Anupama Mauskar, Vaidehi Hardas, Nusrat Inamdar.
Department of Pediatrics, HBTMC and Dr R N Cooper Hospital, Mumbai, India.
ADDRESS FOR CORRESPONDENCE
Nusrat Inamdar, 304-Adhikari Niwas, HBTMC and Dr R N Cooper Hospital. Vile Parle West. Mumbai 400056.
Email: nusratinamdar@gmail.com | | Abstract | Background: The incidence of childhood DSTB as well as DRTB is on rise. Extra-pulmonary TB equally contributes to pulmonary TB with highest mortality of neurological TB in children. Despite the very high disease burden, there are very few studies on tuberculosis among Pediatric population. In this case series we wish to discuss the difficulties in diagnosis of Pediatric TB along with clinical presentation, microbiological, radiological reports, treatment given and outcome.
Clinical Description: Total 24 Pediatric patients (Age range 5months to 12 years) with diagnosis of tuberculosis (from March 2024 to December 2024) were included in this case series. Patients were categorised as per age, sex, nutritional status, pulmonary/extra-pulmonary TB and DSTB/DRTB (as per The National Tuberculosis Elimination Programme guidelines ). Pulmonary Tuberculosis was most common form followed by neurological TB. Malnutrition was contributory factor in 58.3% cases.
Management & Outcome: Treatment was given as per NTEP guidelines. The outcome was noted as discharge, death and lost to follow up.
Microbiological confirmation was reported to be more than 30%.The mortality was 12.5% (Age was 5 months, 5 years, and 10 years, 2 females, one male). The mortality was highest in CNS TB. The rate of MDR TB was 8.3 %.
Conclusion: Despite increasing incidence of childhood TB, microbiological yield of tubercular bacilli is very poor in children which poses difficulty and delays in the diagnosis. Therefore to develop a robust, highly sensitive, non-invasive and cheaper diagnostic tool is the urgent need of the hour to achieve the strategic goal set up by WHO for reduction of overall TB worldwide. | | | | Keywords | | Childhood TB burden, Diagnostic Difficulties, Childhood TB outcome. | | | | Methods | A global total of 8.2 million people were reported as newly diagnosed TB in 2023, India accounts for 26% of global TB burden.1 Among the global TB burden in 2023, 55% of people were men, 33% women and 12% were children and young adolescents.2,3 The net reduction in the TB incidence rate between 2015 and 2023 was 8.3%, far from the WHO End TB Strategy milestone of a 50% reduction by 2025.1
The actual burden of paediatric TB is not known due to diagnostic difficulties but has been assumed that 10% of total TB load; with more than 100,000 estimated deaths every year, it is one of the top 10 causes of childhood mortality.4
In India, approximately 3.42 lakh children (0-14 years of age) are estimated to get TB every year, and account for about 6% of total TB cases reported to NTEP in 2020-21.5 Nearly a third of the children with TB globally are from India, despite an estimated detection gap of about 56%.6
Pulmonary TB is the most common form of TB in children; however, extra-pulmonary TB (EPTB) in children also forms a significant proportion of cases than adults .5 In general, younger children have paucibacillary TB that show up poorly on sputum smears.3
Despite the very high disease burden, there are very few studies on Paediatric tuberculosis. This case series highlights the clinical presentation, microbiological radiological reports, difficulties in diagnosis and treatment and outcome.
Clinical Description:
Total 24 tuberculosis diagnosed Pediatric patients (March 2024 to December 2024) both outdoor and indoor were included in this case series.
They were categorised as per age, sex, nutritional status (using WHO charts & IAP BMI charts). Their HIV status, BCG vaccination status, Mantouxreaction, TB contact history, prior treatment, geneXpert, MGIT and radiological reports were recorded. They were categorised into pulmonary/extra-pulmonary TB and DSTB/DRTB (as per NTEP guidelines). Treatment was given as per NTEP guidelines. The outcome was noted as discharge, death and lost to follow up.
Clinical profile is mentioned here in the tables (Tables I and II).
Table 1. Demographic Profile and Clinical Details of the cases.
| Age /Sex wise distribution of patients (n=24) |
Nutritional Status (Normal in 10 children) |
| Age |
0 to 5 years |
>5years |
FTT (below 6 mo)
01 |
SAM /MAM (6 mo to 5 yrs)
04 |
Undernourished as per BMI (children >5 yrs)
09 |
| Male |
5 |
6 |
00 |
01(Moderate Acute Malnutrition) |
04 underweight |
| Female |
3 |
10 |
01 |
03(Severe Acute Malnutrition) |
2 Underweight, 03 (severe thin) |
| Clinical Details |
| HIV Status |
BCG vaccinated |
History of contact |
Prior treatment with antibiotics |
Mantoux Test |
| Positive |
Negative |
Yes |
No |
Yes |
No |
Yes |
No |
Positive |
Negative |
| 0 |
24 (100%) |
24 (100%) |
0 |
8 (33%) |
16 (66%) |
16 (66%) |
8 (33%) |
10 (41.6%) |
14 (64.4%) |
|
Table 2. Presenting symptoms and Distribution of Pulmonary / Extra-pulmonary TB.
| Presenting symptoms |
| Symptom |
Present |
| Fever |
19 (79%) |
| Cough |
10 (41%) |
| Vomiting |
13 (54%) |
| Headache |
04 (16.6%) |
| Lymph node swelling |
3 (12.5%) |
| Abdominal pain |
7 (29.1%) |
| Distribution of Pulmonary / Extra-pulmonary TB |
| Type of TB |
Distribution |
No |
Total cases |
Clinical Diagnosis |
Abnormal Chest/spinal/bone Radiology/Neuroradiology |
GeneXpert/MGIT Positive |
| Respiratory |
Pulmonary |
4 |
10 |
Yes |
All 10 |
03 |
| |
Pleural |
1 |
| Pulmonary+Pleural |
2 |
| Pulmonary with lymph nodal |
3 |
| Disseminated |
|
2 |
02 |
Yes |
02 |
01(sputum sample positive) |
| Lymph Nodal |
Isolated lymph nodal |
3 |
03 |
Yes |
02 |
*01(FNACs/o caseous necrosis) |
| Skeletal |
Mastoiditis |
1 |
03 |
Yes |
00 |
*01 Rifa Resistance sample -pus from chest wall abscess |
| |
Ribs with chest wall abscess |
1 |
| C1,C2 Vertebra Pott’s Spine |
1 |
| Abdominal System |
Lymph nodal Intestinal |
1
1 |
02 |
Yes |
02 |
00 |
| Central Nervous System |
Tuberculoma |
5 |
07 |
Yes |
07 |
03
*1 Rifa Resistance sample was CSF (MGIT positive) |
| |
TBM |
2 |
*Two Rifampicin resistance Tuberculosis among 24 patients (8.3%)
Most common presenting symptom was fever present in 79 percent of patients (19 out of 24).
[Table3
Drug Sensitive and Drug Resistance TB - 2 of 24 cases were of rifampicin resistance on GeneXpert( 1st was Chest wall abscess, 2nd was TB Meningitis). MGIT was positive only in one Rifa resistance case of TB Meningitis.]
Management and Outcome:
Except two patients all received first line ATT as per NTEP guidelines. Two patients with rifampicin resistance were referred to higher centre for Rifa resistance TB treatment.
Twenty one out of 24 patients got discharged, are cured and doing well on follow up. One patient was non-compliant had lost to follow up and brought dead to hospital. She was a 5 months female with FTT with disseminated drug sensitive tuberculosis. Two other patients expired in the hospital, both had CNS TB – TB Meningitis, one was DSTB and other was Rifa resistance TB (CSF GeneXpert was positive for Tubercular Mycobacterium and rifampicin resistance).
Discussion & Review of Literature:
Diagnostic Difficulties & Challenges – Pulmonary TB
Out of 24 patients ten were pulmonary cases. Nine received prior antibiotics for fever and pneumonia, while one was treated for AGE. Because of no response they were referred to tertiary centre for further management. This caused delay in diagnosis & treatment. Patients presenting with pneumonia and pleural effusion are invariably treated with antibiotics first when there is no clue towards tuberculosis. Therefore a detailed history, weight record, history of contact, high index of suspicion, HRCT Chest and all efforts to document microbiological evidence must be practiced for early diagnosis and treatment.
A case of pulmonary TB was accidentally diagnosed, while under treatment for AGE with MAM. Chest X-Ray was abnormal & GL gene expert was positive. Later mother gave history of active TB in grandfather. Another case of pulmonary TB was treated for Pneumonia with pleural effusion did not respond to antibiotics. Both X ray & HRCT chest were suggestive of mediastinal lymphadenopathy. Sputum geneXpert repeated two times but first was negative and second was indeterminate. While awaiting third gene expert (again negative) patient developed seizures and CT Brain revealed multiple granulomas. She was started on first line ATT and got completely cured. Another case of pleural effusion not responding to treatment, all TB work-up was negative underwent surgical intervention for VATS & decortication. The pleural biopsy revealed tubercular granuloma.
Mediastinal lymphadenopathy needs CT guided biopsy and histopathology to confirm the diagnosis of TB when repeated sputum gene expert samples are negative without any other clues for TB. ,As a close differentials, underlying malignancy has to be ruled out.
Central nervous system (CNS) TB – There were seven cases of CNS TB out of which 2 were meningitis and 5 patients had tubercular granuloma.
A case of CNS TB presented with only two days history of fever, started on antibiotics but fever was persistent and his sensorium worsened so lumbar puncture was done and antibiotics were escalated. CSF was suggestive of tubercular meningitis. He later developed polyuria, severe hyponatremia, raised ICP and expired. His CSF geneXpert revealed MTB which was Rifa resistant.
Another five month old baby presented like bronchiolitis at 3 months of age later developed abdominal distention, which responded to meropenem. She developed third nerve palsy within a month after discharge and MRI Brain suggestive of tuberculoma with TB Meningitis, x-ray chest showed milliary TB. Her father had pulmonary TB and was non-compliant to treatment. She was brought dead few days after discharge.
A 6-year-old female child presented with atypical febrile seizure, neuroimaging revealed tubercular granuloma with mastoiditis of temporal bone. Pus gene expert was negative. She responded to first line ATT.
Skeletal TB-
A patient with Pott’s spine presented as para pharyngeal abscess initially which later turned out as pott’s spine.
Second case of rib osteomyelitis presented with chest wall abscess without any chronic symptoms. The surgeon and chest physician didn’t send pus for gene expert assuming it non-tubercular. The pus gene expert sent by us showed Rifa resistance. Patient is doing better on Rifa resistance ATT.
Abdominal TB-
Case of Abdominal TB with lymph node involvement was diagnosed on clinical plus radiological clue as microbiology was negative. This patient was having subacute intestinal obstruction and persistent vomiting. Giving ATT to a child with continuous vomiting was a challenge as no injectable alternative is available in first line drugs. Hence ATT was given through Ryle’s tube. There was also history of contact with MDR TB in elder sibling. Patient responded to first line ATT.
Lymph node TB-
A case with bilateral cervical lymphadenopathy without any constitutional symptoms but lymph node histopathology suggestive of tuberculosis also responded to first line ATT even though microbiologically negative.
Second case of mediastinal lymph nodal TB had constitutional symptoms of fever, weight loss and history of contact, microbiologically negative but responded to first line ATT.
We faced lot of challenges diagnosing these cases. In many cases (more than 50%) gene Xpert was negative even on repeat sampling. All that helped us in diagnosis was high index of suspicion and radiology. Similar difficulties were mentioned in the study by Jain SK et al from Pune; they do faced difficulties in diagnosis of TB in children and found only 3% culture positive (may be due to high rates of extra-pulmonary TB).7 In this case series also culture was positive only in one case of chest wall abscess (<1%) where Rifa resistance was also noted in geneXpert report.
Gene Xpert Assays was the first point-of-care assay for TB, and was endorsed by the WHO in 2010 (WHO Guidelines Approved by the Guidelines Review Committee, 2011). Xpert has demonstrated improved efficacy in detecting intrapulmonary and extrapulmonary TB.8 However, as per Kay et al., 2020 the sensitivity of Xpert has been found to vary depending on the specimens used for analysis, namely sputum, stool, bronchoalveolar lavage fluid (BALF), gastric juice, interstitial fluid, and biopsies. Xpert’s estimated specificity among all specimens is generally higher than 98%.9
We did not do Gene Xpert ultra for our patients because of unavailability of test, however as per the available literature it is more sensitive. Gene Xpert Assays limit of Detection is 112.6 bacterial colony forming units/L and it has poor sensitivity in detecting paucibacillary cases.
Gene Xpert Ultra has a limit of detection of 15 CFU/L and thus is recommended by WHO to be used in children as well adults to increase the overall sensitivity of MTB detection. However the increase in sensitivity is accompanied by a slight decrease in specificity leading to higher number of false positive results. Thus, the results of Gene Xpert Ultra require clinical correlation in culture negative specimens.10 Pulmonary tuberculosis was most common form followed by neurological TB in the study reported by Kumar A, which is similar to above case series (10 pulmonary, 7 CNS TB among total 24 patients).11
Malnutrition was potent contributory factor (91.8%) in the study by Kumar A. while it was 58.3% in above case series.11
Microbiological confirmation was reported to be 8.8% in the study by Tripathi BB 12 while it was more than 30% in our case series.
The mortality rate in the above case series was 12.5% (Age was 5 month,5 years and 10 years, with 2 females, 1 male), similar mortality rate (13.8%) was reported by Tripathi BB, 12 while mortality rate of 9.5% was reported by Kumar A.11
The mortality was highest in CNS TB (70%) in the study by Tripathi BB,12 which is similar to the present case series where all 3 patients died of tubercular meningitis, one also had disseminated form of disease.
The rate of MDR TB was 8.3 % in the current study ,it was reported to be 7.3% in the study by Mauskar et al 11 ;7% in the study by Shah and Chilkar,14 and was less than 2% in the study by Jain SK.7 | | | | Conclusion | | The incidence of childhood DSTB as well as DRTB is on rise. Extra-pulmonary TB equally contributes to pulmonary TB with highest mortality of neurological TB in children. Microbiological yield of tubercular bacilli is very poor in children which poses difficulty and delays in the diagnosis. Detailed clinical evaluation, screening of all high risk cases, emphasis on microbiological evidence and supportive radiological investigations if clinically indicated can help in early diagnosis, treatment and improve outcome. | | | | Compliance with Ethical Standards | | Funding None | | | | Conflict of Interest None | | |
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| Cite this article as: | | Mauskar A, Hardas V, Inamdar N. Diagnostic Difficulties and Challenges of Pediatric Tuberculosis – Review through a Case Series. Infection Child J. 2026;1. |
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