Background Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)‐recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents. Objectives To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021. Selection criteria Cross‐sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV‐positive and HIV‐negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDR plus . Data collection and analysis Two review authors independently extracted data and, using QUADAS‐2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tubercul...

Increasing attention is being given to the challenges of management and prevention of tuberculosis in children and adolescents. There have been a number of recent important milestones achieved at the global level to address this previously neglected disease. There is now a need to increase activities and build partnerships at the regional and national levels in order to address the wide policy-practice gaps for implementation, and to take the key steps outlined in the Roadmap for Child Tuberculosis published in 2013. In this article, we provide the rationale and suggest strategies illustrated with examples to improve diagnosis, management, outcomes and prevention for children with tuberculosis in the Asia-Pacific region, with an emphasis on the need for greatly improved recording and reporting. Effective collaboration with community engagement between the child health sector, the National Tuberculosis control Programmes, community-based services and the communities themselves are essential.

Background: Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown. Methods: To inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of six- to less than 12-months’ duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes. Results: Of seven included studies, none compared regimens head-to-head. Three studies (724 patients) used a six-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this vs. the 12-month regimen (282 patients, three studies) were respectively: death, 5.5% (95% CI: 2.1-13.4%) vs. 23.9% (95% CI: 17.5-31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI: 73.9-99.1%) vs. 75.4% (95% CI: 68.7-81.1%); and neurological sequelae among survivors, 66.0% (95% CI: 55.3-75.3%) vs. 36.3% (95% CI: 30.1-43.0%). Relapse did not occur among 148 patients followed-up for two years after completing the six-month intensive regimen. Conclusions: Our findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.

The burden of tuberculosis (TB) among children and young adolescents (<15 years old) is estimated at 1.1 million; however, only 400,000 are treated for TB, indicating a large gap between the number who are cared for and the number estimated to have TB. Accurate data on the burden of pediatric TB is essential to guide action. Despite several improvements in estimating the burden of pediatric TB in the last decade, as well as enhanced data collection efforts, several data gaps remain, both at the global level, but also at the national level where surveillance systems and collaborative research are critical. In this article, we describe recent advances in data collection and burden estimates for TB among children and adolescents, and the remaining gaps. While data collection continues to improve, burden estimates must evolve in parallel, both in terms of their frequency and the methods used. Currently, at the global level, there is a focus on age-disaggregation of TB notifications, the collection of data on TB-HIV, multi-drug resistant (MDR)-TB and treatment outcomes, as well as estimates of the disease burden. Additional data from national surveillance systems or research projects on TB meningitis, as well as other forms of extra-pulmonary TB, would be useful. We must capitalize on the current momentum in child and adolescent TB to close the remaining data gaps for these age groups to better understand the epidemic and further reduce morbidity and mortality due to TB.

Objective To map which tuberculosis care models are best suited for children and adolescents. Methods We conducted a scoping review to assess the impact of decentralized, integrated and family-centred care on child and adolescent tuberculosis-related outcomes, describe approaches for these care models and identify key knowledge gaps. We searched seven literature databases on 5 February 2021 (updated 16 February 2022), searched the references of 18 published reviews and requested data from ongoing studies. We included studies from countries with a high tuberculosis burden that used a care model of interest and reported tuberculosis diagnostic, treatment or prevention outcomes for an age group < 20 years old. Findings We identified 28 studies with a comparator group for the impact assessment and added 19 non-comparative studies to a qualitative analysis of care delivery approaches. Approaches included strengthening capacity in primary-level facilities, providing services in communities, screening for tuberculosis in other health services, co-locating tuberculosis and human immunodeficiency virus treatment, offering a choice of treatment location and providing social or economic support. Strengthening both decentralized diagnostic services and community linkages led to one-to-sevenfold increases in case detection across nine studies and improved prevention outcomes. We identified only five comparative studies on integrated or family-centred care, but 11 non-comparative studies reported successful treatment outcomes for at least 71% of children and adolescents. Conclusion Strengthening decentralized services in facilities and communities can improve tuberculosis outcomes for children and adolescents. Further research is needed to identify optimal integrated and family-centred care approaches.