INTRAUTERINE & PERINATAL INFECTIONS

Dr Maria Kahar Bador

Lecturer
Department of Medical Microbiology
MBChb.BaO(UK), Mc Med Micro (Lond) Dip L!"M (Lond)
OU"L#$%
&. Definition
B. Pathophysiology
C. Aetiological agents
D. General clinical features
%. Specific agents -
1. Clinical Features
2. Diagnosis
3. Treatment
. Pre!ention
&. Definition
"eonatal inf # appearing $ithin first $%s of &irth
''''''''''''l''''''''''''
Congenital Postnatal
'''''''''''''''''''''''''''
(ntrauterine Perinatal
l
)Transplacental* )Ascen+ing At +eli!ery*
B. 'athophy(iology
Foetus protecte+ &y,
-aternal immunity )e.g. passi!e transfer of (gG*
Foetal mem&ranes
Foetus at ris%,
(mmature immune system
.rganogenesis )+epen+s on gestational age*
/igh micro&e loa+
C.&etiological agent()
Congenital Infections
"O*C!

" o+opla(mo(i(
O ther() ,aricella, B-., Li(teria,yphili( ,/onorrhoea,
* ubella
C ytomegalo0iru(
! erpe(,!epatiti( B ,C, !#,
Perinatal infections
-. e+ually)tran(mitted
Neisseria gonorrhoeae
Chlamydia trachomatis
/uman papilloma!irus
/erpes simple0 !irus
/(1 )also &loo+-&orne*
/epatitis 2 3 C4 )also &loo+-&orne*
)4 not se0ually-transmitte+*
1. 2$ormal3 maternal flora
Group 2 streptococcus )Strep. agalactiae*
5ntero&acteria6 e.g. E. coli
D. /eneral Clinical 4eature(
Common to "O*C! infections
4 lo$ &irth$eight
4 preterm +eli!ery
4 anaemia6 throm&ocytopaenia
4 hepatitis $ith 7aun+ice an+ hepatosplenomegaly
4 sei8ures
4 microcephaly
4 mental han+icap
4 encephalitis
4 failure to thri!e
%. pecific agent(

Toxoplasma gondii
.rganism,
Proto8oa 6or+er 5ucocci+ia
CAT,
+efiniti!e host for repro
transmitte+ &y oocysts in the faeces
/9-A"S,
ac:uire+ &y
ingestion of contaminate+ cysts or meat6 lam& an+ por%
)in*+irect contact $ith cat faeces )sporocyst *
transfer $ithin organ transplant
Pathology,
Tropho8oite
o&ligate intracellular parasite
reticuloen+othelial cells mainly
multiplies &inary fission6 cell +isruption an+ +eath
Clinical features
Gen , $i+e range
-ost asymptomatic.
mil+6 self-limiting6 non-specific (- syn+rome
Disseminate+ organ +amage &rain6 eyes6 muscles6 li!er6 an+ lungs
immunocompromise+ #se!ere 6 A(DS -focal neurological +efect space-occupying lesion
Cong
1;<
se!ere +amage at or shortly after &irth
neurological +amage
cere&ral calcification6
hy+rocephalus
chorioretinitis.
=; - >;<
months or years
&ilateral !isual loss +ue to chorioretinitis 6post u!eitis
hepatosplenomegaly
5pi+emiology of Congenital To0oplasmosis
pregnant mothers
primary infection 1 - ? per 1;;; in the 9@
fetal +amage ris% if infect earlier
!ertical transmission ris% less 33 <
symptomatic +isease 1 in 1;6;;;
increase+
/(1 infection
countries $here ra$ meat is eaten
Diagnosis - may &e +ifficult
-aternal (g-6 serocon!ersion (gG
Cor+ (g-A (gA
PCBA culture of amniotic flui+
Pre!ention
Antenatal screening in some countries
Treat infecte+ mother 3 &a&y $ith spiramycin or pyrimethamine-sulpha+ia8ine
Herpesviruses
5n!elope+ +ou&le stran+e+ D"A !iruses.
Three su&families,
# &lphaherpe(0iru(e( ) !,)-, !,)1, ,5,
# Betaherpe(0iru(e( ) CM,, !!,)6, !!,)7
# /ammaherpe(0iru(e( ) %B,, !!,)8
Features-
# Catent or persistent infection follo$ing primary infection
# Beacti!ation +uring immunosurpression
# more serious in immunocompromise+ patients.
o ,aricella 5o(ter ,iru(
/erpes!iruses
su&family alphaherpes!irus
+s D"A
en!elope+ !irus
Genome si8e
Serotype
1 antigenictype only some cross reaction $ith /S1
/en clinical feature(
Primary infection
!aricella )chic%enpo0*
Secon+ary
/erpes 8oster )shingles*
Pregnancy
Congenital herpes
"eonatal herpes
Transmission
Bespiratory +roplets6 !esicles contact
(ncu&ation perio+
1-21 +ays
(nfectious perio+
from +ays &efore the appearance of the rash until all lesions ha!e sca&&e+ o!er
)appro0imately one $ee%*.
Pregnancy
3 per 1;;; $omen ) 9@ *
(mmune-
>;< $omen ha!e anti&o+ies to !aricella 8oster !irus also protecte+ if secon+ary
occurs
"onimmune
potentially +angerous +isease
fetal 3maternal mor&i+ity high
fi!e times more li%ely to &e fatal than in non-pregnant $omen
1< +e!elop pulmonary in!ol!ement esp smo%ing
Fetal outcome
-ost healthy
(n utero
&reach -Congenital
Perinatal-"eonatal
Congenital A fetal !aricella syn+rome
Bare
$hen infection occurs early
Bis%
;.D< if 2-12 $ee%s preg
E 1.< if 12-2= $ee%s
;< if from 2= $ee%s on
;.>1< o!erall ris% first 2; $ee%s
Clin features
s%in lossAscarring
C"S impairment )e.g. hypotonia*
lim& hypoplasia Aparesis
C2F
microcephaly6
ophthalmological a&normalities.
"eonatal
Cate stages of pregnancy
cross the placenta
(mmunity
sufficient
if rash in mother occurs G1 $ee% &efore +eli!ery
(nsufficient
if mother ill D +ays &efore until = hrs after +eli!ery
Clin features
!ary from a mil+ +isease to a fatal +isseminate+ infection.
Pre!ention 3Treatment
For suscepti&le mother,
Ci!e attenuate+ !accine )&efore pregnancy*
1H immunoglo&ulin )after e0posure*
infection control precautions
For ne$&orn
1H immunoglo&ulin if mother gets c-po0 last I +ays of pregnancy or the first
1 +ays after +eli!ery.
infection control precautions
Treatment
(f acute acyclo!ir
Ca&oratory Diagnosis
Barely re:uire+ for primary characteristic clin features
1irus (solation
2-3 $ee%s for a results.
Serology
(gG past infection an+ immunity
(g- recent primary infection.
Direct +etection
5- !esicle flui+s cannot +istinguish /S1 an+ 1H1.
(F on s%in scrappings can +istinguish
PCB
Parvovirus !"
Properties
na%e+ icosahe+ral
ss D"A
Antigenically +istinct from the !iruses
foun+ in faeces6 BA-1 an+ other par!o!iruses
5pi+emiology3 Pathogenesis
21> present throughout the year
.ut&rea%s
in temperate climates out&rea%s more in the spring an+ summer
aroun+ primary schools ;< of pupils may &e infecte+.
Commonest amongst - 1; yr ol+s.
2y a+ulthoo+ ?;< population seropositi!e.
Transmission
Bespiratory sprea+ usual route
2loo+&orne occur
Clinical features
Pregnancy
not associate+ $ith increase+ ris% of fetal malformation
29T fetal loss
ma7ority of pregnancies procee+ to term $ith +eli!ery of normal infants
infection in first trimester D - 1;< fetal loss.
(nfection in secon+ trimester 12.D<.
/y+rops fetalis
seen in ne$&orn $ith secon+ an+ thir+ trimester infection
-aternal infection occurs 2 to 12 $ee%s prior to +iagnosis
Se!ere anaemia lea+s to heart failure6 effusions6 +iffuse oe+ema
J2; $ee%s gestation
Clinical features
5rythema infectiosum
Chronic haemolytic anaemias
Aplastic crisis
(mmunocompromise+
persistent infection in patients
Diagnosis
Differential +iagnosis
all +iseases of maculopapular rash eg. ru&ella6 entero!iruses6 ar&o!iruses6 streptococcal
infection6 allergy.
1irus Detection
+etection of the !irus in fetal &loo+ samples or autopsy material
+irect or immune 5-.
B(A or D"A-D"A hy&ri+i8ation6
PCB
Anti&o+y Detection
5C(SA or B(A. Kanti&o+y captureK
+etection of either )i* 21>-specific (g- or )ii* a rising titre of 21> specific (gG.
21> specific (g- may &e +etecte+ in such tests up to 3 months after the onset of
symptoms.
21> (gG lasts longer &ut this anti&o+y is not detectable lifelong follo$ing infection.
patients $ith no +etecta&le (gG may ha!e e0perience+ pre!ious 21> infection
Treatment
During pregnancy
Supporti!e only
pregnancy shoul+ &e allo$e+ to procee+ $ith monitoring.
At +eli!ery e0amination of the cor+ &loo+ for 21> (g-.
Chil+ follo$e+ up for +elaye+ se:uelae
(mmunocompromise+
persistent 21> infection
only specific treatment
a+ministration of /"(G
Pre!ention
(nfection control /"(G
Treatment
erythema infectiosum
rarely necessary6syptomatic
chronic haemolytic anaemias
transfusion of erythocytes until a satisfactory /& le!el
Pre!ention
(nf control
Lis#eria mono$%#ogenes
GPB6 L-haemolytic
-other infecte+ &y,
contact $ith animals6 soil
eating contaminate+ foo+ or unpasteurise+ mil%A soft cheese
-other
mil+6 flu-li%e illness
2acteraemia may cause,
a&ortion
premature la&our
neonatal sepsisA meningitis
Treatment, ampicillin EA- gentamicin
Ru&ella
Properties
"on-arthropo+-&orne toga!irus
Genus Bu&i!irus
only mem&er
5n!elope+ !irus6
?;nm in +iameter6
nucleocapsi+ 33nm
symmetry icosahe+ral &ut !irus particle has a pleomorphic appearance.
Genome
ssB"A E!e ;S
B"A consists of 3 structural proteinsM 51 52 mem&rane &oun+ glycoproteins6 an+ C capsi+ protein
51 has ? +istinct antigenic +eterminantsM associate+ $ith haemagglutination6 an+ 2 $ith
neutrali8ation
serotype
."5
Gro$th
in a $i+e range of cell lines. (t (
n+uces a CP5 only in continuous cell lines such as B@13 )ra&&it %i+ney* an+ 1ero
*ubella
%pidemiology
Forl+$i+e
2efore immunisation
.ut&rea%s ten+ to occur Spring an+ Summer.
uncommon in preschool chil+ren &ut out&rea%s (nfection in!ol!ing school chil+ren an+ young
a+ults $ere common.
D;< of 1; year ol+s ha!e ru&ella anti&o+ies.
=;< of $omen of chil+&earing age immune
Pro&lem upta%e
*ubella
Pathogenesis
(ncu&ation perio+
13 to 2; +ays
Transmission
&y respiratory route.
Beinfection
"atural infection high le!el of protection from reinfection.
can occur $hich is generally asymptomatic.
Beinfection in pregnancy minimal ris% to the fetus
Congenital infection
!irus enters fetus +uring maternal !iraemic phase through the placenta.
rapi+ +eath of some cells an+ persistent !iral infection in others
+amage to all germ layers
Chromosomal a&errations
re+uce+ cell +i!ision
1irus high if the mother infecte+ +uring first trimester. (mmune sytem immature
!irus persists throughout the gestation
can &e isolate+ from most organs6secretions.The mechanism of !irus persistence +efects in cell-
me+iate+ immunity
*ubella
Pathogenesis
First trimester
ris% of ma7or malformations 1;< to D<

ris% greatest first = $ee%s of pregnancy )/ansha$ et al 1>=D*
critical phase of organogenesis.
Car+iac an+ eye +efects are more li%ely
13 an+ 1? $ee%s
Deafness usually sole manifestation
1? to 2; $ee%s of gestation
retinopathy an+ hearing +efects
*ubella
Clinical Features
Bash
!iraemia occurs 3 !irus +isseminates throughout the &o+y.
(n chil+ren rash onset a&rupt.
(n a+ults pro+romal phase for a +ay or t$o rash +e!elops.
Typically maculopapular rash
first appears on face sprea+s to the trun% an+ lim&s.
J 3 +ays.
immunopathological mechanism
Cympha+enopathy a $ee% &efore rash an+ 2 $ee%s after the rash has gone
*ubella
Clinical Features
Noint in!ol!ement
is the commonest complication an+ occurs in up to ?;< of a+ult females.
The fingers6 $rists %nees an+ an%les are most fre:uently affecte+.
The arthralgia lasts usually 3- +ays.
Arthralgia is rare in males an+ prepu&ertal females. An
5ncephalitis
+e!elops in 1 A 1;;;; &ut the prognosis is goo+.
Trom&ocytopenic purpura
may present as purpuric rash6 epita0is6 haematuria an+ G( &lee+ing.
(n 2D< the infection is su&clinical..
*ubella
Clinical Features Congenital ru&ella syn+rome )CBS*
"ran(ient9)
(9GB6 throm&ocytopenic purpura6 hepatoslenomegaly an+ haemolytic anaemia.
first fe$ $ee%s of life
not permanent .
Transient &one lesions in 2;<
2D< ha!e a meningoencephalitis E-lea!e neurological se:uelae.
Naun+ice common
De0elopmental9)
Sensorineural +eafness6 mental retar+ation6 insulin-+epen+ent +ia&etes.
(DD- common manifestation of CBS ) up to 2;<*. Delaye+ onset a+olescence or a+ulthoo+.
Autoimmune mechanisms may &e in!ol!e+.
may ta%e months &efore &ecome apparent &ut persists permanently.
2et$een 3 - 12 months late onset +iseaseK.
some infants +e!elop a ru&&elliform rash6 persistent +iarrhoea an+ pneumonitis referre+ to as high
mortality.
'ermanent9)
/eart +efects )patent +uctus6 1SD6 pulmonary !al!e stenosis*6 eye +efects )retinopathy6 cataract6
microopthalmia6 glaucoma6 se!ere myopia*6 C"S +efects )microcephaly6 psychomotor retar+ation*.
*ubella
Clinical Features Congenital ru&ella syn+rome )CBS*
*ubella
La& +iagnosis
Difficult clinically
Serology
-ain +iagnosis of ru&ella infection.SB/6 5C(SA
A recent ru&ella infection can &e +iagnose+ &y
1* +etection of ru&ella-specific (g-6
)2* rising titres of anti&o+y in /A( an+ 5C(SA tests
)3* serocon!ersion
/istory
5ssential accurate information relating +ate an+ time of e0posure6 onset of illness.
A history of pre!ious ru&ella !accination Epre!ious results of ru&ella screening tests.
Pregnant $omen #&loo+ collectec asap
1irus isolation
Cess use+ no$
from nasopharyngeal secretions ) an+ occasionally from faeces an+ urine *
I +ays &efore an+ up to I +ays after rash.
*ubella
Diagnosis congenitally ac:uire+ ru&ella
Presence of ru&ella (g-
in cor+ &loo+
serum samples ta%en infancy
Detection of ru&ella anti&o+ies
at a time $hen maternal anti&o+ies shoul+ ha!e +isappeare+ )appro0.? months of age*
(solation of ru&ella !irus
from infecte+ infants in the first fe$ months of life
Prenatal +iagnosis
Amniotic flui+ fetoscopy (g-
*ubella
Treatment an+ Pre!ention
Treatment
Supporti!e 6 counselling in pregnancy
Pre!ention
1accination
Passi!e immunisation
/"(G
+oes not pre!ent infection in non-immune contacts
may re+uce the li%elihoo+ of clinical symptoms
may re+uce the le!el of maternal !iraemia an+ ris% to fetus.

Antenatal screening
(nfection control
C%#omegalovirus
Properties
/erpes!iruses
su&family &etaherpes!irus
+s D"A
en!elope+ !irus
Cytomegalo!irus
5pi+emiology
(nci+ence
De!elope+ countries
# higher stan+ar+ of hygiene6
# ;< of a+olescents are infecte+
# I;< of the population is infecte+
De!eloping countries
# >;< of people infecte+
Transmission
1ery succesful
1ertical an+ hori8ontal
2loo+ an+ pro+ucts
(n utero6 peri 3postnatal
Perinatal 1; times more common
2 - 1;< of infants are infecte+ &y the age of ? months $orl+$i+e
1-2< li!e &irths are infecte+M up to 1;< of these ha!e symptoms
;< foetal infection if maternal primary infection
Cytomegalo!irus
Pathogenesis
Cife long
Beacti!ation
# Perio+ically
# immunocompromise+ esp
# infectious !irions appear in the urine an+ the sali!a
# Bare lea+ing to !ertical transmission ;.1D - 1<.
Perinatal infection
# mainly through infecte+ genital secretions or &reast mil%.
Postnatal infection
# mainly occurs through sali!a.
# Se0ual transmission may occur as $ell as through
# &loo+ an+ &loo+ pro+ucts an+ transplante+ organ.
Cytomegalo!irus
Clinical
1; - 2;< are symptomatic at &irth
=; - >;< are asymptomatic at &irth &ut later e0hi&it,
mental han+icap
!isual impairment
progressi!e hearing loss
+elaye+ psychomotor retar+ation
intrauterine infection less li%ely to &e suspecte+
Congenital infection #
cytomegalic inclusion +isease
Perinatal infection
usually asymptomatic
Postnatal infection #
usually asymptomatic.
minority ifectious mononucleosis
(mmunocompromise+
A(DS 3 transplant recipients an+ A(DS
se!ere C-1 +isease
pneumonitis6 retinitis6 colitis6 an+ encephalopathy.
Beacti!ation or reinfection
usually asymptomatic e0cept in immunocompromise+ patients
Cytomegalo!irus
Cytomegalic (nclusion Disease
C"S a&normalities
microcephaly6 mental retar+ation6 spasticity6 epilepsy6 peri!entricular calcification.
5ye -
choroi+oretinitis an+ optic atrophy
5ar #
sensorineural +eafness
Ci!er -
hepatosplenomegaly an+ 7aun+ice
Cung #
pneumonitis
/eart #
myocar+itis
2loo+
Throm&ocytopenic purpura6 /aemolytic anaemia
Cate se:uelae
in in+i!i+uals asymptomatic at &irth
hearing +efects an+ re+uce+ intelligence.
Cytomegalo!irus
Ca&oratory Diagnosis
1irus (solation
gol+ stan+ar+ &ut up to $ee%s
rapi+ culture metho+s eg D5AFF test 2-= hours.
2a&y- from urine 1-3 $ee%s
Direct +etection
/istology C-1 inclusion anti&o+ies Apresence of C-1 antigens. Co$ sensiti!ity
pp?D C-1 antigenaemia test in immunocompromise+ patients.
PCB for C-1-D"A 6 interpretation pro&s
2a&y-urine 1-3 $ee%s
Serology
-um
(gG anti&o+y past infection.
(g- anti&o+y in+icati!e of primary infection
Also reacti!ation in immuno compromise+ patients
2a&y
2loo+ (g- in first 3 $ee%s of life
Cytomegalo!irus
Treatment 3Pre!ention
Treatment
Supporti!e only
unless immunocompromise+
ganciclo!ir6 forscarnet6 an+ ci+ofo!ir.
Congenital infections
9nless primary not usually possi&le to +etect
counselling
Peri an+ post natal - "ot nec

Pre!ention
no relia&le C-1 !accine a!aila&le.
&est &y re+ucing e0posure to to++lerOs urine
&loo+ for +onation to infants shoul+ &e from C-1-negati!e +onors.
%+po(ure of foetu( to infection: outcome(
Fhat +o $e +o to pre!ent foetal an+ neonatal infectionP
1accinate all potential mothers
Tetanus
Bu&ella
/epatitis 2
1H1 )in 9SA6 Napan
Antenatal screening of pregnant mothers
/(1
/epatitis 2 surface antigen
Syphilis
Bu&ella )not +one in -alaysia*
To0oplasma )selecte+ countries only6 e.g. France*
Group 2 streptococcus )selecte+ countries only6 e.g. 9SA*
Fhat +o $e +o to pre!ent foetal an+ neonatal infectionP
(n some infections in pregnant mothers6 there are inter!entions to re+uce ris% of foetalAneonatal
infection,
Maternal infection Maternal inter0ention
$eonatal prophylactic
inter0ention
/(1 Antiretro!iral +rugs6 caesarean6
no &reast-fee+ing
Antiretro!iral +rugs
/epatitis 2 Screening /ep status in high ris%
groups (1D9 6 en+emic
Acti!e immunisation EA-
immunoglo&ulin
1H1 (mmunoglo&ulin )if early
pregnancy*
(mmunoglo&ulin )if near +eli!ery*
/S1-1 3 2 Caesarean Aciclo!ir
Syphilis Penicillin Penicillin
To0oplasma Anti-To0oplasma +rugs Anti-To0oplasma +rugs
Group 2 strep Penicillin .&ser!e EA- penicillin
Than% you Q