Childhood Tuberculosis in Household Contacts of Newly

Diagnosed TB Patients
Srichand Batra1, Afsheen Ayaz2, Ali Murtaza1, Shakil Ahmad1, Rumina Hasan2*, Ruth Pfau1
1 Marie Adelaide Leprosy Center, Karachi, Pakistan, 2 Department of Pathology and Microbiology, Aga Khan University, Karachi, Pakistan

Abstract
Introduction: Childhood tuberculosis (TB), although estimated to account for a major proportion of the global TB disease
burden, has a lower public health priority. Reliable research and surveillance data on childhood TB is limited in most regions
of the world. This study was conducted to assess the burden of childhood TB among the household contacts of new TB
patients in Karachi, Pakistan.

Methods: A retrospective analysis of children (,15 years) who were household contacts of new adult TB patients
presenting to Marie Adelaide Leprosy Center (MALC) clinics in Karachi during the period of 2008 to 2010 was conducted.

Results: Of the household children contacts (n = 6613) screened, 317 were suspected and 121(1.8%) diagnosed with TB.
These included 89 (73.6%) with pulmonary and 32 (26.4%) with extra-pulmonary disease. Smear positivity rate in pulmonary
cases was 32.6%. Mean age of children diagnosed with TB was 11.7 (62.8) years. Within the child-contacts screened, disease
was found to be significantly higher among females (2.3%) in comparison to males (1.2%) (p-value ,0.01). The commonest
relationship of source cases to diagnosed children was the mother (n = 51, 42.1%). The source case was a female for 66.1%
(n = 76) of the children.

Conclusion: A smear positivity rate of 32.6% amongst pulmonary cases suggests their potential to spread disease and
emphasizes a need to review the contribution of children in transmission of TB within communities. Greater vulnerability of
the female child and considerable role of mother in disease transmission highlights a need to increase focus on females in
TB control programs in Pakistan.

Citation: Batra S, Ayaz A, Murtaza A, Ahmad S, Hasan R, et al. (2012) Childhood Tuberculosis in Household Contacts of Newly Diagnosed TB Patients. PLoS
ONE 7(7): e40880. doi:10.1371/journal.pone.0040880
Editor: T. Mark Doherty, Statens Serum Institute, Denmark
Received October 6, 2011; Accepted June 17, 2012; Published July 31, 2012
Copyright: ß 2012 Batra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: rumina.hasan@aku.edu

Introduction and diagnosis of TB in children routine screening of children in

close contact to infectious adult cases is thus recommended [10].
Tuberculosis (TB) remains a leading cause of morbidity and Pakistan ranks 8th on the list of 22 high TB burden countries
mortality in all age groups especially in developing countries [1]. with an incidence rate of 232/100,000 per year [11,12]. The
Of the 9 million annual TB cases worldwide, about 1 million DOTS program, implemented in the year 2002 was successful in
(11%) are estimated to be children (,15 years of age) [2,3,4]. This many aspects; however focus on childhood TB has been minimal.
figure varies from 3 to 25% in different countries [2]. However The exact prevalence of TB in children is not known. In
these results are based on smear positive cases and hence are likely accordance with data from the National Tuberculosis Control
to underestimate the magnitude of TB in children. Program Pakistan (NTP) (2001–2004), 4.4% of all smear positive
Childhood TB remains a neglected entity due to the fact that cases are children under 15 years of age [13]. Given the significant
majority of the cases are smear negative thus considered to role of adult patients in disseminating disease to children, this
contribute less towards disease spread [5,6]. Moreover the analysis was conducted to assess the burden of TB in children
difficulty in accurately diagnosing pulmonary disease in children among the household contacts of new TB patients in Karachi
remains a significant barrier in addressing the issue of childhood Pakistan.
TB [5,7,8].
While role of childhood TB in disease transmission may be Methods
lower than that of adult disease, childhood TB contributes towards
a reservoir from which a significant number of future adult cases A retrospective analysis of children (,15 years) who were
arise. Furthermore children are substantially at higher risk of household contacts of new adult TB patients, presenting to 9
developing severe forms of the disease such as miliary TB and TB Marie Adelaide Leprosy Center (MALC) field clinics in Karachi
meningitis [3]. Childhood TB moreover, usually suggests recent between January 1, 2008 to December 31, 2010 was conducted.
transmission, most commonly from an infectious adult with These clinics are located in 9 of the 18 administrative units of
pulmonary or cavitary disease [9]. To enhance early identification Karachi, where TB treatment is provided free of cost. This

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 Childhood Tuberculosis

community based model is a well recognized program both in Table 1. Characteristics of children diagnosed with
Pakistan and internationally and has high credibility in the tuberculosis (n = 121).
communities in which it operates. MALC routinely screens all
household contacts and offers treatment to those diagnosed with
TB. Characteristics n %
For this study, household contact was defined as a child
Age of child (years)
(,15 years) living in the same house as the adult patient with TB.
Those children who had previously received or were on TB Mean (6SD) 11.7 (62.8)
treatment at the time of inclusion were excluded. Detailed history 1–5 6 5
and clinical examination of children in contact with a diagnosed 6–10 27 22.3
TB patient is routinely carried out as part of MALC’s TB 11–14 88 72.7
program. Initial screening criteria used to identify suspected TB
Sex
cases included low grade fever and weight loss. Additional criteria
were cough for more than 3 weeks for pulmonary TB, and Male 32 26.4
localizing signs/symptoms including palpable lymph nodes, Female 89 73.6
headache/vertigo, backache, and loss of sensation for extrapul- Type of TB
monary TB. Children suspected of having pulmonary TB are Pulmonary 89 73.6
encouraged to provide morning sputum for microscopy. Three
Extra pulmonary 32 26.4
morning sputum samples are examined for each child. Chest X-
Sputum smear1
ray and tuberculin skin test (TST) is carried out by the clinic staff
(treating physician) in those unable to produce sputum and those Negative 45 60.8
found to be sputum smear negative on microscopy. TST is Positive (1+) 14 18.9
performed using five tuberculin units (TU) of tuberculin purified Positive (2+) 6 8.1
protein derivative (PPD)-S with .5 mm induration as cut off. Positive (3+) 9 12.1
Extrapulmonary TB is diagnosed on basis of clinical information,
Treatment outcome
TB relevant investigations including fine needle aspiration
cytology for lymph node TB, detailed report of pleural effusion Treatment completed 88 72.7
for TB of the pleura, skin biopsy for skin TB, TST and MRI/CT Cured 26 21.5
scans. Cases of TB are defined in accordance with WHO Treatment failure 1 0.8
recommendation. Response to therapy is also monitored. Died 4 3.3
Data was entered and analyzed in SPSS version 19 (IBM SPSS,
Out transferred 1 0.8
Chicago, IL, USA). Descriptive statistics were computed for all
Defaulted 1 0.8
variables. Means (6 Standard deviation) were calculated for
continuous variables while frequencies (%) for categorical vari- Source case relationship to child*
ables. Chi square test was used to assess associations. Mother 51 42.1
Father 18 14.9
Ethics statement Sister 31 25.6
Specific ethical approval for the study and consent from the Brother 27 22.3
patients was not needed as the data was taken from patient record
Cousin 7 5.8
maintained by Marie Adelaide Leprosy center (MALC) as part of
good clinical practice. At registration MALC advises patients and No. of source cases
takes verbal consent that the recorded data may be used One 108 89.2
anonymously in reports, publications and presentations. For this Two 13 10.8
study the data was used anonymously. Sex of source case2*
Male 44 38.3
Results
Female 76 66.1
A total of 1994 adult patients were diagnosed with TB during 1
For 47 children sputum was not obtained.
the study period. Of these 16% (n = 320) had extra-pulmonary 2
For 6 children sex of the contact source case was not known.
TB. Among those with pulmonary TB, 65% (n = 1089) were smear *Multiple response questions.
positive. doi:10.1371/journal.pone.0040880.t001
Household contacts of the 1994 adult TB cases were screened.
These included 6613 child contacts (,15 years) of which 2662 exudative pleural effusion and in 6 cases the diagnosis was made
(40.25%) were males and 3951 (59.7%) females. Of the total on the basis of MRI or CT scan findings.
children screened, 317 were suspected on the basis of screening Mean age of these diagnosed children was 11.7 (62.8) years.
criteria and 121 (1.8%) diagnosed with TB (Table 1). Majority (72.7%) were between 11–14 years age group. TB was
Pulmonary TB was diagnosed in 89 (73.6%) cases, of which 29 diagnosed in 2.3% (n = 89) of female and 1.2% (n = 32) of male
(32.6%) were sputum smear positive, 43 were diagnosed on the child contacts screened. Disease was found to be significantly
basis of chest X’ray changes and TST positivity, 2 on chest X’ray higher among female compared to male children screened (p-value
and clinical grounds while 15 were diagnosed on basis of TST ,0.01).
positivity and clinical features. Extrapulmonary TB was diagnosed The commonest relationship of source cases to diagnosed
in 32 (26.4%) children, of which 28 were TST positive. These children was the mother (n = 51, 42.1%) followed by sister (n = 31,
included 19 with histologically confirmed lymph nodes, 2 with 25.6%), brother (n = 27, 22.3%) and father (n = 18, 14.9%). The
biopsy proven skin TB, 5 diagnosed on the basis of lymphocytic source case was a female for 66.1% (n = 76) of the children.

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 Childhood Tuberculosis

Treatment was completed on 88 (72.7%) cases; while an earlier studies that have also reported a relatively higher frequency
additional 26 (21.5%) were cured. WHO criteria were used for of TB in female children [18,19,20]. These findings call for further
treatment completed and cured [2]. Cured was thus defined as an research, to better understand the gender differences identified in
initial smear-positive TB patient who is sputum smear-negative in this study.
the last month of treatment and on at least one previous occasion. Higher frequency of mothers being reported as the contact of
There was 1 (0.8%) treatment failure (remained sputum smear- diagnosed TB children is consistent with a number of previous
positive at 5 months or later after starting treatment), 4 (3.3%) studies [21]. The most likely explanation may be the fact that
patients died, 1 (0.8%) was transferred out and 1 (0.8%) defaulted. children are close to mothers and spend more time with them.
However, this may also be a consequence of the fact that women
Discussion tend to be diagnosed and treated late, hence are more likely to
transmit disease [22]. Social marginalization of women creates
The study showed that 1.8% of children in household contacts
gender disparities in access to health care. Additionally the stigma
of adult TB patients also had TB. Consistent with earlier reports,
associated with TB is likely to affect women more than men.
extrapulmonary disease was higher (27.3%) among children as
Generally speaking women are also more likely to neglect their
compared to the adults (16%) [3]. In view of the limited sensitivity
of sputum smear microscopy in children, the number of childhood illness and thus develop advanced disease [23].
pulmonary TB cases being reported however is likely to be an In conclusion, our data suggests a need to review the
under-estimate. Lack of specificity as well as reader variation in assumption that children do not contribute significantly to TB
radiological interpretation is a further limitation of this study. transmission. Greater vulnerability of the girl child and consider-
Despite these limitations a smear positivity rate of 32.6% amongst able role of the mother in disease transmission emphasizes a call
children with pulmonary TB suggests that children are likely to be for increased focus on women and female children in the TB
a source of disease spread within this population. The data further control programs in Pakistan.
suggests that the assumption that children do not contribute
significantly to disease transmission needs to be reviewed. Acknowledgments
The significantly higher number of girls among children We would like to acknowledge Dr Kausar Jabeen for reviewing the paper.
diagnosed with TB is alarming. The link between nutritional We would also like to thank the staff and management of Marie Adelaide
deficiency and tuberculosis has long been recognized [14,15]. It is Leprosy center for their help in this study.
possible to hypothesize that higher frequency of disease in the
females may reflect poor nutritional status of the girl child in this Author Contributions
region, making them more vulnerable to the disease [16,17]. Such
an association however needs to be further investigated in the Conceived and designed the experiments: SB AA RH RP. Performed the
context of childhood tuberculosis in this country. Higher experiments: SB AM SA. Analyzed the data: AA. Contributed reagents/
materials/analysis tools: SB AA. Wrote the paper: AA RH.
frequency of disease in the girl child moreover is consistent with

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