Clinical Profile of Culture-Proven Tuberculosis Cases Among Filipino

Children Aged 3 Months to 18 Years

Cherry Lyn P. Pama, M.D.* and Salvacion R. Gatchalian, M.D.**

(*Fellow and **Consultant, Infectious Diseases Section, Department of Pediatrics, University of the Philippines-
Philippine General Hospital, Taft Avenue, Manila)

ABSTRACT

The gold standard for confirming the diagnosis of childhood tuberculosis (TB) is the isolation of
Mycobacterium tuberculosis by culture. The diagnosis in most cases is still based on clinical evidence alone. A
descriptive study at the University of the Philippines-Philippine General Hospital and Research Institute for Tropical
Medicine was conducted to determine the presentation of tuberculosis in children with culture-confirmed tuberculosis.
Sixty-seven children aged 18 years old and below with culture-confirmed tuberculosis seen at Philippine
General Hospital (PGH) and Research Institute for Tropical Medicine (RITM) from June 1988 to May 2001 were
studied. The demographic data and clinical presentation were analyzed using the Epi-Info Version 6.
Younger subjects were observed having TB meningitis. Most children (57%) aged < 5 years old with history
of Bacillus Calmette-Guerin (BCG) immunization were found to have disseminated TB or TB meningitis.
Significantly, more children aged < 1 year old presented with seizures (p=0.029), sensorial changes (p=0.029) and
loose bowel movement (p=0.043). The presence of extra-pulmonary disease in all age groups was observed.
The physical examination findings indicative of generalized disease (lymphadenopathy, hepatomegaly,
splenomegaly) were common (73%) and tended to occur in younger children (median age, 4.0). The association
between anergy to purified protein derivative (PPD) test and severe TB was not observed.
Twenty two percent of the subjects and 14% of those with pulmonary disease had no significant findings on
chest x-ray. Atelectasis and miliary infiltrates, usually seen in children aged < 2 years old, were observed in older
children (mean age, 9.0) and pleural effusion, which is uncommon in infants and children was seen in nine very young
children (mean age, 1.0)
This study supports the use of history and clinical features to diagnose childhood TB. The clinical and
laboratory characteristics were consistent with those seen in previous series. (Phil J Microbiol Infect Dis 2001;
30(4);133-143)

INTRODUCTION

Tuberculosis (TB) has remained to be one of the most common causes of death among
Filipinos. According to the Department of Health, Philippine Health Statistics, from 1995 to
1997, TB was the fifth cause of mortality.1 In 1999, the Philippines ranked second in the western
pacific region and seventh worldwide in TB incidence and is one of the 23 countries with a high
burden of TB under World Health Organization (WHO) watch list.2 The dramatic increase in the
total number of cases of TB infection and disease in children is alarming.
The clinical presentation of TB in children takes many forms. The diagnosis in most
cases is still based on clinical evidence alone.3 The sensitivity of diagnostic techniques, including
acid-fast smear and culture, is low. Only 32 to 40% of gastric aspirates from children with
pulmonary TB are culture positive. Only 5 to 13% are acid-fast bacterium (AFB) smear positive.
The sensitivity of polymerase chain reaction (PCR) is comparable to culture for detecting
Mycobacterium tuberculosis in children. However, because of the limitation in specificity, the
results of PCR alone are insufficient to diagnose TB in children.4
The key to the diagnosis of TB in children is the clinical presentation but the isolation of
M. tuberculosis by culture still remains to be the gold standard for confirming the diagnosis.
Studies of childhood TB showed that only 40 to 50% of cases are culture proven.
There has been no published local study yet on culture proven TB in the pediatric age
group since most of the culture and sensitivity studies on M. tuberculosis have been done on the
adult population. The aim of the study is to describe the presentation of TB in children with
culture confirmed TB. Specifically, it aims to describe the clinical and laboratory characteristics
of these patients and to determine any association between variables and the positive TB culture
result.

MATERIALS AND METHODS

Children 18 years old and below with culture-confirmed tuberculosis seen at the
Philippine General Hospital and Research Institute for Tropical Medicine from June 1988 to
December 2000 (Retrospective Analysis), and January 2000 to May 2001 (Prospective Analysis)
were included in the study.

Demographic, medical and laboratory data were ascertained by chart reviews, for both
identified retrospectively and those identified prospectively. Associated illnesses were assessed
by chart review and included those listed in the admission data as well as those diagnosed during
the hospital stay. Physical examination findings were based on review of patient charts. TB cases
were classified as pulmonary and/or extra-pulmonary. Chest radiographic findings were based on
radiology reports. Data were entered into a questionnaire developed using Epi-Info Version 6.

Relevant information including acid-fast smear results, culture site, drug susceptibility
and dates of isolation was obtained from microbiology laboratory records. Drug resistance was
defined as resistance to any single drug or multiple drugs. Multi-drug resistance (MDR) was
defined as resistance to isoniazid and rifampicin with or without resistance to other drugs.

Tests of association using median test, chi-square test and Fisher’s exact test were used,
where appropriate.

RESULTS

Eighty-one (5.9%) children suspected to have TB were TB culture positive. Only sixty-
seven charts were retrieved for review.

Demographic Profile

Twenty-two (33%) were 1 to 5 years old; 15 (22%) were 11 to 15 years old; 11 (16.5%)
were less than 1 year old and 10 (15%) were 16 to 18 years old. Mean age was 6 years and the
mode was 15 years Majority of pediatric TB occurred in children < 5 years of age. There were
more males than females (37 (55.2%) vs. 30 (44.8%). Most of the subjects (74.6%) came from
Metro Manila. Boys were younger than girls (4 yrs vs. 6 yrs, median age) but this difference was
not found to be significant (p=0.717, median test) (Table 1).

Final Diagnoses

The most common diagnoses were pulmonary TB (40.3%), disseminated TB (32.8%),

TB meningitis (11.9%) and pneumonia (4.5%). Other less common diagnoses include, among
others, empyema thoracis, abscess and TB adenitis (Table 2).
There were no significant associations between age and pulmonary TB and disseminated
TB. However, age was significantly associated with TB meningitis, with younger subjects (<5 yrs
old) associated with the disease (p=0.048, Fisher’s exact test).
Table 1. Demographic profile Table 2. Final diagnoses

N % Age distribution
Age (years) <1 11 16.5 N % Median age, Years
1-5 22 33.0 Pulmonary TB 27 40.3 13.0 0.5-18.0
6-10 9 13.5 Disseminated TB 22 32.8 3.5 0.3-17
11-15 15 22.0 TB meningitis 8 11.9 1.4 0.8-9.0
16+ 10 15.0 Pneumonia 3 4.5 0.4 0.4-4.0
Median = 6; Others 7 10.4 6.0 0.5-16.0
Mode =15
Sex Male 37 55.2
Female 30 44.8
Place of Metro Manila 50 74.6
residence Cavite 4 6.0
Laguna 11 16.4
Batangas 1 1.5
Camarines Norte 1 1.5

Associated Illnesses

In addition to the primary illness, about 2/3 (43, 70%) of the subjects had an associated
illness. Malnutrition was present in more than half of the subjects (52.3%). Pneumonia with
malnutrition was present in 18 (26.9%) subjects while 17 (25.4%) had malnutrition only. Five
(7.4%) had an associated pneumonia only (Table 3). One patient had chronic renal failure
secondary to membranous proliferative glomerulonephritis (MPGN) who was on steroid therapy.
Other associated illnesses were anemia (5, 7.4%), staphylococcal pneumonia (3, 4.4%)
and intestinal parasitism (3, 4.4%). There were significantly more malnourished children with
disseminated TB than with other diagnoses (p=0.02).

BCG Immunization Status

Most children (56.7%) had history of BCG immunization while a fourth (25.4%) did not
receive BCG. In almost 18%, it was not known whether BCG was given or not (Table 4).
Immunization with BCG was not found to be significantly associated with pulmonary TB,
disseminated TB or TB meningitis.

Infectious Contact

A history of exposure to TB was elicited in 38 (45.7%) patients while 29 (43.3%) denied

history of exposure to TB.
Among the exposed group, the most frequently mentioned infectious contact was either
grandparent (39.5%), followed by either parent (34.2%) or either uncle or aunt (13.2%). Other
index cases mentioned were, a neighbor, a sibling, both grandparents, and simultaneously either
parent and sibling.
Majority (47.4%) of the infectious contacts were inadequately treated; only 18.4% were
treated and 15.8% were not treated at all. Treatment status was not known in 18.4% of the
infectious contact. Treatment status of the infectious contact was not significantly associated with
the diagnoses of pulmonary TB, disseminated TB and TB meningitis (Table 5).
Table 3. Associated illness Table 4. BCG immunization status

Malnutrition and pneumonia 26.9 Age distribution

Malnutrition only 25.4 N % Median age, Years
Pneumonia only 7.4 Given 38 56.7 4.0 0.2-18.0
Others 32.8 None 17 25.4 13.0 1.5-18.0
None 26.9 No data 12 17.9 2.1 0.4-16.0

Table 5. Percentage of treatment status of contact

Adequately treated 18.4

Inadequately treated 47.4
Not treated 15.8
Not known 18.4

Presenting Symptoms

The duration of onset of symptoms prior to admission/consult ranged from 0.1 to 144
weeks (1 day to 3 years, mean of 20 weeks, median of 4 weeks).
The most frequently seen symptoms were fever in 89.6%; cough in 76.1%; weight loss in
50.7%; anorexia in 44.8% and difficulty or breathing in 28.4%. Other more common symptoms
were malaise, vomiting, abdominal pain, seizure, increased sleeping time, hemoptysis, and night
sweats (Table 6).
There were significantly older subjects (> 1 year) who presented with hemoptysis
(p=0.001), easy fatigability (p=0.001), chest pain (p=0.008), joint pain (p=0.014), low back pain
(p=0.014), paresthesia from hip down (p=0.047) and orthopnea (p=0.047). On the other hand,
there were significantly younger subjects (<1 year old) who presented with seizures (p=0.029),
sensorial changes or increased sleeping time (p=0.029) and loose bowel movement (p=0.043).

Clinical Presentation

It can be seen from Table 7 that 65.7% of subjects showed both pulmonary and extra-
pulmonary infections; 23.9% had pulmonary disease only while 8.9% had extra-pulmonary
disease only. The presence of extra-pulmonary disease was not found to be significantly
correlated with age (p=0.44). However, it was significantly associated with nutritional status.
There were more malnourished subjects who had extra-pulmonary (p=0.05).
The presence of palpable lymph nodes was the most frequent extra-pulmonary clinical
finding (55.2%), followed by symptoms referable to the gastrointestinal tract (26.9%), central
nervous system (17.9%), skeletal system (9.0%), soft tissue (4.5%), genitourinary (3.0%) and
cardiovascular system (1.5%) as seen in Table 8. Many children with infection had diseases in
multiple sites (23 of 51, 45%).

Physical Examination

On physical examination (PE), lymphadenopathy was found in 62.7% of subjects, mostly

in the cervical area (61.2%). Hepatomegaly was noted in 37.3%, splenomegaly in 3.0% (Table 9).
These PE findings indicative of generalized disease were common findings (73%) that tended to
occur in younger children (median age, 4.0). The most common auscultatory finding was crackles
(41.8%).

Table 6. Presenting symptoms

Age distribution
N % Median age, Years
Fever 60 89.6 4.0 0.2-18.0
Cough 51 76.1 4.0 0.2-18.0
Weight l.oss/failure to thrive 34 50.7 10.5 0.3-17.0
Anorexia 30 44.8 4.0 0.3-17.0
Difficulty of breathing 19 28.4 1.2 0.2-18.0
Easy fatigability 12 17.9 13.5 1.0-18.0
Malaise 11 16.4 15.0 1.0-17.0
Vomiting 11 16.4 4.0 0.8-17.0
Abdominal pain 9 13.4 10.0 2.0-17.0
Seizure 8 11.9 1.75 0.8-11.0
Increased sleeping time 8 11.9 1.65 0.8-11.0
Hemoptysis 8 11.9 15.5 6.0-18.0
Night sweats 7 10.4 15.0 1.0-18.0
Loose bowel movement 7 10.4 2.0 0.5-9.0

Table 7. Clinical presentation

Age distribution
N % Median age, Years
Pulmonary and extrapulmonary 44 65.7 5.0 0.3-18.0
Pulmonary alone 16 23.9 15.0 0.2-18.0
Extrapulmonary alone 7 10.4 4.0 4.0-17.0

Table 8. Sites of extra-pulmonary infection

Age distribution
N % Median age, Years
Lymph node 37 55.2 6.0 0.5-18.0
Gastrointestinal 18 25.9 8.3 0.3-17.0
Central nervous system 12 17.9 1.4 0.2-15.0
Skeletal 6 9.0 12.5 1.0-17.0
Soft tissue 3 4.5 13.0 6.0-15.0
Genitourinary 2 3.0 10.5 10.0-11.0
Cardiovascular 1 1.5 0.7 0.2-15.0

Mantoux Test

Fourteen or about 21% had negative results with purified protein derivative (PPD) testing
and the same number and percentage had positive (measurement of > 8 mm) results. In more than
half (58%) of the subjects, PPD testing was not done.
 Of the 14 subjects who tested positive for PPD, 4 or 28% had pulmonary TB while 8 or
57.1% had disseminated TB, both conditions accounting for 85.1% of the subjects who tested
positive. Of the 14 subjects who tested negative, 5 or 35.7% had pulmonary TB while 7 or 50%
had disseminated TB, both conditions accounting for 85.7% of subjects who tested negative.
No significant association was found between malnutrition and results of the PPD test
(p=0.42, Fisher’s exact test).

Table 9. Physical examination findings

Age distribution
N % Median age, Years
Lymphadenopathy 42 62.7 5.0 0.5-18.0
Cervical 41 61.2 4.0 0.5-18.0
Submandibular 4 6.0 7.5 3.0-16.0
Axillary 4 6.0 10.5 1.0-15.0
Inguinal 3 4.5 10.0 1.0-14.0
Supraclavicular 2 3.0 11.0 9.0-13.0
Hepatomegaly 25 37.3 2.6 0.3-17.0
Splenomegaly 2 3.0 6.5 1.0-12.0

Chest Radiograph Findings

Of the 67 children, chest radiograph data were available for 55. Majority had one or more
of the following findings: hazy densities (13, 23.6%); cystic lucencies (12, 21.8%); consolidation
(11, 20.0%); pleural effusion (9, 16.4%), cavitations (6, 11.0%); miliary infiltrates (5, 9.0%);
nodular densities (5, 9.0%); atelectasis (4, 7.3%) and opacification (4, 7.3%). There was no
significant chest finding in 21.8% of the patients (Table 10). Fourteen percent (7/49) of patients
with pulmonary disease had normal chest radiograph findings.
Age was significantly correlated with some radiographic findings. There were
significantly more subjects aged less than 5 years old with pleural effusion (p=0.013) and nodular
densities (p=0.05). On the other hand, there were significantly more subjects > 5 years old who
showed cavitations (p=0.024).

Laboratory Findings

AFB smear was positive in 62.7% of culture-positive subjects. Common sources of smear
were gastric aspirate (44.8%) and sputum (38.8%). Other less common sources/sites were pleural
fluid, endothracheal aspirate, wound, stool, urine and lymph node biopsy (Table 11). The yield
from gastric aspirate was 60% while the yield from sputum was 73%. Older age (> 5 years) was
significantly associated with a positive AFB (p=0.024).

Drug Resistance

The susceptibility patterns were as follows: 49% resistant, 49% sensitive and 2% multi-
drug resistant strains. Twenty seven percent of the subjects showed resistance to at least one anti-
TB drug; 19.6% to 2 drugs and 2% each showed resistance to 3 and 4 drugs (Table 12).
Table 13 shows the number and percentage of subjects resistant to specific drugs. Almost
28% showed resistance to pyrazinamide (PZA), 27.4% to ethambutol (EMB), 15.7% to isoniazid
(INH), 8.2% to streptomycin (SM) and 2% to rifampicin (RIF). More than 22% were resistant to
ciprofloxacin (CIP), 5.5% to amikacin (AN), and 5.5% to kanamycin (K). Age was not
significantly associated with resistance to any of the anti-TB drugs. A positive AFB smear was
also not significantly associated with resistance to any anti-TB drugs.

Table 10. Chest radiograph findings

Age distribution
N % Median age, Years
Hazy densities 13 23.6 1.2 0.5-18.0
Cystic lucencies 12 21.8 3.5 0.6-17.0
No significant findings 12 21.8 2.1 0.2-15.0
Consolidation 11 20.0 3.0 0.2-15.0
Pleural effusion 9 16.4 1.0 0.3-9.0
Cavitation 6 11.0 14.5 6.0-17.0
Miliary infiltrate 5 9.0 9.0 3.0-14.0
Nodular densities 5 9.0 3.0 1.3-17.0
Opacification 4 7.3 9.0 1.0-15.0
Atelectasis 4 7.3 12.0 0.3-15.0
Mediastinal lymphadenopathy 3 5.4 15.0 9.0-15.0
Reticulonodular densities 3 5.4 15.0 1.0-16.0

Table 11. Laboratory findings

N %
Positive AFB smear 42 62.7
+1 22 32.8
+2 3 4.5
+3 8 11.9
+4 9 16.4
Culture sources N % N positive % yield
Gastric aspirate 30 44.8 18 60.0
Sputum 26 38.8 19 76.0
Pleural fluid 3 4.5 1 33.3
Wound 3 4.5 1 33.3
Endotracheal aspirate 2 3.0 1 50.0
Stool 1 1.5 1 100.0
Urine 1 1.5 0 0
Lymph node biopsy 1 1.5 0 0

Outcome

Forty six percent (46%) were hospitalized for more than 10 days; 41.8% for 1-10 days
and 11.9% were seen on outpatient basis. Median number of days hospitalized was 10 days with a
range of 0-108 days. Resistance to any one drug was not significantly associated with duration of
hospital stay (p=0.65).
Seven or 10.4% were deemed cured of the disease, 38.8% were improved and 13.4%
expired. About 1/3 or 37.3% of the subjects were lost to follow-up so outcome could not be
ascertained (Table 14). Outcome was not found to be significantly associated with nutritional
state nor with age.
Of the nine subjects who died, 4 died from complications of tuberculosis, 2 died
from adult respiratory distress syndrome (ARDS), 2 from pneumonia, and 1 from nosocomial
sepsis (Table 15). Six children manifested pulmonary disease, and 5 also had extra-pulmonary
infection. Six were infected with drug-resistant strain whereas 1 child was infected with a drug-
sensitive strain. Drug sensitivity testing was not done in two patients. The cause of death was not
significantly associated with age or with resistance to any anti-TB drugs.

Table 12. M. tuberculosis resistance pattern Table 13. Total drug resistance to anti-tuberculous drugs

N % Total N %
One drug 14 27.4 Pyrazinamide (PZA) 29 8 27.6
Two drugs 10 19.6 Ethambutol (EMB) 51 14 27.4
Three drugs 1 2.0 Isoniazid (INH) 51 8 15.7
Four drugs 1 2.0 Rifampicin (RIF) 51 1 2.0
Multiple drugs 1 2.0 Streptomycin (SM) 51 4 8.2
Ciprofloxacin (CIP) 18 4 22.2
Amikacin (AN) 18 1 5.5
Kanamycin (K) 18 1 5.5

Table 14. Outcome of treatment (%) Table 15. Causes of death (%)

Cured 10.4 Complications of tuberculosis 44.4

Improved 38.8 Adult respiratory syndrome 22.2
Died 13.4 Pneumonia 22.2
Lost to follow up 37.3 Nosocomial sepsis 11.1

DISCUSSION

There is clear evidence that the worldwide incidence of tuberculosis is increasing in

children and adults.5 The World Health Organization estimates 90 million cases worldwide and
30 million deaths, including 4.5 million children in the 1990s.6
In the Philippines, a prevalence survey taken in 1997 showed a nationwide prevalence of
63.4%, a rate essentially unchanged since the 1981-1983 survey. Males had a higher prevalence
than females (67% vs. 60.3%). The highest prevalence rate was shown by individuals in the age
group 40-49 years (86.3%).7 In general, older age groups had higher prevalence than younger age
groups.
Tuberculosis in children is a sentinel indicator of the continuing transmission of the
disease in a community, hence, is a measure of the success of public health measures to control
the disease. Sustained transmission with subsequent infection at an early age establishes an
important reservoir of future cases that can present over a period of decades. In the Philippines,
the prevalence rate among children 5-9 years was found to be 16.1, again, essentially unchanged
from the 1981-83 prevalence rate for the age group, despite increases in BCG coverage over the
years.8 An evaluation of control strategies seems to be needed.
The present study found a higher proportion of culture-positive cases among children 1-5
years old (33%), followed by the adolescent age group from 11-15 years old (22%). We also
found a high proportion (16.5%) of infants less than one year of age with tuberculosis. This
suggests a continuing transmission of the disease to the young from adults infected with the
disease resulting in primary TB for groups 1-5 years old and less than 1 year old. For the
adolescent group of children 11-15 years old, their disease could possibly be post primary
tuberculosis.
More than 40% of the subjects of this study had pulmonary TB. Disseminated TB was
present in 32.8% and TB meningitis was diagnosed in 11.9%. The distribution of pulmonary and
disseminated TB in this study was not age-related. However, there were significantly more
subjects in the younger age group (<5 years old) who had TB meningitis. The state of
malnutrition was found to be a factor for the occurrence of disseminated TB in children (but not
for pulmonary TB and TB meningitis). More than half of the subjects in the study (52.3%) were
found to be malnourished. Previous research has clearly shown how malnutrition adversely
affects the host’s defense mechanism, by suppressing cell-mediated response to infection.8 In
malnourished children, there is higher risk of a localized lesion to become progressive or
generalized disseminated TB, because of poor immune response to infection.
More than half (56.7%) of the subjects received BCG. BCG vaccine is routinely given in
almost every country.1 A meta-analysis of 14 prospective BCG trials and 12 case-control studies
concluded that the average protective effect of BCG vaccines is 50%.11 Protection is higher for
meningitis and disseminated disease than for pulmonary tuberculosis. It is not clear to what extent
strain variation among BCG vaccines, timing and schedule of administration affect the vaccine’s
efficacy.10 In the present study, BCG immunization was not significantly associated with
disseminated TB, nor with TB meningitis. However, there was a significantly higher proportion
of vaccinated children under 5 years age group, as compared to those in over 5 year age group,
among cases of disseminated TB and TB meningitis. The results, therefore, may indicate that
there is still a significant chance of developing complicated TB even in the presence of BCG
vaccination. This supports the previous studies that showed a probable effectiveness of BCG
against TB meningitis only for a limited duration of time.12,13
In 56.7% of the subjects, a history of exposure to TB from immediate family
(grandparents, parents, aunt/uncle and siblings) was elicited. Transmission of TB was possible
because of inadequate or non-treatment of the infectious adult. Drug-resistance in children can
also be traced to transmission of these drug-resistant strains from the infected adult to the child.
Tuberculosis in children is hard to diagnose. Usually, finding an index case leads to
family contacts and screening for TB becomes important. Most children already infected may not
show any signs and symptoms at all, even with significant abnormalities in the chest radiograph.3
Several studies showed that cough, fever, loss of appetite, rales, diarrhea/vomiting, decreased
breath sounds, weight loss and seizures are the most common symptoms in children with
TB.14,15,16,17 In this study, we also found these signs and symptoms to be most common. Some
signs and symptoms such as hemoptysis, easy fatigability, orthopnea, among others, were
significantly associated with older children while seizure, change in sensorium and loose bowel
movement were significantly more common in younger children.
This group of children differed from previous series in that many had physical findings
suggestive of generalized disease including lymphadenopathy, hepatomegaly and splenomegaly.17
The most common pulmonary findings were the presence of crackles in more than 40% and
decreased breath sounds in about 18% of subjects. The bronchi of children are of smaller caliber
than adults and more easily compressed by enlarging hilar lymph nodes. As the hilar lymph nodes
enlarge, bronchial obstruction may occur and signs of air trapping such as wheezing and
decreased breath sounds may occur. The most common extra-pulmonary finding is cervical
lymphadenopathy, occurring in 61.2% of cases. This is consistent with the findings of large
studies, which reported 50-70% of cases of childhood TB had cervical lymphadenopathy.18,19
Twenty-eight subjects were tested with PPD, and only 14 or 50% of the culture-positive
subjects showed positive results with the test. Problems with tuberculin testing have been
recognized, such as false positivity with other mycobacterial infections, and the problem of
booster phenomenon in previously infected individuals.5 More importantly, false negative results
can be as high as 50%,20 which could explain the 50% rate of negative results obtained in this
study. The association between anergy to PPD and severe TB has been well-documented15 but
this was not observed in this group of children.
Chest x-rays may or may not show significant findings. In this study, 21.8% of the
subjects and 14% of those with pulmonary disease had no significant findings on chest x-ray. The
radiological “hallmark” of primary tuberculosis is mediastinal or hilar lymphadenopathy. The
most frequently involved nodes are the hilar and right paratracheal, and are usually unilateral or
right-sided.21-22 In our study, mediastinal lymphadenopathy was present in only 3 or 5.4% of
subjects. Primary TB, on chest x-ray can also be indicated with the presence of parenchymal
infiltrates, frequently in the form of homogeneous infiltrates with ill-defined borders. In our
study, hazy densities were found in 20% of cases, but no distinction was made as to their
homogeneity or heterogeneity to be able to help distinguish their underlying etiology (whether
due to primary or post primary TB). Lobar or segmental atelectasis occurs most frequently in
children under 2 years of age. The atelectasis is caused by either endobronchial disease or
external bronchial compression due to hilar adenopathy. Pleural effusion is uncommon in infants
and young children.22 Miliary disease is frequently seen in children less than 2 years of age.22 In
contrast, atelectasis and miliary disease were found in older children and pleural effusion in
younger children in this study.
The radiologic patterns observed in post-primary TB include parenchymal disease and
cavitations, airway disease, pleural disease and others. The first manifestation of parenchymal
disease is a heterogeneous poorly defined infiltrate within the apical/posterior segments of the
upper lobe or the superior segment of the lower lobe. This may progress to lobar or lung
opacifications or may evolve into better-defined coarse reticular or nodular opacities. Cavitation
may occur (present in 9% of our subjects). The cavities are often multiple and between 1-3 mm.
They have thick and irregular walls and can become emphysematous. Pleural effusions in post-
primary TB are often small (as opposed to the large effusions characteristic of primary TB) and
associated with significant parenchymal disease.21 The radiological findings in our study are
insufficient to distinguish between primary and post-primary disease, although the small
proportion of subjects with mediastinal lymphadenopathy and the presence of a number of cases
with cavitation, reticulonodular densities, opacification and atelectasis suggest a preponderance of
postprimary cases.
The diagnosis of TB in children is also rendered difficult because of poor yield in
laboratory tests, in addition to the lack of characteristic symptoms, as compared with adults.
Conventional diagnostic tests, including the acid-fast stain and mycobacterial culture, are
frequently negative in children with TB because of lower mycobacterial colony counts and poor
tussive force. Even under the best conditions, the yield from gastric aspirates in children is
commonly less than 50%.3 In our study, the yield from gastric aspirate was 18/30 or 60%, and
from sputum, it was 19/26 or 73%. These are relatively high figures compared with those in the
literature.4,23,24 A culture should always be requested concomitantly with AFB smear because a
negative smear does not rule out active TB and not all positive AFB smears are M. tuberculosis.25
Drug resistance to M. tuberculosis occurs because the patient fails to adhere to effective
therapy or because the physician prescribes an inadequate treatment regimen. In many developing
countries, 20% to 30% of M. tuberculosis isolates are resistant to at least one first-line anti-TB
drug. MDR statistics is scarce. In New York, USA, considered as high risk for TB due to the
large immigrant population, overcrowding and poverty, MDR was only 1% of the total cases.26 In
South Africa, the figure for MDR was 1.1%.26 In our study, we found that nearly 30% of subjects
were resistant to at least one anti-TB drug and 23.6% to 2 or more drugs. Two percent of the
cases were MDR. There are two major types of resistance. Primary resistance occurs when a
person is infected with M. tuberculosis already resistant to a drug. Patterns of primary drug
resistance among children tend to mirror those found in adults in the same population.27,28,29
Secondary resistance occurs when drug-resistant organisms emerge as the dominant organism
during therapy. The major causes of secondary drug resistance are poor compliance by the patient
or poor management by the physician. Noncompliance with one drug is more likely to lead to
secondary resistance than failure to take all drugs. In our study, resistance to INH and rifampicin
is lower than those of ethambutol and PZA. INH and rifampicin, in combination, are frequently
given to children, and emergence of resistance to these drugs among our subjects may represent
secondary resistance. Resistance to pyrazinamide, ethambutol, and streptomycin among children
in this study may represent primary resistance as these are usually given to adults under
quadruple therapy. The figure of drug resistance presented in this study is disturbing and implies
the need for sensitivity studies even for primary cases of tuberculosis in children. The clinical
features were similar in children with drug susceptible-and drug resistant TB.
Mean duration of hospitalization was 10 days. Prolonged hospitalization >10 days, could
be due to associated illness such as pneumonia as well as to a severe primary diagnosis such as
disseminated TB or TB meningitis. Resistance to any one drug was not associated with duration
of hospitalization. Follow-up of cases showed that 10.4% were deemed cured of the disease,
38.8% improved while 13.4% expired. More than 1/3 of the subjects were lost to follow-up thus
outcome could not be ascertained. Outcome of treatment was not found to be significantly
associated with nutritional state or with age.
Four patients died from complications of tuberculosis (overwhelming TB, brainstem
failure secondary to TB meningitis) and five died from associated illnesses such as ARDS with
septic shock, pneumonia and nosocomial sepsis. Three of the mortalities were less than 1 year
old; 2 were less than 5 years old and four were from 6-15 years old. The cause of death was not
significantly associated with age or with resistance to any anti-TB drugs.

CONCLUSION

With difficulty in confirming childhood TB by culture, this study supports the use of
history and clinical features to diagnose TB in children.
Early case finding and adequate treatment is necessary to prevent excess mortality and
morbidity among children and to prevent future disabilities brought about by inadequate or non-
treatment. A contact investigation of the household should be initiated immediately when a child
is suspected of having TB to establish the diagnosis and guide therapy. An evaluation of the
public health strategies to control the disease should be done as childhood TB signifies recent and
ongoing transmission in the community.

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