Conventional TB diagnostics for children involved appropriate use of clinical details, chest radiology and tuberculin skin test, with much less focus on micro-biology, due to poor yield (AFB smear) or access issues (MTb cultures). U-DST strategy has led to change in the diagnostic pathways to include NAAT for every patient where a biological specimen can be procured. Routine chest imaging is done as initial screening test as testing of respiratory specimens from radiologically positive cases improves the yield of NAAT [4,5].

While NAAT has higher sensitivity than the smear, yet it fails in many paucibacillary cases. It is good only as a ‘rule in’ test and a negative NAAT does not rule out TB. The conventional methods of clinical diagnosis still need to be relied upon among those who are not confirmed by molecular tests. Current algorithm for evaluation of a child with pulmonary TB is shown in Fig. 1.

Treatment of TB has also evolved from erstwhile standard regimens based on the likely risk of drug resistance (new versus retreatment cases) to regimens based on identification of key resistance. The evidence available earlier in 70s suggested that the retreatment cases could be treated with a simpler 5 drug category II regimen. However, post implementation operational research and meta-analysis showed that this strategy was associated with increased risk of treatment failure with amplification of resistance to other companion drugs, particularly, if the patient was initially harboring rifampicin resistance [3,6]. With the feasibility of upfront rapid testing for rifampicin resistance, use of standard regimens without sensitivity testing is no more recom-mended for both the new as well as retreatment cases.

Likewise, the non-responders to initial regimen for drug sensitive TB (by 4 weeks) should be assessed again for presence of drug resistance (rifampicin and isoniazid at least). Non responsive cases with resistance to rifampicin and/or isoniazid are also tested for resistance to second line drugs like fluoroquinolones and the injectable aminoglycosides to provide the most suited regimens depending on the resistance pattern. The effort is to manage the cases as per the sensitivity to key drugs, thus improving outcomes and preventing further ampli-fication of drug resistance. Retreatment cases with-out rifampicin resistance are now treated again with initial 4 drug regime while being tested for isoniazid resistance. In case of isoniazid (mono- or poly-) resistance, 6 month uniphasic 4 drug regime, where isoniazid is replaced by levofloxacin, is recommended. The IAP NTEP 2020 TB treatment guidelines are shown in Table I and II. The algorithm for evaluation of children with suspected drug resistance is shown in Fig. 2.

NTEP has introduced daily therapy with dispersible tablets in fixed dose combinations (FDC) for children. Younger children get 3-drug FDCs (HRZ) along with 100 mg ethambutol tablets. Older children can also get, in addition, 4-drug FDCs (RHZE) to meet their drug dosages (Table III). Isoniazid and rifampicin are in a ratio of 2:3 and the average dose of isoniazid is around 10 mg/kg/day. These drugs are given free of cost in public sector and the private sector can also access these drugs for free through various partnership schemes that the program offers.

Goal to eliminate TB cannot be achieved timely unless the pool of cases with latent infection is treated. TB preventive treatment may now be extended to all household contacts of an infectious case after ruling out disease by symptom screening in line with WHO guidance. For children above 5 years, if facilities exist, one may test for presence of latent infection and then treat. But it is not mandatory to test for infection due to lack of simple and affordable point of care tests. TB preventive treatment is also recommended for any tuberculin skin test positive child who is receiving immunosuppressive therapy (children with nephrotic syndrome, acute leukemia, etc.), and a child born to mother who was diagnosed to have TB in pregnancy but has no evidence of disease [7].

Isoniazid is recommended for TB preventive treatment at a dose of 10 mg/kg/day for six months. No drugs are currently recommended for TB preventive therapy for the contacts of MDR TB cases but a close follow up for two years after exposure is recommended for timely identification of those developing disease among exposed [8].

To conclude, the management of TB in children now has undergone a sea change with drug sensitivity directed therapy becoming the corner pillar. NTEP approved rapid NAAT has become the core investigative modality and erstwhile clinic-radiological approach of diagnosis is used only when NAAT fails in a clinically probable case. The pediatricians need also to be aware of the updated guidelines detailing change in regimens and drug dosages so that they can rationally manage TB among children.

Contributors: Both authors contributed to reviewing the literature, drafting, correcting and finalizing the manuscript.

Funding: None; Competing interest: None stated.

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2. Ministry of Health with Family Welfare. National Strategic Plan for Tuberculosis: 2017-25. Revised National Tuberculosis Control Programme. March 2017. Accessed September 16, 2020. Available from: https://tbcindia. gov.in/WriteReadData/National%20Strategic %20Plan% 202017-25.pdf

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