacterial infections
 2003;5(4)321

Table 4. Primary prophylaxis for opportunistic infections in HIV-infected infants and

children11
Pathogen Indication Agents used for primary prophylaxis
Pneumocystis HIV-infected or HIV- TMP-SMZ, Dapsone, aerosolized
carinii indeterminate, infants aged 1-12 pentamidine or Atovaquone
mo, HIV-infected children with
CD4 count < 15%
MTB (isoniazid- MT 5mm or contact with any case Isoniazid or Rifampicin
sensitive) of active tuberculosis
MTB (Isoniazid- Same as above; high probability of Rifampicin
resistant) exposure to isoniazid-resistant
tuberculosis
MTB (Multidrug- Same as above; high probability of The agent to be used as per the sensitivity
isoniazid and rifam exposure to multi-drug resistant of the organism
picin resistant) tuberculosis
MAC For children aged 6 yr: CD4+count Clarithromycin, Azithromycin or
<50/L; rifabutin
Age 2-6 yr: CD4+count <75/L;
Age 1-2 yr: CD4+count <500/L;
Age < 1yr: CD4+count < 750/L
VZV Significant exposure to varicella or VZIG within 96 hr
shingles with no previous history of
chickenpox or shingles
Vaccine preven- HIV exposure / infection Routine immunizations
table pathogens
Toxoplasma IgG antibody to Toxoplasma and TMP-SMZ or dapsone plus pyrime-
gondii severe immunosuppression thamine plus leucovorin or atovaquone
Influenza virus All patients (annually, before Inactivated split trivalent influenza
influenza season) vaccine, Oseltamivir, Rimantadine or
amantadine
Invasive Hypogamma-globulinemia (i.e. IgG IVIG
bacterial < 400 mg/dL)
infections
Cryptococcus Severe immunosuppression Fluconazole or Itraconazole
neoformans
Histoplasma Severe immunosuppression,
capsulatum endemic geographic area Itraconazole
Cytomegalovirus CMV antibody positivity and
(CMV) severe immunsuppression ganciclovir
Abbreviations: MTB: Mycobacterium tuberculosis, MAC: Mycobacterium avium complex, MT: Mantoux test; TMP-
SMZ: trimethoprim-sulfamethoxazole

51
Indian Journal of Practical Pediatrics 2003;5(4)322

Table 5. Secondary prophylaxis to prevent recurrence of opportunistic

infections in HIV-infected infants and children11
Pathogen
Pneumocystis carinii
Toxoplasma gondii
Mycobacterium avium
complex
Cryptococcus neoformans
Histoplasma capsulatum
Coccidioides immitis
Cytomegalovirus
Salmonella species
(non-typhi)3
Invasive bacterial infections
Herpes simplex virus
[Frequent /severe recurrences]
Oropharyngeal Candida
[Frequent/severe recurrences]
Esophageal Candidiasis
[Frequent/severe recurrences]
Abbreviations: IVIG = intravenous immune globulin; TMPSMZ = trimethoprim sulfamethoxazole.
Agents Used for Secondary Prophylaxis
TMP SMZ, dapsone, aerosolized pentamidine or atovaquone
Sulfadiazine plus pyrimethamine plus leucovorin or
clindamycin plus pyrimethamine plus leucovorin
Clarithromycin plus ethambutol with or without rifabutin or
azithromycin plus ethambutol with or without rifabutin
Fluconazole, amphotericin B or itraconazole
Itraconazole or amphotericin B
Fluconazole, amphotericin B or itraconazole
Ganciclovir or foscarnet
TMP-SMZ
TMP-SMZ or IVIG
Acyclovir
Fluconazole
Fluconazole, intraconazole

No efforts should be spared to establish the possibility of institution of effective ART.

etiology of the OI. This is vital as it is difficult to
institute secondary prophylaxis without the
correct primary diagnosis. Having said this, it is
also important that in certain OI, treatment should
not be withheld just for the sake of lack of
conclusive evidence. For example, treatment of
PCP is an emergency. The prognosis is worse if
treatment is delayed by 48 hours. Hence,
treatment should be started and simultaneously
efforts be made to determine the causative agent.
High viral load and low CD4 counts are
associated with increased frequency of OI.
Hence, the pediatrician should explore the
52
The role of pediatricians in prevention of
OI does not end with prescribing medications.
All efforts should be made to emphasize the
importance of maintenance of nutrition, balanced
diet and good personal hygiene. They should
advise the parents that the child should receive
freshly cooked food, should not swim in river
water and should avoid contact with infected
individuals to the extent possible. They should
also give advice regarding appropriate
immunizations for prevention of vaccine-
preventable diseases.
 2003;5(4)323

Table 6. Treatment of common opportunistic infections2,3

Condition Standard treatment Alternative Treatment
Drug Dosage Drug Dosage
PCP TMP-SMZ 20mg/kg/d of Pentamidine 4mg/kg/day iv as a
TMP po or iv single dose for 21 days
in 4 div doses
for 21 d
Steroids For 7-10 d

Recurrent Broad-spectrum antibiotics till isolation of organism. This may be followed by

bacterial specific antimicrobial agent depending upon response to therapy and antimi
infections crobial sensitivity report
MAC Complex Clarithromycin or 15mg/kg in 2 divided doses
Azithromycin with Ethambutol 10mg/kg once daily
and/orRifabutin 15-20 mg/kg/d
5-10 mg/kg/d
MTB Isoniazid Rifampicin 10-20 mg/kg/d, max.300 mg/d
Pyrazinamide Ethambutol or 10-20 mg/kg/d, Max. 600mg/d
Streptomycin 30 mg/kg/d
15 mg/kg/d
20-30 mg/kg/d
Candidiasis Topical nystatin 100,000 - Oral 3-6 mg/kg/d Once
Oral 500,000 U fluconazole daily for 14 days
4 times a day

Oesophageal Fluconazole 3-6 mg/kg d po Amphotericin 0.5-1 mg/kg/d for

/iv for 21 days 14-21 days
Cryptococcosis Amphotericin 0.5-1 mg/kg/d Fluconazole 400-800 mg/d
for 14-21 days
Toxoplasmosis Sulphadiazone, 85-120 mg/kg/d
in 2-4 divided
doses
Pyrimethamine, 1mg/kg/d, single
dose
Folinic acid 5-10 mg every
3 days
CMV Gancyclovir 10mg/kg/d in 2 Foscarnet 180 mg/kg/d in 3
divided doses divided doses IV
for 14-21 days for 14-21 days
Varicella zoster Acyclovir 1500 mg/m2/d iv Foscarnet 180 mg/kg/d in 3

contd.
53
Indian Journal of Practical Pediatrics 2003;5(4)324

If CD4 count in 3 divided divided doses IV

is low: doses for 10 days. for 14-21 days
Mild infection Acyclovir, oral 80mg/kg/d in
and relatively 4 divided doses
good immune
system
Herpes Simplex
Virus Acyclovir 80mg/kg/d in Foscarnet 180 mg/kg/d in 3
3 4 divided divided doses IV
doses for 10 days for 14-21 days
Note: TMP-SMZ: Trimethoprim-Sulfamethoxazole; MTB: Mycobacterium tuberculosis; CMV:
Cytomegalovirus

Acknowledgement infection in hospitalized children in Bombay,

The authors thank Dr. N.A. Kshirsagar-
Dean, Seth G.S. Medical College & KEM
Hospital, Parel, Mumbai 400012 for granting
permission to publish the manuscript.
References
1. Tantisiriwat W, Powderly WG. Prophylaxis
of opportunistic infect. Infecti Dis Clin North
Am 2000, 14: 929 944.
2. Abrams EJ. Opportunistic infections and other
clinical manifestations of HIV disease in
children. Pediatri Clin North Am 2000; 47: 79-
108.
3. Merchant RH, Shroff RC. HIV seroprevalence
in disseminated tuberculosis and chronic
diarrhoea. Indian Pediatr 1998; 35: 883-887.
10. HIV and TB: A guide for counsellors. New
4. Daga SR, Verma B, Gosavi DV. HIV infection
in children: Indian experience. Indian Pediatr
1999; 36: 1250-1253.
5. Dhurat R, Manglani M, Sharma R, Shah NK.
11. 2001 USPHS/ IDSA guidelines for the
Clinical spectrum of HIV infection. Indian
Pediatr 2000; 37: 831-836.
6. Karande S, Bhalke S, Kelkar A, Ahuja S,
Kulkarni M, Mathur M. Utility of clinically-
directed selective screening to diagnose HIV
India. Journal Trop Pediatr 2002; 48: 149-155.
7. Centers for Disease Control and Prevention.
Revised classification system for human
immunodeficiency virus infection in children
less than 13 years of age. MMWR Morb Mortal
Wkly Rep 1994; 43: 1-10.
8. Baveja UK, Sokhey J. Manual on Laboratory
Diagnosis Of Common Opportunistic
Infections Associated with HIV/AIDS, New
Delhi, National Institute of Communicable
Diseases and National AIDS Control
Organisation
9. Mumbai Districts AIDS control society.
Training Manual for Doctors, New Delhi,
National AIDS Control Organisation.
Delhi, Ministry of Health and Family Welfare,
National AIDS Control Organization and
Government of India.
prevention of opportunistic infections in
persons infected with human
immunodeficiency virus. USPHS / IDSA
prevention of opportunistic infections working
group. http://www.aidsinfo.nih.gov/guidelines.

54

HIV INFECTION
ANTIRETROVIRAL THERAPY
(ART)
* Archana Kher
Abstract: Effective antiretroviral therapy [ART]
has improved the mortality and morbidity due to
HIV infection in the developed nations. Potent
regimens require a combination of three or more
drugs to suppress the viral replication to very
low levels. Before commencing therapy, various
issues such as guidelines for initiation of
treatment, monitoring, toxicity, resistance,
compliance and adherence to treatment need to
be adequately addressed. Cost and access to
health care are other limiting factors. Due to
these complexities, the ART should be initiated
by physicians with expertise in the use of these
agents. Long term benefit and safety must be
considered. This review aims to provide the
primary care physicians with practical
information on antiretroviral drugs that are
available for treatment.
Key words: Antiretroviral therapy - Guidelines
Drug therapy for HIV infection has changed
rapidly in the last few years. As early as 1987,
pharmacotherapy included zidovudine
monotherapy 1. Today it is recognized that
combination therapy with at least three
antiretroviral drugs is far superior. Combination
therapy such as Highly Active Antiretroviral
Therapy [HAART] can suppress viral replication,
improve immunological status, reduce
opportunistic infections and delay the
* Associate Professor
Dept. of Pediatrics
T N Medical College
Mumbai 400 008.
55
2003;5(4)325
development of resistance. In 1993, the Working
Group on ART and Medical Management of HIV
infected children was convened by National
Pediatric and Family Resource Center
[NHFRC]2. Dramatic advances in laboratory and
clinical research have evolved and
recommendations have undergone appropriate
revisions. Presently, 15 ART drugs are approved
by FDA, of which 11 have been recommended
for use in children.
Pathogenetic features of Pediatric HIV
infection
Two major developments in the mid 1990s
have contributed to the understanding and therapy
of HIV infection in children3.
a) Advent of many potent ART drugs available
for combination therapy.
b) Facility to accurately quantitate the virus
within the blood component.
It is important to recognize the biology of
the HIV virus for a better understanding of
pharmacotherapy of HIV infection4. HIV is an
enveloped single stranded RNA virus. It contains
the genes for gag, env, pol that encode for the
core nucleocapsid polypeptides, surface coated
proteins and viral enzymes reverse transcriptase,
protease respectively. The virus enters the host
cells by an interactive process between the
envelope glycoproteins, host cell CD4 molecules
and chemokine receptors. After entry into the
CD4 cell, the single stranded viral RNA is
transcribed by reverse transcriptase enzyme into
double stranded DNA. The viral DNA thus enters
the host cell nucleus and new virions are
generated. Immature virions cleave gag-pol gene
Indian Journal of Practical Pediatrics
products with the protease enzyme during their
maturation process. The mature virions are then
able to infect other host cells. An average of 10
billion virions are produced daily, with a half life
of 6 hours in infected individuals. The rate of
replenishment is high as the infected T
lymphocytes have a half life of 24 hours. Higher
number of CD4 T cells in infants and young
children provide a larger target population for
the virus thus accounting for a higher viral load
in children. The viral pool has an extensive
capacity for mutation and recombination in
response to the individuals immunity and
pharmacotherapeutic agents. Mutations occur
when errors are introduced in the viral genome
during replication. The polymerase reverse
transcriptase has 10,000 nucleotides and there is
one error for every 10,000 nucleotides. A large
pool of viral variants exists at the beginning of
the disease, many of the variants are defective
and incapable of producing infection; however,
they can be responsible for drug resistance. This
fact is accounted by using multidrug therapy early
in the course of the infection to achieve
suppression of viral replication and avoid
development of drug resistance3
Important considerations for
treating HIV infected infants and
children 2,3,4
Acquisition of infection through perinatal
exposure for many infected children.
In utero exposure to zidovudine (ZDV) and
other retroviral agents in many perinatally
infected children
Differences in evaluation of perinatal
infection
Differences in immunologic markers (e.g.
CD4+ T lymphocyte count) in young
children
Evaluation of drug dosages as changes in
pharmacokinetic parameters occur with age
56
2003;5(4)326
due to continued development, maturation
of organ systems involved in the drug
metabolism and clearance, especially in
preterm babies and neonates.
Differences in the clinical and virologic
manifestations of perinatal HIV infection
due to occurrence of primary infection in
immunologically immature individuals.
Special emphasis for adherence to treatment
in children.
Important considerations for
treating HIV infected adolescents2
Adolescents may have acquired the infection
recently through intravenous drug abuse or
the sexual route and are ideal candidates for
ART.
Special consideration for compliance and
adherence to treatment.
Doses should be prescribed based on
Tanners stages and not the age. For those
with stages I and II are given pediatric doses.
Females with stage III and males with stage
IV are given adult doses.
Females develop more fat and males develop
more muscle mass, this could alter the drug
pharmacokinetics.
Initiation and continuation of ART should
be undertaken only by personnel who have gained
expertise in the management of HIV infections
and in centers where there is a infrastructure to
manage opportunistic infections and monitor
therapy.
Antiretroviral agents
Currently available antiretroviral agents act
by inhibiting the activity of two major viral
enzymes namely reverse transcriptase (RT) and
the HIV protease. Other targets under evaluation
include the integrase inhibitors, inhibition of viral
entry (especially fusion) and viral activation 4,5,6,7
(Table 1).
 2003;5(4)327

Table 1. Antiretroviral drugs available for therapy

Drugs Formulation Pediatric dosage Side effects Remarks

Nucleoside Analogue Reverse Transcriptase Inhibitors[NRTIs]

1. Zidovudine Syrup 50mg/ml 90 -180 mg/m2/dose Anemia, leucopenia, Take with food, do not
[AZT, ZDV] Cap 100mg, QID Neonates: nausea, headache, use with d4T, reduce
Tab 300mg Oral 2mg/kg q 6hrs liver toxicity, myopathy dose in hepatic and
IV Infusion 10mg/ml renal dysfunction.

2. Lamivudine Syrup 50mg/ml 4mg/kg/dose BD, Headache, diarrhoea Prevents ZDV

[3TC] Tab 100mg, 150mg. max 150mgBD. pancreatitis, peripheral resistance, reduce dose
neuropathy. with renal dysfunction.

3. Stavudine Solution 1mg/ml 1mg/kg/dose BD Peripheral neuropathy, Elevation of hepatic

[ d4T] Cap 15,20,30,40 mg. [upto 30kg] pancreatitis, steatosis, enzymes, do not
30 -60 kg - 30 mg BD mitochondrial toxicity. combine with AZT.

4. Didanosine Solution 10mg/ml 90 -150 mg/m2/dose Nausea, diarrhoea, Rapidly degraded in

[ddI] Chewable tabs 25, 50, BD peripheral neuropathy acidic environment,
100, 150 mg. pancreatitis. To be taken on empty
stomach.

5. Zalcitabine Tab 0.375mg, 0.01mg/kg/dose TDS Fever, rash, stomatitis, Do not use with ddI,
[ddC] 0.75 mg esophageal ulcers, d4T, to be taken on
pancreatitis, peripheral empty stomach.
neuropathy, Reduce dose in renal
dysfunction.

6. Abacavir Solution 100mg/5ml 8mg/kg/dose BD Gastrointestinal, rash, Allergic reactions may

[ABC] Tab 300 mg fever, hypersensitivity, appear within 6 weeks
lactic acidosis, respira of starting therapy and
tory symptoms. resolve within 24 - 48
hours of stopping
therapy.

NonNucleoside Reverse Transcriptase Inhibitors[ NNRTIs]

1. Nevirapine Suspension: 50mg/ 120 -200 mg/m2/dose Rash, fever, nausea, Discontinue drug in
[NVP] 5ml Tab 200 mg. BD use OD for first headache, hepatitis case of severe rash
14 days.

2. Delaviridine Tab 100mg. Not known precisely Rash, headache Should be taken with
[DLV] an acidic beverage.

2. Efavirenz Cap 50, 100, 200 mg. Wt10 -15 kg , 200mg Rash, insomnia, confu Avoid high fat foods,
[EFV] Wt 15 - 20 kg, 250mg sion, euphoria, should be given at bed
Wt 20 - 25 kg, 300mg hallucina tions, poor time.
Wt 25 - 32 kg, 350mg concentration, stomach
Wt 32 - 40kg, 400mg discomfort, elevated
Wt > 40 kg , 600mg liver enzymes.
Taken OD
contd.
57
Indian Journal of Practical Pediatrics 2003;5(4)328

Table 1 - contd.
Drugs Formulation Pediatric dosage Side effects Remarks
Protease Inhibitors[PI]
1. Ritonavir Solution 400mg/5ml. 350 - 400mg/m2/dose Nausea, vomiting, Should be taken with
[RTV] Cap 100 mg BD bitter taste, abdominal food, increase dose
pain, paresthesia, slowly, drug should be
elevated liver enzymes refrigerated.
and cholesterol.
2. Saquinavir Hard gel cap 200mg 33mg/kg[max 1200mg Diarrhoea, nausea, in Take within 2 hours of
[SQV] Soft gel cap 200mg of soft gel] TDS somnia, headache, a full meal. Refrigerate
hepatotoxicity for long term storage.
3. Nelfinavir Oral powder 50mg/ 25mg/kg TDS or Diarrhoea, nausea, hyperglycemia, rash.
[NFV] scoop ful Tab 250mg. 55mg/kg BD flatulence, abdominal Hepatotoxicity,
pain,diabetes, To be taken with a
light snack/meal.
4. Indinavir Cap 200, 400 mg. 500mg/m2/dose TDS. Stomach discomfort, Take on empty stom
[IDV ] Max 800mg TDS. headache, crystalluria, ach or low fat snack.
nephrolithiasis, raised Ensure good
indirect bilirubin, hydration.
hemolytic anemia.
5. Amprenavir Soln 75mg/ml Soln 22.5 mg/kg BD Gastrointestinal , rash , Not to be given with
[VX478] Cap 50,150 mg. Cap 20 -25 mg/kg BD paresthesia, depression antacids, enquire about
sulfa allergy prior to
starting the drug.
6. Lopinavir Oral soln Wt <15 kg 12mg/kg Gastrointestinal, rash, Rifampicin increases
+Ritonavir 400mg Lopinavir + of Lopinavir BD elevated serum lipids, the metabolism of
100mg Ritonavir Wt > 15 kg 10mg/kg liver enzymes, amylase lopinavir , not to be
/5 ml Cap 133.33mg of Lopinavir BD and glucose. used concomittantly.
Lopinavir + 300mg/m2
33.3 mg Ritonavir Lopinavir BD-

Long term side effects of NRTIs have been associated with damage to the mitochondria. This damage may cause low
red and white cell counts, muscle pain, wasting. New NRTI Emcitrabine and NNRTI Emivirine are being evaluated. Adefovir
and Tenofovir diisoproxil fumerate are nucleotide agents. They inhibit HIV RT enzyme without the initial step of
phosphorylation. Long term side effects of PIs include changes in blood sugar levels, development of diabetes, elevations in
blood fat levels, lipodystrophy. There could be fat deposits in the abdomen, back of shoulders as well as loss of fat in the
arms, legs and face. Perianal abscesses are also known to occur.

1. Reverse Transcriptase Inhibitors (RTIs)
The RTIs primarily act via inhibition of HIV
reverse transcriptase, the enzyme that catalyses
the conversion of HIV RNA into double stranded
DNA. Enzyme inhibition results in termination
of the DNA chain and therapy reduces viral
replication. This class of agents is further divided
58
into nucleoside RTIs, non-nucleoside RTIs and
nucleotide RTIs.
a) Nucleoside RTIs (NRTIs)
They contain faulty versions of nucleotides,
which are used by RT enzyme to convert RNA
to DNA. The new DNA cannot build correctly
and virus production is arrested. Resistance to

this class of drug is due to the development of
mutations in codons of the RT gene. Cross
resistance among this group of drugs results from
multiple mutations in the RT gene.
b) Non-nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
They bind at different sites on the RT
enzymes, and are potent inhibitors of the RT
enzyme. They are active against the nucleoside
reverse transcriptase inhibitor-resistant strains.
2. Protease Inhibitors (PIs)
They inhibit the HIV protease, an enzyme
required for cleavage of viral polyprotein
precursors and subsequent generation of
functional HIV proteins. The virus copies its own
genetic code into the host cells DNA, thereby
creating new copies of HIV virus. Once the viral
DNA is inside a T cell DNA, the cell produces a
long strand of genetic material that must be cut
and put together correctly to form new copies.
Cutting this strand requires protease.
Principles of treatment of pediatric HIV
Infection
Determine the goals/ of therapy and discuss
them with parents and the patient (if old enough)
clearly before initiation of therapy. The aim is to
make the plasma viral load undetectable so that
maximal inhibition of viral replication is
achieved, to slow the disease progress and to
minimize the development of drug resistance 8,9,10
1. Ideally all children with HIV infection
should be offered specific ART irrespective
of their clinical status, CD4 counts or HIV
RNA copies . Immediate side effects of the
drugs, long term toxicities, high cost of
therapy and monitoring are major limiting
factors.
2. All drugs approved for adults, can be used
in children; though specific pediatric
59
2003;5(4)329
pharmacokinetic studies and effects on
growth and development are not clearly
defined.
3. Early initiation of appropriate therapy is
beneficial as it slows the deterioration of
immune function, delays progression of the
disease and reduces the incidence of
opportunistic infections.
4. Monotherapy is contraindicated as it may
result in incomplete suppression of HIV
replication and thereby promote
development of drug resistance. ZDV
monotherapy as prophylaxis, is indicated for
6 weeks in neonates born to HIV positive
mothers, but once the presence of HIV
infection is proven in the baby, monotherapy
is changed to combination therapy.
5. ART is most beneficial in patients who are
treatment naive and are initiated with the
most potent regimen. The combination of
two nucleoside RT inhibitors and a protease
inhibitor has become the gold standard of
therapy.
6. Although complete suppression of viral
replication in the plasma can be achieved
with most potent drug combinations, plasma
represents only 1% of the total body viral
burden. In some patients one may only
manage to keep the viral load below 5000
copies/ml.
7. Therapy is not curative and has to be
continued life long even if the CD4 T
lymphocyte counts are normal and HIV
RNA is undetectable in the blood. When
therapy is discontinued, there can be a
resurgence of the viral load from the long
lasting cellular reservoirs of the virus.
When to initiate ART ? (Table2)
Most decisions regarding the initiation of
ART are based on viral load and CD4 cell
Indian Journal of Practical Pediatrics 2003;5(4)330

determination. Potent therapy can at least partially
restore pathogen specific immunity to recall
antigens and naive CD4+ cells can be restored
gradually with prolonged virus suppression.
Therapy is recommended for10
a) All patients with symptomatic established
HIV infection and advanced HIV disease
(CD4 cell count < 200 cells/mm3).
b) CD4 cell counts < 350 cells/mm3 irrespective
of HIV RNA level.
c) Plasma viral load of > 30,000 copies/ml
regardless of CD4 cell count.
d) Both plasma HIV RNA levels in the 5000 to
30,000 copies/ml range and CD4 cell counts
between 350 to 500/mm3 .
e) When CD4 cell counts > 500 cells/mm3 and
viral load < 5000 copies/ml, the risk of
disease progression is slow over next 3 to 5
years. Such patients should be monitored
closely for CD4 cell counts and HIV RNA
to diagnose disease progression.
f) Consider therapy when CD4 cell count > 500
cells/mm3 but viral load is 5000 to 30,000
copies/ml.
g) No definite recommendations can be made
for those with intermediate viral load levels
and CD4 cell counts between 350 and 500
cells/mm3.
Acute treatment of a serious opportunistic
infection takes precedence over ART initiation.
Recommendations by the Working Group
on ART and Medical Management of HIV
Infected Children are summarized in Table 2.

Table 2. Indications for initiation of ART in children with HIV infection2

Clinical symptoms associated with HIV infection (i.e., clinical categories A, B, or C)
Evidence of immune suppression, indicated by CD4+ T cell absolute number or percentage
(i.e., immune category 2 or 3)
Age < 12 months - regardless of clinical, immunologic, or virologic status **.
For asymptomatic children aged > 1 year with normal immune status, two options can be
considered:
Option 1: Initiate therapy - regardless of age or symptom status.
Option 2: Defer treatment in situations in which the risk for clinical disease progression
is low and other factors (i.e., concern for the durability of response, safety, and adherence)
favor postponing treatment. In such cases, the health-care provider should regularly
monitor virologic, immunologic, and clinical status. Factors to be considered in deciding
to initiate therapy include the following:
High or increasing HIV RNA copy number.
Rapidly declining CD4+ T cell number or percentage to values approaching
those indicative of moderate immune suppression (i.e., immune category 2)
Development of clinical symptoms.
**
The Working Group recognizes that clinical trial data documenting therapeutic benefit from this approach are not
currently available, and information on pharmacokinetics in infants under age 3-6 months is limited. This recommendation
is based on expert opinion.

60
 2003;5(4)331

Table 3. Recommended Antiretroviral Regimens for initial therapy of HIV

infection in children
Strongly recommended
Clinical trial evidence of clinical benefit and/or sustained suppression of HIV replication in adults
and/or children.
One highly active protease inhibitors (nelfinavir or ritonavir) plus two nucleoside analogue reverse
transcriptase inhibitors.
Recommended dual NRTI combinations: the most data on use in children are available for
the combinations of ZDV and ddI, ZDV and lamivudine (3TC), and stavudine (d4T) and
ddI. More limited data are available for the combinations of d4T and 3TC and ZDV and
ddC.
For children who can swallow capsules: the non-nucleoside reverse trasncriptase inhibitor
(NNRTI) efavirenz (SustivaTM) plus two NRTIs , or efavirenz (Sustiva) plus nelfinavir and
one NRTI.
Recommended as an alternative
Clinical trial evidence of suppression of HIV replication, but 1) durability may be less in adults and/
or children than with strongly recommended regimens or may not yet be defined; or 2) evidence of
efficacy may not outweigh potential adverse consequences (i.e., toxicity, drug interactions, cost,
etc); 3) experience in infants and children is limited.
NVP and two NRTIs.
ABC in combination with ZDV and 3TC.
Lopinavir/ritonavir with two NRTIs or one NRTI and NNRTI.
IDV or SQV soft gel capsule with two NRTIs for children who can swallow capsules.
Offered only in special circumstances
Clinical trial evidence of either 1) virologic suppression that is less durable than for the strongly
recommended or alternative regimes; or 2) data are preliminary or inconclusive for use as initial
therapy but may be reasonably offered in special circumstances.
Two NRTIs.
APV in combination with two NRTIs or ABC.
Not recommended
Evidence against use because 1) overlapping toxicity may occur; and/or 2) use may be virologically
undesirable.
Any monotherapy. [except in neonates born to HIV positive mothers, ZDV is given for 6 weeks.]
d4T and ZDV
ddC and ddI
ddC and d4T
ddC and 3TC
ddC is not available commercially as a liquid preparation. There are currently no data on appropriate dosage of EFV
in children under age three years.

61
Indian Journal of Practical Pediatrics
What drug combinations to use 2,3,8,9,10 (Table3).
Monotherapy usually results in only a 0.5
to 1.5 log reduction of plasma RNA and due to
rapid development of resistance, is never
recommended. Nucleoside analog combinations
rarely achieve durable suppression of viral
replication and are therefore not recommended.
Dual nucleoside combinations are the backbone
of most potent regimens. The combinations used
are ZDV + 3TC, d4T + ddI, d4T + 3TC, ZDV +
ddI. The three nucleoside RT inhibitor
combination of 3TC, ZDV and Abacavir has been
found to be potent initially, though long term
studies are awaited. These three drugs can be
given as a single pill. The combination of two
nucleoside RT inhibitors and a PI has become
the gold standard of treatment. The initial
mutations seen with Nelfinavir failure are not
associated with resistance to other PIs and
Ritonavir Saquinavir and Ritonavir Indinavir
can then be used. Addition of a small dose of
Indinavir improves the pharmacokinetics of
Saquinavir and Amprenavir. The combination of
two nucleoside RT inhibitors and Efavirenz or
two nucleoside RT inhibitors and Nevirapine is
equally potent as 2 NRTIs + PI. There is less
information using Delavirdine as initial therapy.
Monitoring during ART 8,9,10
An adherence rate of at least 95% is essential
for optimal results. Barriers such as number,
timing of dose, number and size of pills, food
restrictions and adverse effects should be
considered when planning drug regimens.
Minimum of two CD4+ cell counts and two HIV
RNA measurements done a month apart should
be obtained prior to initiation of therapy.
Infections and vaccinations can lower the CD4
counts. The tests should be done from the same
laboratory. A one to two log decrease in viral
load is taken as an indication of positive drug
effect. A decrease of > 0.5 logs (three fold
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2003;5(4)332
change) is needed to overcome variability of test.
Failure to achieve the target level of < 50 copies/
ml or 10 fold decrease from the base line by 8 -
12 weeks should raise concerns about poor
adherence, improper drug absorption or drug
resistance. HIV RNA levels are to be monitored
within 1 month of initiation of therapy or change,
monthly until the goal of therapy is reached and
then every 3 to 4 months. Rise in the CD4+ cell
count during therapy reflects at least partial
immune system reconstitution.
When to change therapy ? 2,8,9,10
Reasons for changing drugs in ART are
a) Drug failure, b) Adverse effects, c) Regimen
inconvenience.
Drug failure is defined as:
Less than a 10 fold decrease (one log) from
baseline HIV RNA levels in spite of
receiving potent treatment for 8 to 12 weeks
of therapy.
Detectable HIV RNA levels after 4 to 6
months of therapy.
Repeated detection of HIV RNA in patients
who had undetectable levels following
initiation of therapy.
Levels of HIV RNA between 50 and 500
copies/ml are associated with higher risk of
resistance than levels below 50 copies/ml.
Therapy change based on only CD4+ cell
response is not recommended.
Drug failure is essentially seen with non-
adherence, sub-therapeutic drug levels, non
potent regimens.
If an individual drug in a regimen is changed
to reduce toxicity or for convenience, the full
regimen must be reviewed for potency, resistance
and drug interactions.
 2003;5(4)333

Table 4. Considerations for changing Antiretroviral therapy for HIV infected

children2
Virologic considerations *
Less than a minimally acceptable virologic response after 8 to 12 weeks of therapy. For children
receiving antiretroviral therapy with two NRTIs and a PI, such a response is defined as a less
than tenfold (1.0 log10) decrease from baseline HIV RNA levels. For children who are receiving
less potent antiretroviral therapy (i.e., dual NRTI combinations), an insufficient response is defined
as a less than fivefold (0.7 log10) decrease in HIV RNA levels from baseline.
HIV RNA not suppressed to undetectable levels after four to six months of antiretroviral therapy.
Repeated detection of HIV RNA in children who initially responded to antiretroviral therapy
with undetectable levels.
A reproducible increase in HIV RNA copy number among children who have had a substantial
HIV RNA response but still have low levels of detectable HIV RNA. Such an increase would
warrant change in therapy if, after initiation of the therapeutic regimen, a greater than threefold
(0.5 log10) increase in copy number in children aged > 2 years and greater than fivefold (0.7
log10) increase is observed in children aged < 2 years.
Immunologic considerations *
Change in immunologic classification .
For children with CD4+ T cell percentages of < 15% (i.e., those in immune category 3), a persistent
decline of five percentiles or more in CD4+ T cell percentage (i.e., from 15% to 10%).
A rapid and substantial decrease in absolute CD4+ T cell count (i.e., >30% decline in < 6 months).
Clinical considerations
Progressive neurodevelopmental deterioration.
Growth failure defined as persistent decline in weight-growth velocity despite adequate nutritional
support and without other explanation.
Disease progression defined as advancement from one pediatric clinical category to another
(i.e., from clinical category A to clinical category B). **
* At least two measurements (taken one week apart) should be performed before considering a change in therapy.
The initial HIV RNA level of the child at the start of therapy and the level achieved with therapy should be considered
when contemplating potential drug changes. For example, an immediate change in therapy may not be warranted if there
is a sustained 1.5 to 2.0 log10 decrease in HIV RNA copy number, even if RNA remains detectable at low levels.
More frequent evaluation of HIV RNA levels should be considered if the HIV RNA increase is limited (i.e., if when
using a HIV RNA assay with a lower limit of detection of 1,000 copies/mL, there is a <0.7 log10 increase from undetectable
to approximately 5,000 copies/mL in an infant aged < 2 years).
Minimal changes in CD4+ T cell percentile that may result in change in immunologic category (i.e., from 26% to 24%,
or 16% to 14%) may not be as concerning as a rapid substantial change in CD4+ percentile within the same immunologic
category (i.e., a drop from 35% to 25%).
** In patients with stable immunologic and virologic parameters, progression from one category to another may not represent
an indication to change therapy.
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Indian Journal of Practical Pediatrics
Changing the regimen: (Table 4)
In the absence of virologic failure
For adverse effects or intolerance substitute
the individual drug.
In case of NNRTI induced rash, substitution
with other NNRTIs must be monitored
because of risk of shared toxicity.
In case of Abacavir induced hypersensitivity,
the drug should be discontinued and
rechallenge deferred due to severe toxicity
and fatal reactions.
Due to virologic failure
In patients having detectable, but low levels
of HIV RNA after a few months of potent
therapy and without identified resistance to
drugs in the current regimen, addition of a
new drug (i.e. intensification) could be an
alternative to complete change.
Whenever a decision is made to change a
given regimen, at least 2 drugs (preferably
all 3) should be replaced.
While the NRTIs can be replaced by other
drugs from the same class, the same does
not hold true for the PI or NNRTIs because
of significant cross-resistance amongst other
drugs of these classes.
Three options are another PI, combination
of 2 PIs, an NNRTI and another PI.
Should therapy be stopped ?
Based on clinical and immunologic benefit,
it is reasonable to continue treatment as long as
possible.
Indications for changing therapy are as
follows:
a) Toxicity or intolerance
HIV RNA suppressed below target (< 50
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2003;5(4)334
copies/ml) or still above target but fewer than
8-16 weeks of therapy. (Change the
offending agent)
HIV RNA above target (> 50 copies/ml)
more than 8-16 weeks on therapy or prior
success.(Change the entire regimen)
b) Difficulty with adherence
HIV RNA suppressed below target, but
adherence problems present, or HIV RNA
above target but less than 8-16 weeks of
therapy. (Change to simplified regimen with
equal potency, may substitute single drug.)
HIV RNA above target, more than 8-16
weeks therapy or prior success, change entire
regimen.
c) Virologic failure
Failure to reach target viral load within 8-
16 weeks of therapy, continue current
regimen, assess adherence, consider
intensification.
Failure to reach target viral load within 24
to 36 weeks of therapy or prior success but
now confirmed drug failure. Change entire
regimen, 3 new drugs and a new class of
antiretrovirals should be used.
Resistance testing and Cross Resistance 10
Two measures are available for resistance
testing:
Genotyping testing: These assays amplify
the HIV-1 PR and RT genes from viral RNA
in plasma and then use automated DNA
sequencing of the entire PR and RT genes.
Phenotyping testing: Susceptibility of the
HIV -1 to inhibition by a particular drug is
determined.Drug required to inhibit the viral
production in vitro by 50%, 90%, 95%, is
tested, such assays can easily determine
cross resistance

Cross resistance within the three classes of
medications is usual. Cross-resistance among PIs
is important; strains resistant to Indinavir tend to
be resistant to Ritonavir. Two new PIs should be
used. Patients who have received Nelfinavir may
respond well to Ritonavir Saquinavir or
Ritonavir Indinavir. There is almost complete
cross resistance among available NNRTIs. Cross
resistance among the NRTIs is more variable.
Resistance to 3TC appears rapidly, point mutation
at position 184 of the RT gene confers high level
resistance. Resistance to ZDV is a gradual
process, appearance of multiple ZDV resistance
mutations confers high level resistance; these
strains are also resistant to d4T. Viruses with high
level resistance to ZDV and 3TC are usually
resistant to Abacavir. There is little cross-
resistance among ddI, ddC and ZDV. It is
difficult to demonstrate d4T resistance. Broad
resistance among nucleoside analogs is seen with
mutation at codon 151 and insertion mutation at
codon 69.
TB medications ART Drug Interactions:10
The most problematic drug interactions
occur between Rifampicin and PIs or NNRTIs.
Interactions are less pronounced with Rifabutin
and therefore it is a safe alternative to Rifampicin.
No significant drug interactions are noted
between TB medications and NRTIs, except that
ddI should be dosed 1 hour apart due to its antacid
buffer. There is an increased risk of neuropathy
if ddC and INH are used together. Ethambutol,
Pyrazinamide and the Flouroquinolones have no
known cyp3A4 effect and hence no major
interactions with antiretrovirals.
Other modalities of therapy and newer
drugs 2, 9
Newer treatment options under trial are as
follows:
Integrase Inhibitors e.g. ARITT and Fusion
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2003;5(4)335
Inhibitors e.g. Pentafuside (T-20) which
prevent fusion of the HIV virus with target
cells by binding to surface protein gp41 are
being studied at length.
Hydroxyurea is a ribonucleotide reductase
inhibitor. It reduces the cellular pool of
endogenous deoxynucleotide triphosphates
and improves the uptake and utilization of
nucleoside analogs. It inhibits HIV DNA
synthesis and is myelosuppressive and
reduces CD4 cell counts.
Benzamide compounds interfere with
zincfinger proteins that are essential for viral
packaging and replication.
Chemokines which interfere with co-
receptors involved in HIV infection e.g.
CCR5, CXCR4 are being evaluated.
The immune system can be assisted using
broad-spectrum recovery with cytokines
such as Interleukin IL2 or Proleukin. This
stimulates the production of T4 cells. The
cytokines regulate the immune system and
stimulate or inhibit the growth and activity
of various immune cells. Proleukin is used
in the form of high (15 million units
everyday IV), intermediate (9 million units
everyday IV) and low (3 million units
everyday IV) dose regimens for 5 days. The
course is repeated every 3 weeks.
Another approach uses therapeutic vaccines.
This approach attempts to teach a persons
immune system to fight a virus long after it
has infected the host. The candidate for this
kind of therapy is Remune or Salk Vaccine
(HIV-I Immunogen) or AG1661. The HIV
virus has been altered and killed so that it
will not cause damage to the immune system.
It is a dead form of the virus and the key
protein gp120 is missing. It can enhance the
immune response when given in the dose of
1 ml every 3 months.
Indian Journal of Practical Pediatrics
Routine intravenous immune globulin
(IVIG) therapy is also recommended in
combination with antiviral agents for
children only for the following :-
[i] hypogammaglobulinemia (IgG < 250
mg/dl, 2.5 g/L)
[ii] recurrent serious bacterial infections
(defined as 2 or more serious infections
in one year).
[iii] children who fail to form antibodies to
common antigens.
[iv] treatment of parvovirus B19 infections.
[v] treatment of thrombocytopenia
[vi] single dose for children exposed to
measles.
Dose used is 400 mg/kg/dose every 4 weeks,
and 600 mg/kg/dose every 4 weeks for
bronchiectasis.
References
1. Gogtay J. Antiretroviral therapy. In:
HIV infection in women and children. Eds,
Merchant R, Damania K, B J Wadia Hospital,
Mumbai, 1999; pp 148 -152.
2. Guidelines for the Use of Antiretroviral Agents
in Pediatric HIV Infection by The Working
Group on ART and Medical Management of
HIV Infected Children convened by National
Pediatric and Family HIV Resource Center
NEWS AND NOTES
PALS COURSE
Date: 6th and 7th December 2003
Venue: Dayanand Medical College, Ludhiana.
Address for Correspondence:
Dr.Daljeet Singh, Professor and Head, Department of Pediatrics,
Dayanand Medical College, Ludhiana.
Email: utaaldrdaljit@rediffmail.com Phone: 0161-2472794
66
2003;5(4)336
[NHPRC], Health Resources and Services
Administration [HRSA], and National Institute
of Health[NIH] . http://www.aidsinfo.nih.gov/
guidelines/pediatric/html_pediatric, 14 Dec,
2001.
3. Palumbo P E . Antiretroviral therapy of HIV
infection in children. Pediatr Clin N Am. 2000;
47: (1): 155 -169.
4. Rongkavillit C, Asmar B I. Antiretroviral drugs
in Pediatrics. Indian J Pediatr 2001; 68(7):
641-648.
5. Ritchie D J. Antiretroviral agents. In Manual
of HIV Therapeutics, chapter 5, 2nd Edn. Ed
Powderly W G. Williams and Wilkins, 2001;
pp 33-47.
6. Tashima KT, Flanigan T P. Antiretroviral
therapy in the year 2000. Infect Dis Clin N Am
2000; 14(4): 827 - 847.
7. Report of Committee on Infectious Diseases.
Antiretroviral therapy In : Antimicrobial agents
and related therapy. Red Book, 25 th edn,
American Academy of Pediatrics[AAP], 2000;
pp 678 -692.
8. Kaul D A , Patel J A . Management of Pediatric
HIV infection. Indian J Pediatr, 2001; 68(7):
623 - 632.
9. Singh S. Human immunodeficiency virus
infection . Indian Pediatr, 2000; 37(12) 1328 -
1340.
10. Powderly W G. Antiretroviral therapy. In:
Manual of HIV Therapeutics, 2 nd edn. Ed
Powderly W G. Williams and Wilkins, 2001;
pp 48 - 60.

HIV INFECTION
PREVENTION OF MOTHER TO
CHILD TRANSMISSION OF HIV
* Nitin K Shah
** Khyati Mehta
*** Mamta Manglani
Abstract: Nearly 4 million people are living with
HIV infection in India today. Six states namely
Maharashtra, Tamil Nadu, Andhra Pradesh,
Karnataka, Manipur and Nagaland have high
prevalence rates for HIV infection defined as
more than 1% HIV prevalence amongst pregnant
women tested during sentinel surveillance
conducted in the ante-natal clinics. 28 million
deliveries occur in India annually. At a national
average of 0.5% HIV prevalence in mothers
attending the ANC clinics, 1.4 lakhs of deliveries
occur in HIV infected mothers annually and
without any intervention 30% of these exposed
babies will become HIV infected. This means
approximately 40000 babies get HIV infection
through vertical route in India annually. This
figure could be more if the national average
prevalence is more than 0.5%. What is required
is an effective and feasible program to prevent
mother to child transmission. Voluntary testing
and counseling must be available to all the
mothers attending the ANC clinics. Those who
are detected HIV infected must receive anti-
* Hon. Pediatrician,
U.H.C., LTMG Hospital, Mumbai
Programme Co-ordinator, IAP Project on
Child to Adolescent HIV/AIDS
** Pediatrician, Mumbai
*** Professor and Head,
Div. of Pediatric Hematology,
Dept. of Pediatrics, LTMG Hospital, Mumbai
67
2003;5(4)337
retroviral prophylaxis, safe delivery care and
counseling on the feeding of the baby. Besides
this, the focus must be turned on primary
prevention of HIV infection in the wouldbe
mothers with mass education and last but not the
least care and concern towards those who are
already infected. This article discusses further
the various modalities available for prevention
of mother to child transmission (PMTCT).
Key words: Childhood HIV, Mother to child
transmission, Indian feasibility study
Magnitude of the problem
World over, 30-40 million people are
expected to be HIV infected. 30-40% of HIV
cases are in women of childbearing age and 10-
15% of cases occur in the pediatric age group. It
is estimated that daily 2000 new pediatric HIV
cases occur world over, of which 200 cases occur
in India. Mother to child transmission accounts
for 80-90% of pediatric cases, which can be easily
prevented1. Of the 28 million deliveries occurring
in India annually, 0.84 lakh deliveries occur in
HIV positive mothers at a national average of
0.3% prevalence of HIV in pregnant women.
Without any intervention, 30% of these babies
will become HIV infected i.e. annually 24,000
babies are HIV infected in India by vertical
transmission. If this prevalence reaches 1%, it
will lead to a lakh of babies infected at birth.
Efficacy of vertical transmission
Vertical transmission occurs due to infection
of the baby by maternal blood, cervico-vaginal
secretions or via breast milk. The baby gets
infected either due to transplacental hemorrhage
or due to infection via umbilical cord or via oral
Indian Journal of Practical Pediatrics
and GI (gastrointestinal) mucosa while
swallowing infected amniotic fluid. The
incidence of vertical transmission is 20% in
western world, whereas it is as high as 30-40%
in developing countries. In India it has been
shown to be 30%. With the use of interventions
like elective caesarean section, antiretroviral
drugs and replacement feeding instead of breast-
feeding, the incidence of transmission has
dropped from 20% to 8% or even less in the
western world.
Factors that affect the efficacy of vertical
transmission
The efficacy of vertical transmission
depends on various factors. These include
maternal factors, type of delivery, factors in
newborn, breast-feeding and the type of interven-
tions used to decrease the rate of transmission.
Maternal factors
Vertical transmission rate is high when the
mother has recently seroconverted or in those
who are in late stage of HIV disease, as both are
likely to have high viral load. More the viral load
in the mother, more is the rate of vertical
transmission. Except one study, all others have
shown that transmission does occur even when
maternal viral load is low or is undetectable.
Hence, no level of viral load is safe as far as
vertical transmission is concerned. Presence of
high titre of anti-HIV antibodies in mother
protects the newborn from HIV infection to some
extent, as these antibodies pass transplacentally
to the baby. Many studies have shown higher
chances of vertical transmission when mothers
were malnourished as they have low anti-HIV
antibody levels. Vitamin A deficiency in mother
is also associated with increased chances of
vertical transmission. Presence of other STDs
especially with bleeding lesions of cervix or
vagina lead to increased chances of
contamination of birth canal and increased
68
2003;5(4)338
chances of vertical transmission. Some viral
characteristics, like highly replicating virus in
mother, are associated with increased vertical
transmission. In western countries mothers who
used illicit intravenous drugs are known to have
increased vertical transmission.
Type of delivery
Infected vaginal and cervical secretions as
well as the maternal blood have been the source
of HIV infections for the baby. HIV has been
isolated from vaginal as well as cervical
secretions of at least 50% of HIV- infected
women. Logically longer the time the baby
remains in contact with birth canal, more will be
the chances of HIV infection. Various studies
have shown increased vertical transmission rates
in babies delivered vaginally, especially with
prolonged labour and rupture of membrane for
more than 4 hours. It is also more in the presence
of chorioamnionitis, traumatic delivery,
instrumentation during delivery and episiotomy.
In mothers with sexually transmitted diseases, the
risk is more due to increased contamination due
to open bleeding lesions. The incidence of
transmission has been shown to be 25% with
rupture of membrane for more than 4 hrs as
compared to 14% with rupture of membrane for
less than 4 hrs. This has prompted many
investigators to study the effect of elective LSCS
on HIV transmission.
Prematurity
Prematurity is associated with an increased
rate of vertical transmission. This is probably
related to the thin skin, susceptible mucous mem-
branes and immature immune functions with
lesser transfer of maternal antibodies
transplacentally (before 34 weeks of gestation).
Postnatal factors
The main post-natal factor involved in
transmission is breast milk which is expected to

lead to 14% extra risk of transmission over and
above other factors.
Timing of vertical transmission
Exact timing of vertical transmission varies
from case to case. It can occur in utero as early
as 15-20 weeks (as aborted fetuses have been
shown to be infected with HIV). In addition, some
workers have described HIV dysmorphism in
some cases characterized by craniofacial
dysmorphisms and congenital heart disease. But
the fact that most of the HIV infected babies are
normal at birth, suggests that the infection is
transmitted most commonly in the last trimester,
during labour and via breast milk postnatally.
This is also evident by the fact that interventions
to decrease vertical transmission are able to block
it by 50-65%.
The relative frequency of timing at which
transmission occurs is as follows. Of the 30% of
babies who get infected vertically, 2% get
infected early in gestation and 3% late in gestation
mainly in last month of gestation, 15% get
infected during labour, 5% get infected in early
post partum period and 5% in late post-partum
period2. The Pediatric Virology Committee of the
AIDS Clinical Trial has proposed definitions for
determining the timing of infection (in-utero
versus intra-partum). It is considered that a child
with a positive PCR within 48 hours of birth has
been infected in utero3. If a non- breastfed baby
who is PCR- negative at birth demonstrates a
positive PCR at 7- 90 days, the baby is considered
to have been infected during delivery. Most of
the interventions to decrease the transmission
target the late prenatal period, labour and
postnatal period to block transmission.
Prevention of mother to child transmission
(PMTCT)
PMTCT involves four strategies:
a) Measures to decrease maternal HIV cases
69
2003;5(4)339
b) Measures to decrease viral load in HIV
infected mothers e.g. AZT to mother.
c) Measures to decrease exposure of baby to
maternal fluids e.g. elective lower segment
caesarean section (LSCS) or avoiding breast-
feed.
d) Measures to decrease chances of HIV in
exposed babies e.g. AZT to baby.
Interventions to decrease MTCT
Different interventions undertaken to
prevent vertical transmission include: -
a) Antiretroviral drugs
b) Infant feeding issues
c) Elective LSCS
d) Cleaning of birth canal during delivery
e) Vitamin A prophylaxis
f) Immunotherapy
A) Anti-Retroviral Drugs
The most successful intervention decreasing
vertical transmission is the use of antiretroviral
drugs during pregnancy, labour and post-natally
to the mother and baby. Most extensively and
successfully used drug is AZT (used as mono-
therapy since 1994). Even nevirapine has been
used successfully as mono-therapy since 1999.
Of late, combination of two drugs or more has
been used successfully bringing down the vertical
transmission to below 2%. These drugs act by
reducing the viral load in the mother and act as
post exposure prophylaxis in the newborn. There
are ethical dilemmas like creating orphans by
preventing HIV in the peri-natally exposed babies
by these measures. However 70% of babies born
to HIV infected mothers naturally escape the
infection and are at the risk of being orphans
sooner or later. It will be more unethical to let a
child contract HIV when it could have been
prevented.
Indian Journal of Practical Pediatrics
There are many trials done in this regards
like PACTG 076 protocol, Thai-CDC protocol,
Uganda protocol using nevirapine, French
perinatal cohort study, Cote d ivoire study,
PETRA study, SAINT Study, etc. We will discuss
some of the important studies. Most studies target
the last months of gestation, labour and post-
partum period of 1 week for the mother and for 6
weeks to the baby postnatally.
1) PACTG 076 Protocol
This multicentric study by the Pediatric
AIDS Clinical Trial Group was done in 1994 in
USA and France4. HIV positive mothers who
were AZT (Zidovudine) naive had CD4+ counts
more than 200 were enrolled between 14-35
weeks of gestation. They were not enrolled before
14 weeks due to fear of teratogenicity of AZT
and not enrolled after 35 weeks as it was
considered too late to start AZT. All enrolled
mothers were given AZT in the dose of 100 mg
5 times a day from the day of enrolment till the
onset of labour. On the day of delivery they were
given intravenous AZT in the dose of 1 mg/kg/
hr in drip form till delivery. After delivery the
baby was put on oral AZT in the dose of 8 mg/
kg/day in 4 divided doses, starting the first dose
within 12 hrs of birth and it was continued for 6
weeks. All babies were born by elective LSCS at
38 weeks of gestation and all the babies were
given formula feeds and breast-feeding was not
allowed at all. The results of vertical transmission
were compared with matched control group of
mother and child pairs who were given placebo
instead of AZT in the same schedule. The results
at 18 months showed the transmission rate to be
26% in placebo group and 8% in AZT group,
this means 68% efficacy of AZT in preventing
mother to child transmission. This has been the
best efficacy reported by any study so far. In fact
with the interim reports, the trial was stopped
prematurely as it was unethical to continue
placebo group. All the subsequent trials are
compared with the 076 trial.
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2003;5(4)340
Though 076 protocol is ideal, it has many
practical problems for developing countries.
Firstly, it is a lengthy protocol both for mother
and baby. It will lead to increased cost, decreased
compliance and hence failure in majority. In
developed countries the cost of this protocol is
estimated to be US$ 1000/- per patient. It starts
very early in gestation which means mothers have
to register early and all mothers need to be tested
for HIV, which are difficult in developing
countries. It not only needs intravenous AZT
during labour, a formulation which is not
available in India, but also elective LSCS, which
is not available and safe all over the country. Only
top feeding in babies is allowed which may not
be desirable, safe, affordable and acceptable to
mothers. Hence there is a need for shorter, less
complicated protocols for developing countries.
2) Thai-CDC Protocol (short course AZT
protocol)
This protocol was tried in Bangkok,
Thailand in 1998, in collaboration with CDC
keeping in mind the need for simple, short term
AZT protocol for developing countries5. In this
protocol, HIV positive mothers were enrolled at
34 weeks of gestation and were given AZT orally
in the dose of 300 mg BD till the onset of labour.
During labour, they were given oral AZT in the
dose of 300 mg 3 hourly till delivery to a
maximum of 4 doses. LSCS was not mandatory.
However, all babies were given formula feeds
and breast-feeding was not allowed. Baby was
not given AZT at all. At 3 months after birth the
transmission rate was 18.9% in placebo group
and 9.4% in AZT group. It means AZT in such a
short course still had 50% efficacy in preventing
vertical transmission. This may appear 15% less
than 076 protocol but it has many advantages.
Firstly, it is a short protocol and that too only for
mother for just one month. This is affordable,
and acceptable to many leading to better
compliance. Mother could be enrolled even if she

is registered as late as 35 weeks of gestation. It
was not mandatory to do LSCS. Only oral AZT
was continued during labour and not IV AZT.
The only drawback was avoidance of breast-
feeding. Yet this protocol is ideally suited for
developing countries.
In India during phase I feasibility study of
AZT, this protocol was used with only
modification being that informed choice was
given to the mother to decide the type of feeding
to the baby after counseling. It was a multi-centric
study done in 11 medical colleges in 5 states of
high prevalence involving 192,474 deliveries, of
which 171,471 (89.1%) were offered pretest
counseling, 103,681 (60.5%) accepted screening,
1,724 (1.7%) were found HIV positive, of which
726 (42.1%) were put on AZT. 427 newborns
were tested for PCR and 43 (10%) of them were
found positive by 2 months of age (personal
communication). Only 22% of the mothers chose
to breast-feed their babies. This proves that in a
short term follow up, this protocol had efficacy
of 66% as it brought down the transmission from
30% to 10%. It will be interesting to know the
transmission on long term follow up till 18
months as those who are infected via breast-feed
will be picked up later.
Problems with Thai protocol: Though this
protocol brought down the cost from US$1000/-
for the 076 protocol to US$ 50/- for this protocol,
it still has its own problems in countries like ours.
We still need to give AZT for one month, which
may be difficult as the compliance may not be
good. It also makes it expensive to supply drug
for one month. The other thing is that the mother
still needs to enroll in the antenatal clinic before
35 weeks of gestation, which is not always the
case, as many mothers come late or even during
labour straightaway. Lastly breast-feeding was
not allowed in Thai protocol, which again poses
problem in a country like ours where replacement
feeding may be dangerous and where breast-
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2003;5(4)341
feeding is the norm. Hence, there is a need to
have alternate protocol, which further decreases
the period of medication and may be useful even
in those who present straight in labour and
secondly a protocol that may allow breast-feeding
to be continued.
There are various protocols which have
looked at the efficacy when breast-feeding is
allowed. There are two protocols that have looked
at this problem, the Cote d lvoire Abedjan study
and the Cote d lvoire and Buskina Faso study
(DITRAME study) 6,7. Both the protocols in
essence used AZT for a month as in the Thai
protocol and allowed breast-feeding to continue
in addition. Both the protocols showed similar
efficacy of 37%-38% on long term follow up,
which is less than with the Thai protocol.
Nevirapine protocol (HIV NET 012)
Nevirapine as mono-therapy was used in this
protocol in Uganda in 19998. Nevirapine was
compared against short course of AZT (as trying
placebo will be unethical). Nevirapine was given
as single dose of 200 mg orally at the onset of
labour to be taken at home with onset of first
labour pain. The baby was given single dose of
nevirapine in the dose of 2 mg/kg orally within
48-72 hours of birth while in hospital. This was
compared with another group given AZT in the
dose of 600 mg at onset of labour followed by
300 mg 3 hourly till delivery and then to the baby
in the dose of 4 mg/kg/dose BD for 7 days.
Elective LSCS was not mandatory and breast-
feeding was allowed. The initial results are very
encouraging. At 6-8 weeks the HIV transmission
rate was 21.3% in AZT group and 11.9% in
nevirapine group and at 14-16 weeks it was
25.1% in AZT group and 13.1 in nevirapine
group. This gives efficacy of around 50%, which
is same as Thai protocol. However, at 12 months
the transmission in nevirapine group was 16%
and in AZT group 24% showing only 35%
Indian Journal of Practical Pediatrics
efficacy. Yet there are many advantages of this
protocol. Firstly it involves only a single dose to
mother at the onset of labour and a single dose to
baby while in hospital. This makes the protocol
very cost effective and acceptable with good
compliance. It can also be administered to
mothers who register at the last moment or even
to unregistered cases. In fact some think that in
areas with HIV prevalence as high as 15-25%,
like in some African countries, this protocol
should be offered to all those come for delivery
and who are not tested so that it will benefit many.
However, it may be unethical to do so. Elective
LSCS is not mandatory and breast-feeding is
allowed in this protocol. This makes it acceptable
to many in developing countries. One needs to
await further results on long- term follow-up.
Secondly, the success of this protocol needs to
be duplicated at some other centers to prove the
efficacy and safety.
In India, during phase II feasibility study,
nevirapine was used as stated above giving
informed choice to the mother to decide the type
of feeding to the baby after counselling. It is a
multi-centric study done in 11 medical colleges
in 5 states of high prevalence involving 45,924
deliveries, of which 38,984 (84.9%) were offered
pretest counseling, 35,472 (91.0%) accepted
screening, 464 (1.6%) were found HIV positive
during ANC and 81 (4.5%) were found positive
during labour (who benefited from this protocol).
305 (70.6%) mother-child pairs were put on
Nevirapine. 48 newborns were tested for PCR
and 4 (8.3%) of them were found positive by 2
months of age. This proves that in a short term
follow up this protocol had efficacy of 66% as it
brought down the transmission from 30% to
8.8%. It will be interesting to know the
transmission on long term follow up till 18
months as those who are infected via breast-feeds
will be picked up later. 54.9% of mothers opted
for breast-feeding and only 20.8% were breast-
feeding at 4 months (personal communication).
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2003;5(4)342
Long term safety of AZT
Short-term follow up during O76 protocol
has shown less than 4% chances of toxicities like
anemia, neutropenia or skin rash in mothers as
well as babies given AZT. These side effects like
anemia are transient and disappear by 4-6 weeks.
In France, mitochondrial dysfunction has been
reported to occur in a small number of infants
exposed in-utero or neonatally to nucleoside
reverse transcriptase inhibitor9. Such a side- effect
has not been noted in any other study or reviews
of earlier studies. Lastly though there is
theoretical fear of inducing drug resistance by
using a single agent for a short study period, the
advantages of these protocols far outweigh such
miniscule risks. Many times there is ethical
dilemma when the mother is offered the drug
under the protocol to prevent MTCT but once
the drug is stopped after the protocol is
completed, she is not offered any treatment free
and she cannot afford to take the anti-retro viral
drugs on her own. It appears that the mother is
solely given the drug for the sake of prevention
of HIV in the babies and she herself is not looked
after. However, it is worth it even ethically, as
we are preventing HIV in the newborn.
PACTG 219 is a long term follow up study
of the babies enrolled in 076 protocol originally
and are planned to be followed up till 21 years of
age10. The interim results show that at median
follow up of 4.6 years the growth parameters,
cognitive function, ophthalmic evaluation;
immunological function and ECG are similar in
AZT group as in placebo group. This proves long
-term safety of AZT.
Protocols containing combination drugs
In the West, protocols containing 2 or more
drugs are used and that has reduced the vertical
transmission rate to < 5%. PETRA study had 4
arms using AZT plus 3TC in various combination
for the mother and the newborn11. The efficacy

at best was 21% when minimum 1-month of
drugs were given to the mother. The efficacy fell
to 7% when shorter courses were used. SAINT
trial was done in South Africa in 200012. HIV
positive mothers were assigned to one of the two
treatment arms. In Arm A, mothers were given
nevirapine in dose of 200 mg orally at onset of
labour and at 24-48 hrs after delivery and the
baby was given 2 mg/kg orally at 24-48 hrs after
delivery. In Arm B multiple doses of AZT + 3TC
were given during labour and for 1 week and also
to baby for 1 week (like in PETRA Arm B). The
results at 6-12 weeks showed transmission rate
of 12.7% in Arm A (similar to Uganda Protocol
HIV NET O12) and 9.5% in Arm B (similar to
PETRA Arm B).
B) HIV and infant feeding - A big dilemma
Breast-feeds (BF) or Replacement feeds (RF)
The biggest dilemma faced by a pediatrician
in managing HIV patients is to decide whether
to allow breast-feeding by HIV positive mothers.
Various questions that come in mind include what
is the risk of HIV infection with breast- feeding?
How long to breast-feed? What is the alternative
and what are the risks of replacement feeds in
our set-up? Whose right is it to choose what feeds
the newborn should receive?
HIV and breast-feeding
HIV is transmitted by breast milk as proved
by many studies. Firstly both the free and cell
bound HIV has been isolated from human breast
milk. Free HIV can infect CD4+ cells lining the
GI tract of baby. Infected maternal mononuclear
cells present in breast milk can pass through
mucous membranes of baby and infect the baby.
Transmission to child is shown to occur from the
mother infected with HIV post-natally and who
breast-fed the infant. Lastly, studies done have
compared rate of vertical transmission in those
babies who were breast- fed compared to those
who were exclusively top- fed and showed that
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2003;5(4)343
there is 14% extra risk related to breast-feeding
over and above other factors.
HIV in human breast milk
HIV has been shown in high titers in
colostrum as well as in breast milk for first 4 days
after delivery. Some have shown it to be present
for as long as 4-6 months or even beyond that
after delivery. Vitamin A deficiency in mother
leads to increased titers of HIV in breast milk.
Other conditions like breast abscess, mastitis or
sore nipple can lead to contamination of breast
milk with mothers blood.
As against this, there are some protective
factors present in human milk that protect the
baby against HIV infection. Goldman et al have
shown presence of glycoproteins and other
substances like mucins, lysozymes, lactoferrins,
T cells, complements and secretory leukocyte
protease inhibitor (SLIP) etc that decrease
binding of pathogenic organisms to GI tract
epithelial cells and decrease chances of
transmission via breast milk, including that of
HIV. Presence of anti-HIV antibodies especially
anti-gp120, anti-gp40, IgG as well as anticore
IgM and IgA antibodies in human milk have been
shown by Western Blot technique. This can also
decrease the infection of baby.
HIV infected mothers and breast-feeding
Most studies have shown that there is 14%
extra risk of HIV transmission by breast milk,
which means that it almost, doubles the rate of
vertical transmission. The risk depends on various
factors. Colostrum has higher viral load and
higher risk of infection. But it also contains higher
antibody level. The risk is increased by obvious
contamination by maternal blood due to cracked
or sore nipple. But the most important factor is
the length of breast-feeding.
There is a cumulative increase in
transmission of HIV, as length for which breast-
Indian Journal of Practical Pediatrics
feeding increases, as shown in the Malawi study
done in 199913. The risk was estimated to be 0.7%
per month for 0-6 months i.e. cumulative risk of
4.2% in this period. It was 0.6% per month
between 6-12 months i.e. cumulative risk of 3.6%
during this period. It decreased to 0.3% per month
between 12-18 months i.e. cumulative risk of
5.8% in this period and 0.2% per month between
18-26 months i.e. cumulative 1.2% for that
period. The total cumulative risk is 10.2% if
breast-feeding is continued till 2 years and is 4.2%
if breast-feeding is continued till 6 months. Hence
it will be optimal to exclusively breast feed till 6
months and then abruptly wean off completely
in next 10-15 days.
Exclusive breast-feeding will avoid
problems of infection related with top feeding. It
is cost effective, ideal in developing countries. It
will also avoid stigma associated with not breast-
feeding due to HIV. It is accepted by > 90% in
developing countries. However, as discussed later
mixed feeding should be avoided and the
compliance to absolutely exclusive breast-
feeding in general population is estimated to be
only 22-35%. Hence, it is the duty of counselor
and pediatrician to ensure that it is exclusive
breast-feeding and not mixed feeding.
HIV and replacement feeding (RF)
Replacement feeding may appear as a
logical choice in HIV infected mothers. However,
it has its own problems. Replacement feeding,
especially bottle-feeding, is associated with
higher infections like acute respiratory infections
(ARI) and diarrhea, especially in countries with
high infant mortality rate (IMR). A study in Brazil
showed that the overall mortality due to ARI was
4 times more and that due to diarrhea 14 times
more in top-fed babies as compared to breast-
fed babies14. A recent study done in South Africa
compared babies born to HIV positive mothers
who were breast fed with those who were formula
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2003;5(4)344
fed15. This was done in urban set up with under
five mortality rate (UFMR) of 70/100,000. The
mothers were educated to an average of 8th
standard and they all had access to safe water
supply. This was very similar setting as ours. 2
year follow up results showed that the
transmission of HIV at 2 years was 19.1% in
formula fed babies and 35.7% in breast fed
babies, yet the mortality at 2 years was 20% in
formula fed babies and 24.4% in breast fed
babies. This proves that the gains in the form of
less HIV infection in top fed babies was set off
by higher mortality due to ARI and diarrhea in
both HIV infected and non-infected babies.
Besides this there is problem of breast milk
spillage and leakage if mother chooses to give
replacement feeds. There is social stigmatization
if the mother does not breast feed the baby in
countries where breast-feeding is the norm. It also
involves issues of education of mother, socio-
economic condition and access to potable water
to make safe and correct replacement feeds.
Lastly, comes the question of affordability. The
mother may tend to dilute feeds, which is
dangerous. At national level in India, it will be
enormous task to spend 75 million rupees per
month to provide formula feeds to all babies born
to HIV positive mothers. Hence, if the mother
chooses not to breast- feed, it is better to give
cows milk with spoon rather than formula feeds,
as it is cheaper, easily available and more
acceptable. One should again ensure exclusive
replacement feeding if it is chosen by mother and
not mixed feeding.
HIV and mixed feeding
A study done in Durban, South Africa in
1999 compared HIV transmission in exclusively
breast fed babies, exclusively top fed babies and
babies given mixed feeding i.e. babies given
breast feeds plus any other liquids, born to HIV
infected mothers 16. The results at 3 months

showed that the HIV transmission was 14.6% in
exclusively breast fed babies, 18.8% in
exclusively top fed babies, and 24.1% in babies
given mixed feeding. At this stage, it appeared
that the transmission was less in exclusively
breast fed babies than in exclusively top fed
babies and both were significantly better than
mixed feeding. Long term follow up results at
15 months showed that HIV transmission was
24.7% in exclusively breast fed babies, 19.4% in
exclusively top fed babies and 35% in babies
given mixed feeding. This showed that over long
term the advantage of exclusive breast-feeding
seems to be negated as compared to exclusive
top feeding. However both were significantly
better than mixed feeding.
HIV is absorbed via the gut of newborn. A
baby on top feeding has leaky gut allowing
increased chance of HIV absorption. Hence, a
child who is on mixed feeding will have worst
outcome. Besides such a child is exposed to evils
of both HIV as well as other infections related to
top feeding. Hence, HIV infected mother should
not give mixed feeding. If she decides to breast
feed, it should be exclusive breast-feeding and if
she decides to give replacement feeding, it should
be exclusive replacement feeds.
Policy
Policy regarding infant feeding by HIV
infected mothers at individual level and at
national level should take into consideration the
merits and the demerits of breast milk
replacement feeds, education level, socio-
economic status, health statistics, accessibility to
safe water, affordability and HIV prevalence. It
should be an informed choice made by the mother
after proper counseling. This process should start
right during pregnancy and continue after
delivery. The role of counselor and pediatrician
should be to give correct information on various
options and they should not be biased or
75
2003;5(4)345
judgmental towards any option. The informed
choice opted by the mother should be respected
even if it appears incongruent socio-
economically. In the West, mothers prefer not to
breast-feed. In India, the choice should be left to
mother. But whatever the choice be, it should
either be exclusive breast-feeding or exclusive
replacement feeding and not mixed feeding.
C) Safe delivery practices
i) Elective LSCS: Many studies have shown that
elective LSCS done at 38 weeks before rupture
of membrane or onset of labour reduces the risk
of HIV transmission by 20-50%. One recent study
done by Swiss group compared the effect on
vertical transmission of AZT alone as per O76
protocol, elective LSCS alone, combined elective
LSCS and AZT and no interventions. They found
that the chances of HIV transmission with
combined AZT and elective LSCS were 0%, with
elective LSCS alone 8%, with AZT alone 17%
and with no intervention at all 20%17.
Elective LSCS reduces the transplacental
hemorrhage occurring during labour, reduces the
length of exposure of the baby to vagino-cervical
secretions or maternal blood, reduces the
quantum of infective material, reduces
swallowing of infected material by baby and
reduces chances of ascending infection to baby.
All this reduces HIV transmission.
However, elective LSCS in all HIV infected
mothers is an enormous task. It may increase
maternal mortality, as it may not be safe in some
parts of our country. It will also increase the cost
of therapy. Hence, the decision has to be
individualized depending upon the set-up and
stage of HIV in the mother.
ii) Vaginal delivery: Vaginal delivery leads to
more chances of HIV infection. The Swiss study
showed that the risk of transmission of HIV was
6% with LSCS and 20% with vaginal delivery.
Indian Journal of Practical Pediatrics
The chances increased to 29-31% if interventions
are done during vaginal delivery like traumatic
delivery or episiotomy. Hence episiotomy and
other procedures should be avoided during
vaginal delivery in HIV infected mothers.
iii) Miscellaneous: Cleaning of birth canal with
virucidal / antiseptic agents like chlorhexidine led
to a decrease in the rate of vertical transmission
in a study done in South Africa.18. However other
studies have failed to get the desired results.
Hence, a search for the ideal agent still contin-
ues. Interestingly, all these studies showed
decrease in mortality in babies due to decreased
incidence of neonatal sepsis. Hence cleaning of
birth canal is beneficial both ways. Vitamin A
was found to be beneficial in an earlier study,
however a recent study from Malawi in South
Africa has shown no benefit of vitamin A
supplementation in HIV infected mothers on
vertical transmission19. Similarly the use of anti-
malarial drugs in endemic areas have shown
benefits in some studies.
Phases of PMTCT
PMTCT involves 5 phases:
Phase I: This phase involves giving information
on voluntary counseling and testing, infant
feeding, option of medical termination of
pregnancy, family planning measures, problems
of orphans, etc. to mother who is HIV positive.
This will go a long way in preventing pregnancies
or decrease the exposure of babies to maternal
HIV.
Phase II: This phase involves giving prophylaxis
to mother and child, which includes antiretroviral
drugs to mother and baby and use of safe delivery
practices like elective LSCS and non-traumatic
vaginal delivery.
Phase III: This phase involves issues related to
replacement feeds versus breast feeds.
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2003;5(4)346
Phase alpha: This phase involves primary
prevention of HIV in mothers and society. This
includes HIV education, avoiding high-risk
behaviors, treatment of sexually transmitted
diseases, imparting life skills etc.
Phase omega: This phase includes care and
support of already HIV infected mothers and
babies, social support and economical support,
etc.
References
1. NACO. Estimation of HIV infection among
adult population - HIV sentinel round 2000-
2001
2. Rouzioux C, et al. Estimated timing of mother-
to-child human immunodeficiency virus type
1 (HIV-1) transmission by use of a Markov
model. Am J Epidemiol 1995; 142(12); 1330-
1337
3. Bryson YJ, et al. Proposed definitions for in
utero versus intrapartum transmission of
HIV 1. N Engl J Med 1992; 327(17); 1246-
1247
4. Connor EM, Sperling RS, Gelber R, et al.
Reduction of maternal-infant transmission of
human immunodeficiency virus type 1 with
zidovudine treatment. N Engl J Med 1994; 331:
1173-1180.
5. Schaffer N. Short course zidovudine for
perinatal HIV-1 transmission in Bangkok,
Thailand : a randomised controlled trial. Lancet
1999; 353: 773-780.
6. Wiktor SZ, Ekpini E, Katon JH, et al. Short
course oral zidovudine for prevention of mother
to child transmission of HIV-I in Abedjan, Cote
dl Ivoire : a randomised trial. Lancet 1999;
353: 781-785.
7. Dabis F, Msellati P, Meda N, et al. 6 month
efficacy, tolerance and acceptability of a short
regimen of oral zidovudine to reduce vertical
transmission of HIV in breast fed children in
Cote d Ivoire and Burkina Faso: a double blind
placebo-controlled multicentre trial. Lancet
1999; 353: 786-792.

8. HIV NET 012. Prophylaxis for maternal
transmission of HIV-1. Lancet 1999; 354:
795-802.
9. Blanche S, Tardieu M, Rustin P, et al. Persistent
mitochondrial dysfunction and perinatal
exposure to antiretroviral nucleoside analogues.
Lancet 1999; 354:1084- 1089.
10. Culnane. Lack of long term effects of in utero
exposure to zidovudine among uninfected
children to HIV infected women. JAMA 1999;
281: 151-157.
11. Gray G. Early and late efficacy of three short
ZDV/3TC combination regimens to prevent
mother-to-child transmission of HIV-1.
Abstract LbOr5; 13th International AIDS
Conference, Durban, South Africa, 9-14 July
2000
12. Moodley D. The SAINT Trial: nevirapine
(NVP) versus zidovudine (ZDV) + lamivudine
(3TC) in prevention of peripartum HIV
Transmission. 13th International AIDS
Conference. Durban, South Africa. July 2001.
(Abstract LbOr2).
13. Miotti PG, Taha TE, Kumwenda NI, et al. HIV
transmission through breastfeeding: a study in
Malawi. JAMA 1999; 282; 744-749
14. WHO Technical Consultation on behalf of the
UNFPA/UNICEF/WHO/UNAIDS Inter-
NEWS AND NOTES
XXIII ANNUAL CONVENTION NATIONAL NEONATOLOGY FORUM
ORGANISED BY N.N.F, A.P. CHAPTER
Date: 18th to 21st December 2003
Venue: Gandhi Medical College (probable), Hyderabad, Andhra Pradesh.
Address for correspondence:
Dr.M.Nagaraj Rao (or)
Organising Secretay
Srivatsava, A/29, Santosh Nagar colony (old)
Hyderabad 500 659.
Phone: 24530194.
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2003;5(4)347
Agency Task Team on Mother-To-Child
Transmission of HIV. New data on the
prevention of mother-to-child transmission of
HIV and their policy implications: Conclusions
and recommendations. Geneva, October 2000
15. Ruth Nduati, Grace John, Dorothy Mbori-
Ngacha, et al. Effect of Breastfeeding and
Formula Feeding on Transmission of HIV A
Randomized Clinical Trial. JAMA 2000; 283:
1167-1174.
16. Coutsoudis A, et al. Method of feeding and
transmission of HIV-1 from mothers to children
by 15 months of age: prospective cohort study
from Durban, South Africa. AIDS 2001; 15:
379-387.
17. Kind C, Rudin C, Seigrist C et al. Prevention
of vertical HIV transmission: additive
protective effect of elective cesarean section
and zidovudine prophylaxis. AIDS 1998; 12:
205-210.
18. Biggar RJ, Miotti PG, Taha TE, et al. Perinatal
Intervention trial in Africa: Effect of a Birth
canal cleansing intervention to prevent HIV
transmission. Lancet 1996; 347: 1647- 1650.
19. Semba RD, Miotti PG, Chiphangwi JD, et al.
Maternal Vitamin A deficiency and mother- to-
child transmission of HIV- 1. Lancet 1994; 343:
1593- 1597.
Dr.M.Dasaradha Rami Reddy
Joint Organising Secretary
Prof. of Pediatrics
Department of Pediatrics
Gandhi Hospital, Hyderabad - 500 003.
Phone: 24054366 27719594 (O)
Email: dr_malireddy@yahoo.com
Website: www.neocon2003.org
Indian Journal of Practical Pediatrics
RADIOLOGIST TALKS TO YOU
ABDOMINAL MASS
* Vijayalakshmi G
** Natarajan B
*** Ramalingam A
Abdominal mass is a serious problem in
children. About 40 % of abdominal masses were
malignant in a series in Institute of Child Health
and Hospital for Children which included
obstructive renal lesions, polycystic disease of
the kidneys and other inflammatory masses.
Quite often the mass has presented late to the
pediatrician and the symptoms may be vague
and non-specific. There is no substitute for a
good abdominal palpation. This may bring to light
some mass so that there is no delay in detection
or investigation which may affect the clinical
course of the child. Once a mass is suspected the
first imaging is with ultrasound. Ultrasound (US)
in most cases offers adequate information that
makes other intensive radiological investigations
superfluous.
Once the screening ultrasound has
demonstrated a solid tumor, a CT may be done.
CT is a useful baseline and follow-up
examination.Its main disadvantage is the
* Addl. Professor in Radiology
Department of Radiology
Kilpauk Medical College and Hospital
** Asst. Professor in Radiology
Department of Radiology
Institute of Child Health and Hospital for
Children, Chennai.
*** Addl. Professor in Radiology
Department of Radiology
Institute of Child Health and Hospital for
Children, Chennai
78
2003;5(4)348
radiation involved. If CT is not available, an IVU
can be done that will demonstrate renal function,
involvement of pelvicalyceal system and
therefore the plane of swelling whether
retroperitoneal or not.
Ultrasound will give you a number of
answers:- First of all whether a mass is present
or not. There are times when a colon loaded with
fecal matter has been mistaken for a mass.
Secondly, if a mass is present, what organ is
involved, what cavity is involved or whether a
mass extends across the diaphragm as in the case
of certain neuroblastomas. Then it will also show
content of the mass whether cystic or solid.
Ulrasound will also alert you to what vital organs
or blood vessels are at risk. In addition, it will
indicate presence or absence of hepatic spread
and involvement of lymph nodes. So, you can
reason out if the tumor can be safely removed
or should the child be first treated with
chemotherapy or radiation before surgical
intervention? Ultrasound can also be useful
for screening high-risk individuals who may
develop malignancies like Beckwith-
Wiedemann Syndrome.
Fig 1 shows a kidney with a tumor mass
confined well within. At this stage it is easy to
make out the organ of origin. Organ capsule and
fascial planes are not broken. Ultrasound shows
the mass which is of a different echotexture than
that of normal renal tissue. Look for the presence
of normal renal tissue with normal pyramids. A
mass will not show this normal appearance.
Fig 2 is the CT of another patient showing a
mass arising from the anterior surface of the
right kidney. Compare the Pelvi Calyceal System
on the right with the one on the left .Note the
 2003;5(4)349

Fig 1. Small Wilms tumor. See the rounded mass in the upper pole with normal parenchyma
in the rest of the kidney

Fig 2. Distortion of the pelvicalyceal system.- Wilms tumor

79
Indian Journal of Practical Pediatrics 2003;5(4)350

Fig 3. Large mass destroying the entire kidney

Fig 4. A solid retroperitoneal mass ( L) is seen lifting the aorta (A) and IVC anteriorly

80
 2003;5(4)351

Fig 5. A solid mass with tiny specks of calcifications.- neuroblastoma.

Fig 6. A large teratoma with big areas of calcification. Note the normal kidneys posterior to the
mass.
81
Indian Journal of Practical Pediatrics 2003;5(4)352

distortion of the pelvicalyceal system on the
right. This is an important feature you have to
look for. It is seen in both IVU and CT, where
the collecting system is outlined with contrast.
This feature will tell you that the mass is renal.
But when the tumor is very large the entire
kidney is destroyed .In the case of the patient in
Fig 3., the kidney was not visualized in US. If
the kidney is not visualized in US the next step is
to do an IVU or a contrast CT to locate the kidney
CT also showed a large mass on the left. The
kidney or any part of its collecting system was
not seen because there was no functioning renal
parenchyma to excrete the contrast. In such a
situation it is reasonable to assume that the mass
is of renal origin. The commonest renal tumor is
Wilms tumor. This is usually a solid tumor. It
may show areas of cystic degeneration. We have
seen only two cases of the renal cell carcinoma
which is extremely rare in the child .
The next common malignant tumor seen in
children is the neuroblastoma. This usually arises
from the adrenal gland but can also be seen
anywhere along the sympathetic chain. The
adrenal mass causes a characteristic displacement
of the kidney-down and outwards. It rarely
infiltrates the kidney. Look at the neuroblastoma
in Fig 4. The mass has lifted the aorta and IVC
anteriorly. Therefore this is a retroperitoneal
mass. Displacement of neighbouring organs point
to the plane of the swelling.
CT may outline the extent of masses better
but small capsular breaches that would upstage
the tumor are best seen only at surgery. Contour
irregularity in CT may suggest extrarenal
invasion. CT can also show lymphadenopathy
due to tumor spread . CT is of value in identifying
hepatic metastases while US remains the
modality of choice for showing tumor thrombus
in the IVC.
In US or CT the neuroblastoma has an
irregular outline and tiny calcifications ( Fig 5 ).
Now look at Fig 6 .Is this a neuroblastoma ?
There is a large well-defined mass with gross
calcific areas in the subhepatic region. This is a
typical picture of a teratoma mass with thick
calcifications. Contrast this with the fine
calcification of neuroblastoma. The kidneys are
intrinsically normal though the right kidney is
seen flattened against the posterior abdominal
wall. Again ,contrast this displacement with that
of a neuroblastoma.
Now you can see that US is the first imaging
modality that would help to localize the plane or
origin and decide the nature of the
mass.Detection is certain with US though extent
and calcification is better with CT.

NEWS AND NOTES

1ST NATIONAL MEET ON FLUID, ELECTROLYTES AND BLOOD GASES
Organised by IAP 2003, Nagpur
Date: November 21st , 22nd & 23rd 2003
Venue: Hotel Centre Point, Nagpur.
Address for correspondence:
Organising Chairman: Dr.Satish Deopujari
Organising Secretary: Dr.Vishram Buche
Om Child Trust Hospital,
Dharampeth Extension, North Bazaar Road,Nagpur 440 010. (M.S)
Email: vbuche@rediffmail.com.
Phone No. (Hosp)-(0712) 2534650, 2527172, (Res)-(0712) 2228276, 5614568
Mobile:098230-17254

82

PRACTITIONERS COLUMN
HEARING LOSS IN CHILDREN :
NEED FOR EARLY DETECTION
AND INTERVENTION
* Abraham K Paul
Hearing loss has considerable impact on the
overall development of the infant language
development, development of cognition,
development of social and emotional
competence.
The first year of life is a critical period for
brain development, especially development of the
auditory pathway.1 Auditory experience during
this period has profound influence on functional
development of auditory system and lack of
auditory experience can have detrimental effects.
This can be understood by this basic neuro
developmental phenomenon. At birth, the brain
has100 billion neurons and they form about 50
trillion connections. 2 The only way the
connections can be strengthened is by stimulation
both auditory and sensory. The connections
that are not used or stimulated wither away. Now
we understand the need for a constant auditory
stimulation for optimal development of auditory
system, a prerequisite for optimal development
of speech and language.
Even mild hearing loss if not detected early
can significantly retard acquisition of language
skill and untreated hearing loss of greater degree
have a measurable, even devastating effect on
speech and intellectual development.3
* Co-ordinator, Newborn Hearing Screening
Programme
Child Care Centre, Cochin 682 020
83
2003;5(4)353
In USA, UK and many other developed
countries, routine screening for hearing of all
newborns is made compulsory before discharge
from hospital. If by chance, it is not
accomplished, screening is done at the next visit,
but never later than 2 months. The incidence of
hearing loss is found to be in the range of 2 4
per thousand. This is quite high as compared to
all other screenable diseases put together (thyroid
disorders, sickle cell anemia, phenyl ketonuria).
When one takes into account the incidence of
hearing loss in high-risk babies it may be to the
tune of 1.515%.
Babies at high risk for Hearing impairment5
Neonates
1. Birth weight less than 1500 gms
2. Hyperbilirubinemia requiring exchange
transfusion
3. Bacterial meningitis
4. Apgar scores of 0 to 4 at one minute, or 0 to
6 at 5 minutes
5. Mechanical Ventilation lasting 5 days or
more
6. Ototoxic medications
7. Family history of hereditary childhood
sensorineural hearing los
8. Intrauterine infections (TORCHS)
9. Craniofacial anomalies
10. Stigmata or other findings associated with a
syndrome known to include a sensorineural
and/or conductive hearing loss.
Indian Journal of Practical Pediatrics
Infants (29 days through 2 years)
1. Speech and language delay
2. Developmental delay
3. Concern regarding hearing by parents.
4. Bacterial meningitis.
5. Recurrent or persistent otitis media with
effusion for at least 3 months.
6. Head trauma associated with loss of
consciousness or skull fracture.
The importance of early detection of hearing
loss will be understood when we explore the
results of certain studies done in this field. One
important study done is the one done at university
of Colorado in 1998, which showed that early
intervention before 6 months is critical for
optimum development of speech and language.
Even infants with severe hearing loss if
intervention was done before 6 months showed
near normal cognition and language
development.2
Even minimal hearing loss (16 25 dB loss)
is educationally significant. This is because a
youngster with mild bilateral hearing loss may
miss 20% to 30% of vital speech information if
unamplified. Many consonant sounds are heard
inconsistently (eg. the word Cup, Cat, Calf may
all be perceived as Ca) and faint and distant
speech is difficult to be understood.4 Children
with hearing impairment typically demonstrate
errors in the form, content, and the use of
language. Early detection and intervention can
reduce or prevent the impact of hearing loss on
learning. Results of recent research has shown
that many children with hearing loss are likely to
achieve normal speech and language skills by
5 years when detection and rehabilitation are
initiated before 6 months of age.
84
2003;5(4)354
Infection used to be the major causative
factor resulting in hearing loss. But with the
widespread use of various preventive
vaccinations (MMR, Hib) infection is no more
the major cause. With survival of more number
of preterm and high risk babies at neonatal
intensive care services, they dominate as the most
vulnerable group. Certain intra-uterine
infections, otitis media, medications, sudden
noise of high intensity, head trauma, infections
and certain genetic diseases may all result in
hearing loss.
Evaluation of hearing by BERA or Oto-
acoustic emission (OAE) can be performed even
in the newborn period. Various tests are also
available appropriate for older infants and
children of any age. Clapping of hands and
observing the childs response is a very crude
method and should never be resorted to as a
reliable method of hearing assessment. A test may
have to be repeated number of times or a battery
of tests may have to be done. The skill and
experience of the examiner plays an important
part in the proper evaluation and judgement. One
important point of emphasis is that all children
with speech delay should have a hearing
assessment as the preliminary test at the earliest.
The management primarily depends upon
the cause. Once correctable and surgical causes
are excluded, the cornerstone in management is
amplification of sound by use of hearing aids (as
early as 5-6 months of age). Children with
profound deafness who derive negligible benefit
from conventional amplification with hearing
aids may be considered for cochlear implants
(electronic prosthetic device that is surgically
placed in the cochlear portion of inner ear to
provide useful sound perception).
A total communication approach should be
attempted blending the use of hearing aids,
 2003;5(4)355

auditory training, speech therapy and in selected
cases, lip reading and sign language. By 3 years,
educators and parents should plan the educational
mode that will most suit the child school for
the deaf, special class in a regular public school
or an ordinary school.
Key message: Never miss a hearing loss, identify
hearing loss at the earliest, have hearing
assessment done in all cases of speech delay.
References
1. Yuonne S S, Karan Jo Doyle, Jean K. Moore et
al. The case for early identification of Hearing
Loss in Children. Auditory System
Development of Speech Perception and
Hearing Pediat Clin N Am 1999; 46; 1-2.
2. Marios P. Downs, Christine Yoshinaga, Itano
et al. The efficiency of Early Identification and
Intervention for Children with Hearing
Impairment Pediat Clin N Am 1999; 46; 79-
82.
3. Yoshinaga - Hano C. Efficiency of Early
identifiction and early intervention. Semin Hear
1995; 16(2): 115-123.
4. Noel D, Matkin, Amy M, Wilcox et al.
Considerations in the Education of Children
with Hearing Loss. Pediat Clin N Am 1999;
46; 143.

NEWS AND NOTES

37TH NATIONAL CONVENTION OF THE INDIAN COLLEGE OF

ALLERGY, ASTHMA AND APPLIED IMMUNOLOGY
Date: 12, 13 & 14 December 2003
Venue: Bangalore, Karnataka.
Address for correspondence:
Dr.H.Paramesh Prof. Shripad N. Agashe Ms.Elizabeth Cherian
Chairman Chairman Secretary
Organising Committee Scientific Committee Organising Committee
Lakeside Medical Center & Hospital
33/4, Meanee Avenue Road,
Near ulsoor Lake, Bangalore 560 042.
Ph: 080-5304276/5566738/5366723/5512934
Fax: 080-5303677
Email: dr_paramesh1@yahoo.com
elizabeth_cherian@yahoo.com

PEDINEUROCON-2003
V NATIONAL PEDIATRIC NEUROLOGICAL CONFERENCE
Date: 22nd and 23rd November 2003
Venue: SMS Convention Centre, Hotel Rambagh Palace, Jaipur.
Address for correspondence:
Dr.Ashok Gupta Dr.H.S.Bhasin
Organising President Organising Secretary
476 A/5, Vyas Marg, Raja Park, Jaipur, Rajasthan 302 004.
Email: pedineurocon2003@hotmail.com, Phone: 0141-2621962, Mobile: 3126087

85
Indian Journal of Practical Pediatrics 2003;5(4)356

CASE STUDY

CLEIDOCRANIAL DYSOSTOSIS characterized by absence or rudimentary

development of the clavicles, abnormal shape of
* Sujatha L the skull and depression of the sagital suture,
** Lakshminarayanan S frontal bossing and many wormian bones. The
Srivenkateswaran
Venkatesh AL
Cleidocranial Dysostosis is a disorder
characterized by generalized dysplasia of osseous
and dental tissues commonly resulting in defects
in the skull, clavicle and teeth. Over 500 cases
have been reported worldwide in literature1.
A 6 year old male child was brought with
history of failure to thrive, retarded growth and
recurrent respiratory infections. There was no
other positive history. On examination, the child
had a large calvarium with a small face and
shallow nasal bridge. Teeth abnormalities were
Fig. 1. Large calvarium, open anterior
present. Patient was able to closely approximate
fontanelle and wormian bones.
his shoulders over the chest. He was short
statured.
X-ray studies: Skull-frontal and lateral view:
large head, open anterior and posterior fontanelle
and shows presence of wormian bones. Chest:
complete absence of both clavicles, small and
high scapulae, short ribs directed obliquely
downwards.
Discussion
Cleidocranial Dysostosis is a familial
autosomal dominant dysplasia due to delayed
ossification of midline structures particularly of
membranous bone. It is a developmental defect
* Consultant Radiologist
** Consultant Pediatrician Fig. 2. Complete absence of clavicle. Small
Sri Venkateshwar Hospital high scapulae. Short ribs directed obliquely
Tiruvarur, downwards.
86
 2003;5(4)357

fontanelle may remain open until adulthood. References

Dental features include maleruption, absent or
delayed eruption of deciduous and permanent
teeth and small maxillae 2. There will be
hypoplasia or absence of clavicle (defective
development usually of the lateral portion or outer
portion), narrow thorax which may cause
respiratory distress in newborn and small
scapulae, hemivertebrae and supernumerary ribs.
There may be short and flat femoral neck and a
wide pubis symphysis. The case is presented
because of its rarity and its full fledged form.
1. Christine M Hall and Donald G. Shaw. Skeletal
dysplasia and malformation syndromes.
Diagnostic Radiology. Ed R.G.Grainger /
Allison D.J, 3rd Edition. Churchill Livingstone
1999; 1767-68.
2. Lees W.R. Congenital skeletal anomalies;
skeletal dysplasias: chromosomal disorders. In:
Text Book of Radiology and Imaging. 6th Edn.
Ed David Sutton, Churchill Livingstone, 1998:
12-13.

NEWS AND NOTES

XV NATIONAL PEDIATRIC NEPHROLOGY CONFERENCE

Date: November 21st and 22nd, 2003
Venue: Scudder Auditorium, Christian Medical College, Bagayam, Vellore, Tamilnadu.
Registration Fees:
Status Before 15.08.03 Before 30.09.03 Spot
Delegate 900/- 1,200/- 1,800/-
Student* 800/- 1,100/- 1,600/-
Accompanying Person 700/- 1,000/- 1,500/-
* PG Students would be required to send a certificate from their professors that they are bona-fide
students.
Address for correspondence:
Dr. Indira Agarwal,
Organising Secretary,
XV National Pediatric Nephrology Conference
Department of Child Health
Christian Medical College, Vellore - 632 004. Tamilnadu, India.
Phone: +91(0416) 2222102 / 2223603 Extn.: 3348, Fax: +91 0416 2232035 / 2232103
Emal: child2@cmcvellore.ac.in

87
Indian Journal of Practical Pediatrics 2003;5(4)358

CASE STUDY

VAGINAL VOIDING AS A CAUSE done under image intensification. The voiding

OF RECURRENT URINARY pictures showed widening of the urethra due to
TRACT INFECTION urine pooling in the vagina with a normal bladder
(Fig. 1). Post void film showed retention of
* Sripathi V contrast in the vagina indicative of urine being
** Vijayakumar M retained (Fig. 2). The child was treated with
appropriate antibiotics and educated to void urine
Vaginal voiding (post void dribbling) is one
among the minor dysfunctional disorder such as
daytime urinary frequency syndrome, giggle
incontinence and stress incontinence. This occurs
in girls after they have finished voiding and is
due to urine accumulation in the lower vagina.
When the child stands up urine trickles out of
the vagina into the undergarment. The problem
is commonly due to poor posture during
micturition, in obese children or in a child with
female hypospadias wherein the urethra opens
into the anterior wall of the vagina at a variable
distance from the vulval outlet. Here we are
presenting a clinical problem of a child with Fig. 1 Voiding phase of MCU showing
vaginal voiding presenting as recurrent UTI. widening of urethra. This is due to urine
pooling in vagina
A 5-year-old female child presented with
recurrent symptoms of low-grade fever, dysuria,
increased frequency and hematuria of about 3
years duration. There has been episodes of
frequent wetting of the undergarment after the
completion of urination. It was attributed to the
bladder infection. Renal function including urine
analysis was unrewarding. Urine culture was
positive for E.coli. Clinical examination revealed
a dense adhesion of the labia minora, which was
separated. A micturating cystourethrogram was

* Consultant Urologist,
** Consultant Pediatric Nephrologist, Fig 2. Post void film of MCU showing urine
Kanchi Kamakoti CHILDS Trust Hospital,
retained in the vagina after bladder empyting
Chennai 600 034.

88
 2003;5(4)359

by keeping the thighs wide apart and to have
complete voiding. The best way to achieve is to
reverse the position of sitting on the Western or
Indian toilet. This reverse position achieves
separation of the thighs and avoids refluxing of
the urine into the vagina, which could predispose
to incontinence, stasis of urine and infection.
In conclusion, careful clinical examination
for labial adhesion, urethral opening
abnormalities and a history of urinary
incontinence will help to identify the cause of
UTI and minimize investigations.

BOOK REVIEW

Title : Clinical evaluation of newborns, infants and children

Author : Dr. S.Sushama Bai
Review : This book titled Clinical evaluation of newborns, infants and children is an
ideal book to be included in the armamentarium of books on clinical examination, where we have
only very few books in this category. Book begins with a good start of how a doctor should be.
The sections are well organized and all authors of these topics justified it to the fullest extent. The
sections family interview to start with and the concluding section How to communicate deal
with practical points. It is nice that examination of newborns also included. Authors have taken
care to include relevant bedside tests also then and there. The interpretation of electocardiogram is
one such attempt, which should be appreciated. We find this book as a good collection of certain
reference values, measurements and differential diagnosis etc, for which we have to refer many
books when in need. All the topics have been written in a simple and clear manner with many
illustrations, which makes understanding better.
Publisher : Panicker Publications
Amalagiri P.O.,
Kottayam,
Kerala, 686 036.
Price : Rs.215/-

89
Indian Journal of Practical Pediatrics
CASE STUDY
PODOPHYLLIN POISONING
* Harish V Sutrave
** Ravisekar CV
** Kumarasamy K
** Sathyamurthy B
** Venkataraman P
*** Vasanthamallika TK
Introduction
Poisoning in children is a global problem.
Morbidity and mortality due to accidental
poisoning is a serious challenge to pediatricians.
In India next to malnutrition and infection,
poisoning poses a major threat to the lives of our
children. Knowledge of the nature of the poison,
lethal dose and antidotes is a must for every
physician.
Podophyllin is a dried resin from the roots
and rhizomes of Podophyllum peltatum
(Mandrake or May apple plant) the North
American variety; and Podophyllum emodi the
Indian variety1. Active ingredients are lignans
including podophyllotoxins, alpha-peltatin and
beta- peltatin1 .
Case report
A 2 year old female child presented to us
with complaints of vomiting, fever, altered
sensorium of one day duration. Alleged to have
ingested 3-4 ml of podowart solution at her
* Post graduate
** Assistant Professor
*** Additional Professor
Institute of Child Health and Hospital for
Children, Chennai - 8.
90
2003;5(4)360
neighbours house the previous day. Child had
repeated episodes of vomiting and altered
sensorium after ingestion with one episode of
loose stool. On admission she was withdrawing
to pain only. Her vitals were stable and there was
no shock or seizures. She was given supportive
management and CSF analysis was done which
was normal. Her sensorium improved to the
extent of mild drowsiness with unsteady gait on
day 2 of admission. Gait improved on day 4 and
she was able to take oral feeds by then. Her
hemoglobin was 9.6gm/dl with hypochromic
microcytic anemia and liver function tests were
normal. With no neurological deficit she was
discharged on day 6. This will be the second
reported case in Indian literature. Western
literature has reported a 2 year child of
podophyllin poisoning2.
Discussion
Podophyllotoxin and its derivatives are
potent cytotoxic agents that inhibit cell mitosis
and deoxyribonucleic acid (DNA) synthesis in a
manner similar to that of colchicines2 a potent
spindle poison 2. Podophyllin is used as an
ointment for plantar warts1. Routes of exposure
are oral, dermal, inhalational and occular1. Local
effects are pruritus, irritation, urticaria, skin
necrosis, bleeding and scarring of tissue.
Systemic effects of poisoning are tachycardia,
cardiac arrhythmias, hypotension, cardiovascular
collapse, tachypnoea, respiratory failure,
pneumonitis, pulmonary oedema, confusion,
lethargy, coma, convulsions, peripheral
neuropathy, paralytic ileus, rhabdomyolysis,
myoglobinuria, nausea and vomiting, abdominal
pain, diarrhoea, elevation of hepatic enzymes,
 2003;5(4)361

oliguria, cystitis, renal failure, fetal death, REFERENCES

abortion, premature labour, fetal malformation,
leucocytosis, followed by leucopenia, anemia,
thrombocyto penia, pancytopenia and metabolic
acidosis1,2,3,4. Death generally results from the
cerebral, cardiovascular, renal, or haematological
complications. Management involves performing
gastric lavage if patient is seen early and
administering activated charcoal. In case of
topical contact wash with soap and water.
Maintain vital signs. Hemoperfusion should be
used for severe systemic poisoning since it has
been shown to be effective in reducing the plasma
fraction of podophyllum toxin5. No antidote is
available5.
1. Miller RA. Podophyllin. Int J Dermatol, 1985;
24: 491-497
2. Filley CM, Radford NRG, Lacy JR, Heitner
MA, Earnest MP. Neurological manifestations
of podophyllin toxicity. Neurology. 1982;32:
308-311.
3. Clark ANG, Parsonage MJ. A case of
podophyllin poisoning with involvment of
nervous system. BMJ 1957; 2: 1155-1157.
4. Sudha Rudrappa, L.Vijayadeva. Podophyllin
poisoning. Indian Pediatrics 2002; 39: 598-599.
5. Heath A, Mellstrans T, Alham J (1982).
Treatment of podophyllin poisoning with resin
hemoperfusion. Human toxicol, 1:373-378.

NEWS AND NOTES

3RD JHARKHAND STATE PEDICON

Date: 22nd and 23rd November 2003

Venue: Bokaro Steel City, Jharkhand.

Registration: Up to Aug. Up to Nov. 15th Spot

Delegate Rs.500/- Rs.600/- Rs.800/-

Associate Delegate Rs.300/- Rs.400/- Rs.500/-

PG. Students Rs.200/- Rs.300/- Rs.400/-

DD / Cheque may please be drawn to favour of 3rd Jharkhand State Pedicon payable at Bokaro.
Please add Rs.30/- for outstation cheque. You are requested to kindly send abstract of papers with
name and address of the presenting author and suggestion if any.

Address for Correspondence:

Dr. B.Prasad,
Organising Secretary, Qr. No.1061, Sector IV/C, Bokaro Steel City 827 004.
Phone: (06542) 247256, 232200. Email: bijayprasad_nagar@sify.com

91
Indian Journal of Practical Pediatrics 2003;5(4)362

QUESTION AND ANSWER

Q. Various pharmaceutical companies are
coming up with preparations containing both
nimesulide and paracetamol. While promoting
these, they talk of things like; paracetamol has
faster onset of action but shorter duration of
action, whereas nimesulide has delayed onset
of action but longer duration of action. So
when the effect of paracetamol starts waning,
nimesulide takes up. Is there any rationality
in this combination or is this just another
addition to the long list of irrational
combination drugs available in the market?
Dr. Madhumita Nandi,
Shajahanpur, U.P.
A. Various drugs and drug combinations are
used in the treatment of childhood fevers to
restore the disturbed hypothalamic thermostasis.
When antipyretics are indicated, traditional use
has included aspirin, paracetamol, ibuprofen and
more recently nimesulide. Even though
nimesulide has a more potent antipyretic effect
than paracetamol, combination of these two drugs
(nimesulide paracetamol) does not lead to a
synergistic or potentiated therapeutic effect1.
An ideal drug for the symptomatic treatment
of fevers in children should be short acting which
can be repeated as and when indicated , so as not
to mask the signs and symptoms of serious
illnesses in infants and children2.Logically any
drug/or combination with a prolonged antipyretic
effect should rather be considered its limitation
than an advantage. Such a fixed dose combination
will also be associated with problems such as
difficulty in dosing and a potential risks of
adverse effects like hypothermia and abnormal
liver enzymes. Thus there is no rational
justification for the paracetamol and nimesulide
combination and its use in children.
References
1. Kulkarni SK, Jain NK. Is there a rationale for
nimesulide paracetamol combination? Indian
J Pharmacol 1999;31:444-445.
2. Amdekar YK. Rational use of antipyretics.
Indian Pediatr 2003;40:541-544.
Dr. Niranjan Shendurnikar
Associate Professor of Pediatrics
Medical College Baroda 390001

NEWS AND NOTES

2nd ANNUAL PEDIATRIC PULMONOLOGY UPDATE
HOSTED JOINTLY BY IAP RESPIRATORY CHAPTER WEST BENGAL &
IAP HOWRAH DISTRICT BRANCH
Date: 2nd November 2003, Sunday. Time: 9am 5pm.
Venue: Auditorium, Ramakrishna Mission Seva Pratisthan, 99, Sarat Bose Road, Kolkata.
Faculty: Dr.G.S.Sethi, MAMC New Delhi.
Contact:
Dr.Gautam Ghosh, Phone: 24553691 / 98301-71815, Email: ghoshped@cal3.vsnl.net.in
Dr.Santanu Bhakta, Phone: 26611413 / 23594294, Email: sbhakta@cal3.vsnl.net.in
Office: CJ-296, Sector II, Salt Lake City, Kolkata 91.

92
 2003;5(4)363

AUTHOR INDEX

Abraham K Paul (354) Nitin K Shah (13) (275) (338)

Adhisivam B (163) Noel Narayanan S (229)
Akikusa JD (105) Panchapakesa Rajendran (80)
Amdekar YK (206) Parthasarathy A (80) (179) (265)
Anuj R Shah (191) Prahlad N (133)
Anuradha K (77) Preetha Prasannan (167)
Archana Kher (326) Pritesh Rathod (191)
Archana B Patel (73) Ramachandran P (154) (244)
Arpana Bhagirath (254) Rajath A (299)
Ashok S Kapse (213) Raju C Shah (191)
Ayyar SSK (141) Ramalingam A (66) (159) (233) (349)
Benjamin B (49) Ramanan AV, (105)
Bharat R Agarwal (5) Ramesh S (264)
Brajachand Singh (284) Ramesh L Renge (73)
Chourjit Singh Ksh (284) Ram Saravanan R (165)
Divya A Dave (247) Rajiv Chandra Mathur (304)
Dulari J Gandhi (247) Rewari BB (277)
Elizabeth KE (149) Revathi Raj (21)
Elizabeth John (71) Rakesh Lodha (287)
Elizabeth Mathai (93) Raveendranath S (71)
Gandhimathy Sekhar (29) Ravisekar CV (71) (361)
Geethanjali M, (77) Rinku Agarwal (315)
Gopal Subramoniam (249) Sathyamurtry B (361)
Habib Bhurwala (247) Sandeep B Bavdekar (315)
Harish V Sutrave (361) Sangeetha V (141)
Indrashekar Rao (99) Sarala Rajajee (8)
Indumathy S (244) Saranya N (111)
Isha Garg (254) Senthil Kumar KS (244)
Janani Shankar, (163) Shanthi S (244)
Jayakar Thomas (63) Saradha A Sarnaik (25)
Jayakumar (167) Sheela Bharani (247)
Joshi PL (277) Shinjini Bhatnagar (125)
Kabra SK (287) Sripathi V (359)
Kamlesh R Lala (173) Shivananda (299)
Karthikeyan AG (252) Srivenkateswaran (357)
Kishore D Phadke (254) Subramanyam L (180)
Ketan H Shah (237) Sujatha L (357)
Kulandai Kasthuri R (244) Sukumaran TU (167)
Kumarasamy R (361) Sundararaman PG (252)
Kumutha J (256) Suresh Kumar (141)
Kusumakumary P (38) Swati Y Bhave (307)
Khyati Mehta (338) Tapan Kr Ghosh (265)
Lakshmi Naryanan S (357) Thangavelu S (244)
Mathur YC (304) Thiravium Mohan (249)
Mamta Manglani (338) Tripti Pensi (277)
Mohammed Thamby (165) Varinder Singh (82)
Milind S Tullu (315) Vasanthamallika TK (71) (361)
Mrudula K Lala (173) Vasanthi D (141)
Mukesh Kumar Singh (198) Veerendra Kumar (167)
Nagamani Agarwal (254) Venkataraman P (71) (252) (361)
Nair PMC (44) (118) Venkatesh AL (357)
Nagarajan M (165) Vidyashankar CV (222)
Nammalwar BR (133) Vijayalakshmi G (66) (159) (233) (349)
Natarajan B (66) (159) (233) (349) Vijayakumar M (133) (179) (359)
Niranjan Shendurnikar (80) (198) Vijayasekaran D (57)

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SUBJECT INDEX

Approach: Recurrent bleeding (21) Laboratory evaluation: Hypertension (133)

Antinuclear antibody tests (237) Management: Acute asthma (57)
Antiretroviral therapy (326 ) Management: Complicated malaria (222)
Approach: Fever and rash(49) Management: Immunocompromized
children with cancer (25)
Approach: Persistent jaundice (256)
Metatropic dysplasia (71)
Rare case of cyanosis (244)
Neonatal metabolic screening tests (118)
Caffeys disease(165)
Neonatal progeroid syndrome
Cleidocranial dysostosis (357)
(Wiedemann-Rautenstrauch) (247)
Clinical manifestations: HIV infection in children (287)
Neurofibromatosis (167)
Clinical neurophysiology (141)
Newer cephalosporins (198)
Complete blood counts (29)
Nosocomial infections: Management issues (191)
Counselling: Pediatric HIV / AIDS (307) Opportunistic infections: Pediatric HIV disease (315)
Common dermatological problems (63) Pediatric Hematology and Oncology (5)
Crouzens Syndrome(73) Prevention of mother to child transmission: HIV (338)
Dengue haemorrhagic fever(163) Pneumonia: Treatment strategies (206)
Approach: Dengue illness (213) Podophyllin poisoning (361)
Approach: Arthritis (105) Radiologist talks to you (66) (159) (233) (349)
Diarrhoea hemolytic uremic syndrome (254) Rapid diagnostic tests (111)
Epidemiology: HIV in India (277) Recent advances: Acute lymphoblastic
General Management: HIV (304) leukemia(38)
GnRH dependent isosexual precocious Recognition: Critically ill child (154)
puberty in a girl child (252) Peripheral smear: Diagnosing difficult
Guidelines: Collection of specimens for clinical situations (8)
microbiological investigations(93) Schizencephaly (77)
Hearing loss (354) Severe acute respiratory syndrome (170)
Hypovolemic hypernatremic dehydration: (44) Smart nutrients and brain development (149)
Interpretation of laboratory investigations: Strategies: Control of infectious diseases (229)
Intrauterine infections. (99) Tips for Practising Pediatrician (173)
IV Drug abuse and HIV: North Eastern India (284) Tuberous sclerosis in newborn (249)
Laboratory diagnosis: Persistent and chronic Update component therapy (13)
diarrhoea (125)
Vaginal voiding: Recurrent urinary
Laboratory diagnosis: Pediatric HIV (299) tract infection (359)

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 2003;5(4)365

PEDICON 2004
41st NATIONAL CONFERENCE OF THE INDIAN ACADEMY OF PEDIATRICS
Healthy child - Mighty IIndia
ndia
8-11 January 2004, Chennai
Venue: Sri Ramachandra Medical College & Deemed University,
Porur, Chennai, Tamilnadu 600 116

The metropolitan city of Chennai known for its excellent hospitality and good ambience, invites
you to the 41st National Conference of the Indian Academy of Pediatrics at Sri Ramachandra
Medical College and Deemed University, Porur, Chennai between 8-11 January 2004. The theme
of the conference is Healthy child - Mighty India. The pediatricians of the city of Chennai
eagerly await to host this prestigious event after a span of 17 years by providing academic feast to
fellow pediatricians from India and abroad.
Dr. B.R. Nammalwar Dr. A. Balachandran Dr. M.P. Jeyapaul
Organising Chairman Organising Secretary Hon. Treasurer

Category Before Before Before Before From 1.12.2003

30.4.2003 30.08.2003 30.10.2003 30.11.2003 & Spot

IAP Member Rs.2300 Rs.2800 Rs.3500 Rs.4500 Rs.5500

Non IAP member Rs.2500 Rs.3000 Rs.3800 Rs.4800 Rs.6000
Accomp. person Rs.2000 Rs.2500 Rs.3000 Rs.4000 Rs.4500
PG Student # Rs.2000 Rs.2500 Rs.3000 Rs.4000 Rs.4500
Senior citizen ## Rs.2000 Rs.2500 Rs.3000 Rs.4000 Rs.4500
SAARC delegate Rs.2500 Rs.3000 Rs.3800 Rs.4800 Rs.6000
Foreign delegate US $ 200 US $ 250 US $ 350 US $ 400 US $ 500
Cancel/Refund * 70% 60% 50% 30% Nil

# PG student should submit the bonafide certificate

## Senior citizen > 65 years
* Refund will be done one month after the conference
** Details regarding the preconference workshops (on 7.1.2004) will be intimated later
For further details contact:
Dr. A. Balachandran,
Organising Secretary, PEDICON 2004,
IAP - TNSC Flat, Ground Floor, F Blook, Halls Towers,
56 (Old No.33) Halls Raod, Egmore, Chennai 600 008.
Phone: 044-28190032, 28191524, 52145280 Email: pedicon2004@yahoo.com
Web: www.pedicon 2004.com
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Indian Journal of Practical Pediatrics 2003;5(4)366

REGISTRATIONFORM
PEDICON2004
41st NATIONAL CONFERENCE OF INDIAN ACADEMY OF PEDIATRICS
Healthy child - Mighty IIndia
ndia
Venue: Sri Ramachandra Medical College & Deemed University, Porur, Chennai 600 116
Delegates Title [ ] Dr. [ ] Prof. [ ] Mr. [ ] Mrs. [ ] Ms. IAP Membership No...............................
Name ......................................................................................................................................................
Mailing address .....................................................................................................................................
Building/ Institution Name ....................................................................................................................
Flat/Room No. .......................................................................................................................................
Street Name ...........................................................................................................................................
Locality / Suburb ...................................................................................................................................
City / District .........................................................................................................................................
State .................................................................... Pin-code ...............................................................
Residence STD Code ......................................... Phone no. ..............................................................
Clinic/Hospital STD Code ................................. Phone no. ..............................................................
Fax No. ............................. Mobile No. ................................. Pager No. ..............................................
E-mail ....................................................................................................................................................
Food Preference [ ] Vegetarian [ ] Non vegetarian CME : Yes / No
IAP Delegate Fees Rs. .....................................................
Non-IAP Delegate Fees Rs. .....................................................
PG Student Fees Rs. .....................................................
Accompanying person Rs. .....................................................
Others Rs. .....................................................
Demand Draft Number............................................. of .......................................... Bank
.......................................... Branch dated ...............................
Please Note: Signature
* CME is free, however, prior registration is a must.
* Please send your payment only by demand draft. Please do not send any cash by post. Please do
not use cheque for payment. Demand draft to be made in favour of Pedicon 2004, payable at
Chennai.
* Please mail the registration form along with the Demand Draft by registered post or by courier only
to the following address.
Secretariat:
Dr. A.Balachandran, Organizing Secretary, PEDICON 2004,
IAP-TNSC Flat, Ground Floor, F Block, Halls Towers, 56 (Old No.33) Halls Road, Egmore,
Chennai-600 008. Tamilnadu, India.
Phone: 28190032, 28191524, 52145280 Email: pedicon2004@yahoo.com Web: www.pedicon 2004.com

96
 2003;5(4)367

INDIAN JOURNAL OF PRACTICAL PEDIATRICS

ADVERTISEMENT TARIFF
Official Journal of the Indian Academy of Pediatric - A quarterly medical journal
committed to practical pediatric problems and management update

Name ...................................................... FULL PAGE

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MANAGING EDITOR
Indian Journal of Practical Pediatrics
IAP-TNSC Flat, Ground Floor,
F Block, Halls Towers,
56 (Old No.33), Halls Road,
Egmore, Chennai - 600 008. India
Phone : 2819 0032
Email : ijpp_iap@rediffmail.com

97
Indian Journal of Practical Pediatrics 2003;5(4)368

Indian Journal of
Practical Pediatrics IJPP
Subscription Journal of the
Indian Academy of Pediatrics

JOURNAL COMMITTEE NATIONAL ADVISORY BOARD

Editor-in-Chief President, IAP

Dr. A.Balachandran Dr. H.P.S.Sachdev
Executive Editor
Dr. D.Vijayasekaran
Managing Editor President Elect, IAP
Dr. K.Nedunchelian Dr.M.K.C.Nair
Associate Editors
Dr. N.C.Gowrishankar
Dr. Malathi Sathiyasekaran Editor, Indian Pediatrics
Dr. P.Ramachandran
Dr. Panna Choudhury
Dr. C.V.Ravisekar
Dr. S.Thangavelu
Executive Members Members
Dr. B.Anbumani Dr. Ashok K.Rai
Dr. Janani Shankar
Dr. C.M.Chhajer
Dr. P.S.Muralidharan
Dr. K.Nagaraju Dr. S.R.Keshava Murthy
Dr. T.L.Ratnakumari Dr. Krishan Chugh
Dr. T. Ravikumar
Dr. B.R.Nammalwar
Dr. S.Shanthi
Dr. So.Shivbalan Dr. A.Parthasarathy
Dr. V.Sripathi Dr. M.Vijayakumar
Dr. Nitin K.Shah
Dr. Vijay N.Yewale
(Ex-officio)
 2003;5(4)369

Indian Academy
of Pediatrics
Kailash Darshan,
Kennedy Bridge,
IAP Team - 2003 Mumbai - 400 007.

President Members of the Executive Board

Dr. H.P.S. Sachdev Dr. C.M.Aboobacker (Kerala)
Dr. Apurba Kumar Ghosh (West Bengal)
Dr. Ashok Gupta (Rajasthan)
President Elect Dr. Ashok Kumar Gupta (Jammu & Kashmir)
Dr. M.K.C.Nair Dr. Ashok K.Rai (Uttar Pradesh)
Dr. Baldev S.Prajapati (Gujarat)
Dr C.P.Bansal (Madhya Pradesh)
Imm. Past President Dr. C.M. Chhajer (Tripura)
Dr. Dilip K.Mukherjee Dr. M.Dasaradha Rami Reddy (Andhra Pradesh)
Dr. K.W.Deoras (Chhattisgarh)
Dr. D.Gunasingh (Tamil Nadu)
Vice President Dr. S.R.Keshava Murthy (Karnataka)
Dr. C.P.Bansal Dr. Krishan Chugh (Delhi)
Dr. Mahesh Kumar Goel (Uttar Pradesh )
Dr. Manoranjan Sahay (Jharkhand)
Secretary General
Dr. Niranjan Mohanty (Orissa)
Dr. Nitin K. Shah Dr. Padmanabha Gandhi (Andhra Pradesh)
Dr. P.S.Patil (Maharashtra)
Treasurer Dr. K.R.Ravindran (Tamil Nadu)
Dr. Ramesh K.Yelsangikar (Karnataka)
Dr. Bharat R. Agarwal Dr. Sailesh G.Gupta (Maharashtra)
Dr. Satish V.Pandya (Gujarat)
Editor-in-Chief, IP Dr. (Mrs). Shabina Ahmed (Assam)
Dr.Shahshi B.P.Singh (Bihar)
Dr. Panna Choudhury Dr. S.C.Singhal (Haryana)
Dr. B.K.Sudhindra (Kerala)
Editor-in-Chief, IJPP Dr. Sudesh K.Sharma (Punjab)
Dr. Sunil Gomber (Delhi)
Dr. A. Balachandran
Dr. Tapan Kumar Ghosh (West Bengal)
Dr. Vijay N.Yewale (Maharashtra)
Joint Secretary Dr. R.Virudhagiri (Tamil Nadu)
Dr. D.Vijayasekaran Dr. Yashwant Patil (Maharashtra)