Consolidated Guidelines

Children with severe acute malnutrition (SAM): four studies (with 259 participants, of whom 9 had TB disease) were identified for children with SAM using Xpert Ultra on gastric aspirates and three studies (428 participants, 19 with TB) using Xpert Ultra on stool specimens. The meta-analysis on stool samples in children with SAM showed similar accuracy as in the overall analysis (sensitivity 63.2%, specificity 98.5%). A meta-analysis on gastric aspirates could not be performed due to insufficient data.

The development of the Xpert MTB/RIF assay (Cepheid, Sunnyvale, United States of America (United States)) was a significant step forward in improving the diagnosis of TB and the detection of rifampicin resistance globally. However, Xpert MTB/RIF sensitivity is suboptimal, particularly among people (including children) with smear-negative TB and people (including children) living with HIV. The Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, United States), hereafter referred to as Xpert Ultra, was developed by Cepheid as the next-generation assay to overcome these limitations.

Recommendation:

In children with signs and symptoms of pulmonary TB, Xpert Ultra should be used as the initial diagnostic test for TB and detection of rifampicin resistance on sputum, nasopharyngeal aspirate, gastric aspirate or stool, rather than smear microscopy/culture and phenotypic drug susceptibility testing (DST).

Of the estimated 1.1 million children who developed TB annually, only 399 000 (36.5%) were notified to NTPs in 2020. Under-notification is worst among children below 5 years of age, with only 27.5% of children with TB being notified (1). These 'missing' children are not diagnosed and/or not reported. TB-related mortality among children below 15 years of age was estimated at 226 000 for 2020 (1). Modelling has shown that 80% of TB-related deaths are among children under 5 years of age, and that 96% of children who die of TB, did not access treatment (15).

The electronic version of the consolidated guidelines on the management of TB in children and adolescents will form part of the WHO TB KS , which features the following components for each TB module: (i) consolidated guidelines, (ii) operational handbooks with implementation guidance; as well as (iii) a catalogue of WHO e-learning materials.

The 2022 consolidated guidelines represent a significant update compared to the previous guidelines issued in 2014. They include: (i) new recommendations based on the review of newly available evidence related to the Population, Intervention, Comparator and Outcomes (PICO) questions that were developed for this guideline update; (ii) recommendations with relevance to children and adolescents from other WHO TB guidelines issued since 2014; and (iii) a few recommendations from the 2014 guidance that remain unchanged.

The target audience for these consolidated guidelines consists primarily of NTPs, primary health care (PHC) programmes, maternal and child health programmes, national AIDS programmes (or their equivalents in health ministries) and other health policy-makers. They also target generalist and specialist paediatricians, clinicians and health practitioners working on TB, HIV and/or infectious diseases in public and private sectors, the educational sector, nongovernmental, civil society and community-based organizations, as well as technical and implementing partners.

The objectives of the 2022 consolidated guidelines on the management of TB in children and adolescents are to:

Since the publication of the WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children (second edition) (2014) (8),there have been numerous studies, including reviews, randomized controlled trials, observational studies, pharmacokinetic (PK) and pharmacodynamic studies, qualitative research and cost-effectiveness research, which have evaluated the impact of various interventions.