European Journal of Cardiovascular Medicine

Tuberculosis (TB) remains one of the leading infectious causes of death worldwide, and children constitute a particularly vulnerable group because of immature cell-mediated immunity and a higher propensity to progress from infection to active disease. [1] Globally, an estimated 1.25 million children fall ill with TB every year, contributing to nearly 11% of the total TB burden, yet childhood TB continues to be under-diagnosed and under-reported in national programmes. [2]

India carries the highest burden of TB in the world, accounting for over one-quarter of the global TB cases and a substantial share of paediatric TB cases. [3] As per the India TB Report published by the Central TB Division, Ministry of Health and Family Welfare, children below 14 years of age account for approximately 6–8% of all notified TB cases under the National TB Elimination Programme (NTEP), although this is likely an underestimate of the true burden because of diagnostic difficulties in this age group. [4]

Diagnosis of TB in children is inherently more challenging than in adults. Childhood TB is typically paucibacillary in nature, children are often unable to produce sputum, and the clinical presentation is frequently non-specific, overlapping with common childhood illnesses such as pneumonia, malnutrition and other chronic infections. [5] Conventional bacteriological tools such as sputum smear microscopy for acid-fast bacilli (AFB) have a low sensitivity in children, often not exceeding 10–15%, necessitating reliance on a combination of clinical, radiological, immunological and, where available, molecular criteria for diagnosis. [6]

The introduction of the Cartridge Based Nucleic Acid Amplification Test (CBNAAT/Xpert MTB/RIF) under the NTEP has improved the bacteriological confirmation rate in children to some extent by allowing rapid detection of Mycobacterium tuberculosis and rifampicin resistance from gastric aspirate, induced sputum, and extrapulmonary specimens. [7] Several Indian studies have highlighted that despite the availability of CBNAAT, a large proportion of paediatric TB cases are still diagnosed clinically because of the paucibacillary nature of disease and difficulty in obtaining adequate specimens from young children. [8]

Extrapulmonary tuberculosis (EPTB) is disproportionately more common in children than in adults, with tubercular lymphadenitis, tubercular meningitis, abdominal tuberculosis and osteoarticular tuberculosis being frequently encountered forms in Indian paediatric case series. [9] Malnutrition, HIV co-infection, and close contact with a sputum-positive adult TB case have consistently been identified as important risk factors for the development of active TB disease in children in studies from the Indian subcontinent. [10]

Treatment outcomes in childhood TB are generally more favourable than in adults when therapy is initiated promptly and adherence is ensured, largely due to lower rates of drug resistance and better immune response; however, delayed diagnosis, malnutrition, and loss to follow-up continue to adversely affect outcomes in resource-limited settings. [11] With the NTEP's shift towards daily fixed-dose combination regimens and weight-band based dosing for children, treatment success rates have improved, though real-world data from tertiary care centres in India remain limited. [12]

Given the continuing burden of paediatric TB in India, the diagnostic difficulties peculiar to this age group, and the paucity of recent Indian data from tertiary teaching hospitals correlating clinical presentation with diagnostic yield and treatment outcome, the present study was undertaken to describe the clinical profile, document the diagnostic challenges encountered, and evaluate the treatment outcomes of children with tuberculosis managed at a tertiary care teaching hospital.

Study Design and Setting

This was a hospital-based prospective observational study conducted in the Department of Paediatrics of a tertiary care teaching hospital over a period of two years (January 2022 to December 2023).

Study Population

All children aged 0 to 14 years who were diagnosed with tuberculosis  as per the standard case definitions of the National TB Elimination Programme (NTEP) and admitted to, or registered for follow-up at, the DOTS centre of the hospital during the study period were considered for inclusion.

Inclusion Criteria

(1) Children aged 0–14 years with a confirmed or clinically diagnosed diagnosis of pulmonary or extrapulmonary tuberculosis as per NTEP criteria; (2) children whose parents/guardians gave written informed consent for participation.

Exclusion Criteria

(1) Children already on anti-tubercular therapy for more than two weeks at the time of presentation; (2) children with incomplete case records; (3) parents/guardians not willing to give consent.

Sample Size

Based on the average annual case load of paediatric TB registered at the study centre and considering a study period of two years, a total of 150 children satisfying the inclusion criteria were enrolled by consecutive sampling.

Data Collection

A predesigned, pretested proforma was used to record demographic details (age, sex, residence, socioeconomic status), history of contact with an adult TB case, immunisation (BCG) status, presenting symptoms and their duration, anthropometric measurements (weight, height, mid-upper arm circumference) with nutritional grading as per WHO/IAP growth charts, and relevant past history including HIV status. All children underwent a detailed clinical examination and were evaluated with a battery of investigations including Mantoux tuberculin skin test, chest radiograph, sputum/gastric aspirate/induced sputum examination for AFB by Ziehl–Neelsen (ZN) staining, CBNAAT (Xpert MTB/RIF), mycobacterial culture where feasible, relevant imaging (ultrasonography, contrast-enhanced CT/MRI) and histopathological/cytological examination of tissue/fluid samples as clinically indicated. Diagnosis was made as per NTEP paediatric TB diagnostic algorithm, classifying cases as bacteriologically confirmed or clinically diagnosed.

Treatment and Follow-up

All enrolled children were started on anti-tubercular therapy (ATT) as per NTEP weight-band based daily regimen and registered on the portal. Children were followed up monthly during the intensive phase and two-monthly during the continuation phase, with clinical, anthropometric and, where indicated, radiological reassessment. Treatment outcomes were recorded at the end of therapy as cured, treatment completed, treatment failure, died, lost to follow-up, or not evaluated, as per standard NTEP definitions.

Ethical Considerations

The study was approved by the Institutional Ethics Committee prior to commencement. Written informed consent was obtained from parents/legal guardians of all participating children, and assent was obtained from children above 7 years of age where applicable. Confidentiality of patient data was maintained throughout the study.

Statistical Analysis

Data were entered in Microsoft Excel and analysed using SPSS software (version 25.0). Categorical variables were expressed as frequencies and percentages, and continuous variables as mean ± standard deviation (SD) or median (interquartile range) as appropriate. Association between categorical variables was assessed using the Chi-square test or Fisher's exact test, with p < 0.05 considered statistically significant.

A total of 150 children diagnosed with tuberculosis were enrolled during the two-year study period. The demographic, clinical, diagnostic and treatment outcome data are summarised in Tables 1 to 8.

Demographic Profile

The mean age of children in the study was 6.8 ± 3.4 years, with the maximum number of cases (38.7%) seen in the 5–9 year age group. Boys (53.3%) outnumbered girls (46.7%), giving a male to female ratio of 1.14:1. A majority of children (64.7%) belonged to a rural background, and 58.0% belonged to lower and lower-middle socioeconomic status as per the modified Kuppuswamy classification (Table 1).

Table 1: Demographic Profile of Study Participants (n = 150)

Clinical Presentation

Fever was the commonest presenting symptom (88.7%), followed by cough (76.7%), weight loss or failure to thrive (68.7%), loss of appetite (61.3%) and lethargy/fatigue (44.0%). Among extrapulmonary presentations, peripheral lymphadenopathy (17.3% of total cases), abdominal distension/pain (8.7%) and altered sensorium/seizures suggestive of CNS TB (4.7%) were notable. The mean duration of symptoms prior to diagnosis was 6.2 ± 3.1 weeks (Table 2).

Table 2: Clinical Presentation of Study Participants (n = 150)

Note: Percentages do not add up to 100 as more than one symptom was present in most children.

Type and Site of Tuberculosis

Pulmonary TB (PTB) was diagnosed in 94 children (62.7%) while extrapulmonary TB (EPTB) accounted for 56 children (37.3%). Among extrapulmonary cases, tubercular lymphadenitis was the most common (35.7% of EPTB cases), followed by abdominal/gastrointestinal TB, tubercular meningitis, pleural effusion, and osteoarticular/spinal TB (Table 3), a distribution comparable to that reported from other Indian paediatric case series. ^[9]

Table 3: Distribution of Cases by Type and Site of Tuberculosis (n = 150)

Diagnostic Modalities and Challenges

Only 37 children (24.7%) were bacteriologically confirmed by smear microscopy, CBNAAT or culture, while the remaining 113 children (75.3%) were diagnosed clinically based on a composite of history, examination, radiology and Mantoux/IGRA positivity, reflecting the well-recognised paucibacillary nature of childhood TB. ^[5,6]

Mantoux test was positive (induration ≥10 mm, or ≥5 mm in immunocompromised/severely malnourished children) in 96 children (64.0%). Chest radiograph was abnormal in 108 of the 94 children with pulmonary TB and additional children with miliary/disseminated disease (79.4% of children imaged), the commonest findings being hilar/mediastinal lymphadenopathy, parenchymal infiltrates, and miliary mottling. CBNAAT was performed in 128 children from whom an adequate specimen (gastric aspirate, induced sputum, or extrapulmonary fluid/tissue) could be obtained and was positive in 35 children (27.3% of those tested; 23.3% of the total study population), which was higher than the yield of ZN-stained smear microscopy (10.7% of the total study population). Difficulty in obtaining adequate sputum specimens in younger children, the need for invasive procedures (gastric aspiration, fine needle aspiration, biopsy) for confirmation, and the relatively low sensitivity of available bacteriological tests were the major diagnostic challenges encountered (Table 4 and Table 5).

Table 4: Diagnostic Modalities Used and Their Yield (n = 150)

Table 5: Basis of Diagnosis (n = 150)

Nutritional Status and Risk Factors

Malnutrition (weight-for-age/BMI-for-age below –2 SD) was present in 68 children (45.3%), of whom 21 (14.0%) had severe acute malnutrition. HIV co-infection was documented in 4 children (2.7%). These findings are consistent with previous Indian studies that identify malnutrition as both a risk factor for, and a consequence of, childhood tuberculosis. ^[10]

Table 6: Nutritional Status and Associated Risk Factors (n = 150)

Treatment Outcome

All 150 children were initiated on NTEP-based daily weight-band ATT regimen. At the end of treatment, a favourable outcome (cured or treatment completed) was recorded in 131 children (87.3%). Seven children (4.7%) were lost to follow-up, 5 children (3.3%) died (of whom 3 had disseminated/miliary TB or tubercular meningitis at presentation), 4 children (2.7%) had treatment failure requiring regimen modification, and 3 children (2.0%) were transferred out (Table 7). ^[11,12]

On sub-group analysis, children with extrapulmonary TB, severe malnutrition, and delayed presentation (symptom duration >8 weeks) had a statistically significant association with unfavourable outcomes (death/lost to follow-up/treatment failure) compared to those with pulmonary TB, normal nutrition and early presentation (p < 0.05) (Table 8).

Table 7: Treatment Outcome of Study Participants (n = 150)

Table 8: Factors Associated with Unfavourable Treatment Outcome (n = 150)

The present study, conducted on 150 children with tuberculosis at a tertiary care teaching hospital, found a mean age of 6.8 ± 3.4 years with maximum cases in the 5–9 year age group and a slight male preponderance (male to female ratio 1.14:1), findings that are broadly comparable to those reported by Kumar et al. and other Indian paediatric TB series, which similarly observed peak incidence in the early school-going age group. [13] A rural predominance and lower socioeconomic status among affected children in the present study is consistent with the well-documented association between poverty, overcrowding and TB transmission described in Indian community-based studies. [14]

Fever, cough, and weight loss/failure to thrive were the predominant presenting symptoms in this study, similar to the clinical spectrum reported by Swaminathan and Rekha in their review of paediatric tuberculosis management. [15] The non-specific nature of these symptoms, overlapping considerably with common respiratory and nutritional disorders of childhood, remains one of the principal reasons for diagnostic delay, a challenge also highlighted in a hospital-based study from North India by Sharma et al. [16]

Pulmonary TB was more common (62.7%) than extrapulmonary TB (37.3%) in this study, with tubercular lymphadenitis being the commonest extrapulmonary form, a pattern that closely mirrors the distribution reported in a large paediatric case series from a tertiary centre in South India by Ramachandran et al. and in earlier work by Seddon and Shingadia on the global epidemiology of childhood TB. [9,17] The relatively higher proportion of extrapulmonary disease in children compared to adults is attributed to lymphohematogenous dissemination that occurs more readily in the immunologically immature paediatric host. [18]

Bacteriological confirmation was achieved in only 24.7% of children in the present study, which is comparable to confirmation rates of 20–30% reported in other Indian tertiary care studies and reflects the inherent paucibacillary nature of childhood TB rather than a deficiency of the diagnostic algorithm used. [6,19] CBNAAT showed a higher positivity rate (27.3% among those tested) than conventional smear microscopy (11.3%), corroborating the findings of Nicol et al. and Sekadde et al., who demonstrated the superior sensitivity of Xpert MTB/RIF over smear microscopy for detection of Mycobacterium tuberculosis in paediatric respiratory and extrapulmonary specimens. [20,21] An Indian multicentric evaluation by Sachdeva et al. similarly reported improved case detection in children following the programmatic scale-up of CBNAAT under NTEP, while cautioning that specimen adequacy remains a persistent limiting factor in young, non-expectorating children. [22]

The difficulty of obtaining good-quality respiratory specimens from young children, the need for relatively invasive procedures such as gastric aspiration and fine needle aspiration cytology for extrapulmonary sites, and the low overall bacteriological yield despite comprehensive testing observed in this study are consistent with diagnostic challenges described extensively in the global paediatric TB literature. [5,23] These findings reinforce the continued reliance on composite clinical-radiological-immunological criteria, as recommended by WHO and adapted in the NTEP paediatric TB diagnostic algorithm, for the majority of childhood TB diagnoses in resource-limited settings. [24]

Malnutrition was documented in 45.3% of children in the present cohort, similar to the prevalence reported by Chandrasekaran et al. among children with TB in a South Indian tertiary hospital, and severe acute malnutrition was significantly associated with unfavourable treatment outcome in the present study, an association also noted by Jaganath and Mullins in their review of nutrition and paediatric TB outcomes. [25,26] This bidirectional relationship between malnutrition and TB — malnutrition predisposing to active disease progression, and TB in turn worsening nutritional status — underscores the importance of integrating nutritional rehabilitation with anti-tubercular therapy, as recommended in recent NTEP nutritional support guidelines (Nikshay Poshan Yojana). [27]

The overall favourable treatment outcome of 87.3% in this study is comparable to outcomes reported from other Indian tertiary care centres following the transition to daily fixed-dose combination ATT regimens, and is somewhat better than outcomes reported under the earlier intermittent regimen era described by Chadha and Praveen. [28,29] Extrapulmonary disease, severe malnutrition and delayed presentation beyond eight weeks were significantly associated with unfavourable outcomes in this study, findings that parallel observations by Devrim et al. and Oliwa et al. regarding predictors of poor outcome in childhood TB, and which emphasise the need for early case detection, particularly through active contact screening of children exposed to adult index cases. [30,31]

Loss to follow-up (4.7%) and mortality (3.3%) in this study, though relatively low, remain areas of concern and are consistent with figures reported from other Indian paediatric TB cohorts, where socioeconomic constraints, migration, and lack of caregiver awareness have been identified as major contributors to non-adherence. [32] Strengthening of the Nikshay-based digital follow-up system, community-level DOTS providers, and family-centred counselling, as recommended by the NTEP operational guidelines, may further improve adherence and reduce attrition in the paediatric age group. [33]

The strengths of this study include its prospective design, comprehensive diagnostic work-up including CBNAAT for the majority of children, and structured follow-up to document end-of-treatment outcomes. Limitations include the single-centre, tertiary-care hospital setting, which may not be representative of the community burden and spectrum of paediatric TB, a relatively short follow-up restricted to the treatment period without assessment of post-treatment sequelae, and the inability to perform drug susceptibility testing in all bacteriologically confirmed cases. Multicentric studies with longer follow-up and inclusion of primary and secondary care settings are required to validate these findings on a wider scale.

Paediatric tuberculosis in this tertiary care teaching hospital predominantly affected school-going children from rural and lower socioeconomic backgrounds, presenting with non-specific symptoms of fever, cough and weight loss. Pulmonary TB was more common than extrapulmonary TB, with tubercular lymphadenitis being the leading extrapulmonary manifestation. Bacteriological confirmation remained low, reaffirming the paucibacillary and diagnostically challenging nature of childhood TB, though CBNAAT offered a meaningfully higher yield than conventional smear microscopy. Malnutrition, extrapulmonary disease and delayed presentation were significant predictors of unfavourable treatment outcome. Overall, treatment success under the NTEP daily regimen was achieved in the large majority of children. Strengthening contact screening, nutritional support, molecular diagnostic capacity, and follow-up mechanisms are essential strategies to improve early case detection and treatment outcomes in childhood tuberculosis, and are central to achieving national and global TB elimination targets.

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