Young children are most vulnerable to develop severe forms of tuberculosis (TB) and are over-represented among TB deaths. Almost all children estimated to have died from TB were never diagnosed or offered TB treatment. Improved access to TB preventive treatment (TPT) requires major upscaling of household contact investigation with allocation of adequate resources. Symptom-based screening is often discouraged in adults for fear of generating drug resistance, if TB cases are missed. However, the situation in vulnerable young children is different, as they present minimal risk of drug resistance generation. Further, the perceived need for additional diagnostic evaluation presents a major barrier to TPT access and underlies general reluctance to consider pragmatic decentralised models of care. Widespread roll-out of Xpert MTB/RIF Ultra® represents an opportunity for improved case detection in young children, but attaining full impact will require the use of non-sputum specimens. The new Fujifilm SILVAMP TB LAM® urine assay demonstrated good diagnostic accuracy in HIV-positive and malnourished children, but further validation is required. Given the limited accuracy of all available tests and the excellent tolerance of TB drugs in children, the global community may have to accept some over-treatment if we want to close the persistent case detection gap in young children.

There were approximately 10 million tuberculosis (TB) cases in 2020, of which 500,000 were drug-resistant. Only one third of drug-resistant TB cases were diagnosed and enrolled on appropriate treatment, an issue partly driven by a lack of rapid, accurate drug-susceptibility testing (DST) tools deployable in peripheral settings. In 2014, World Health Organization (WHO) published target product profiles (TPPs) which detailed minimal and optimal criteria to address high-priority TB diagnostic needs, including DST. Since then, the TB community’s needs have evolved; new treatment regimens, changes in TB definitions, further emergence of drug resistance, technological advances, and changing end-users requirements have necessitated an update. The DST TPP’s revision was therefore undertaken by WHO with the Stop TB Partnership New Diagnostics Working Group. We describe the process of updating the TPP for next-generation TB DST for use at peripheral centres, highlight key updates, and discuss guidance regarding technical and operational specifications.

The 2021 Global Tuberculosis (TB) report shows slow progress towards closing the pediatric TB detection gap and improving the TB preventive treatment (TPT) coverage among child and adolescent contacts. This review presents the current knowledge around contact case management (CCM) in low-resource settings, with a focus on child contacts, which represents a key priority population for CCM and TPT. Compelling evidence demonstrates that CCM interventions are a key gateway for both TB case finding and identification of those in need of TPT, and their yield and effectiveness should provide a strong rationale for prioritization by national TB programs. A growing body of evidence is now showing that innovative models of care focused on community-based and patient-centered approaches to household contact investigation can help narrow down the CCM implementation gaps that we are currently facing. The availability of shorter and child-friendly TPT regimens for child contacts provide an additional important opportunity to improve TPT acceptability and adherence. Prioritization of TB CCM implementation and adequate resource mobilization by ministries of health, donors and implementing agencies is needed to timely close the gap.

Introduction: Paediatric tuberculosis (TB) underdiagnosis is a critical concern. The INPUT stepped-wedge cluster-randomised trial assessed the impact of integrating child TB services into child healthcare on TB case detection among children under age 5 years. Methods: We compared the standard of care, providing TB care in specific TB clinics (control phase), with the Catalysing Paediatric TB Innovations (CaP-TB) intervention, integrating TB services across all child health services (intervention phase). 12 clusters in Cameroon and Kenya transitioned from the standard of care to the intervention at randomly assigned times. Children with presumptive TB were enrolled after obtaining their parents’ consent and were followed throughout TB diagnostic procedures and treatment. Study outcomes included the rate of children with presumptive TB receiving TB investigations and that of children diagnosed with TB (the primary outcome was case detection), per thousand children under 5 years attending facilities. Generalised linear mixed Poisson models estimated the intervention’s effect as adjusted rate ratios (aRR) and associated 95% CIs. Ad hoc country-stratified analyses were conducted. Results: During control and intervention phases, respectively, 121 909 and 109 614 children under 5 years attended paediatric entry points, 133 (1.1 per thousand) and 610 (5.6 per thousand) children with presumptive TB received TB investigations, and 79 and 74 were diagnosed with TB, corresponding to a case detection rate of 0.64 and 0.68 per thousand, respectively. CaP-TB significantly increased TB investigations in both countries overall (aRR=3.9, 95% CI 2.4 to 5.4), and in each. Overall, TB case detection was not statistically different between intervention and control (aRR 1.32, 95% CI 0.66 to 2.61, p=0.43). Country-stratified analysis revealed a 10-fold increase (aRR 9.75, 95% CI 1.04 to 91.84, p=0.046) in case detection with CaP-TB in Cameroon and no significant effect in Kenya (aRR 0.94, 95% CI 0.44 to 2.01, p=0.88). Conclusion: CaP-TB increased TB investigations in both study countries and markedly enhanced TB case detection in one, underlining integrated TB services' potential to address paediatric TB underdiagnosis.

In 2022, an estimated 1.25 million children 50% remained undiagnosed or unreported. WHO recently recommended integrated and decentralized models of care as an approach to improve access to TB services for children, but evidence remains limited. The Catalyzing Paediatric TB Innovation project (CaP-TB) implemented a multi-pronged intervention to improve TB case finding in children in nine sub-Saharan African countries. The intervention introduced systematic TB screening in different facility-based child-health entry-points, decentralisation of TB diagnosis and management, improved sample collection with access to Xpert^® MTB/RIF or MTB/RIF Ultra testing, and implementation of contact investigation. Pre-intervention records were compared with those during intervention to assess effect on paediatric TB cascade of care. The intervention screened 1 991 401 children <15 years of age for TB across 144 health care facilities. The monthly paediatric TB case detection rate increased significantly during intervention versus pre-intervention (+46.0%, 95% CI 36.2–55.8%; p<0.0001), with variability across countries. The increase was greater in the <5 years old compared to the 5–14 years old (+53.4%, 95% CI 35.2–71.9%; p<0.0001 versus +39.9%, 95% CI 27.6–52.2%; p<0.0001). Relative contribution of lower-tier facilities to total case detection rate increased from 37% (71.8/191.8) pre-intervention to 50% (139.9/280.2) during intervention. The majority (89.5%) of children with TB were identified through facility-based intensified case-finding and primarily accessed care through outpatient and inpatient departments. In this multi-country study implemented under real-life conditions, the implementation of integrated and decentralized interventions increased paediatric TB case detection. The increase was driven by lower-tier facilities that serve as the primary point of healthcare contact for most patients. The effect was greater in children < 5 years compared to 5–14 years old, representing an important achievement as the TB detection gap is higher in this subpopulation. (Study number NCT03948698)

Background: In 2021, over one million children developed tuberculosis, resulting in 214 000 deaths, largely due to inadequate diagnosis and treatment. The diagnosis and treatment of tuberculosis is limited in most high-burden countries because services are highly centralised at secondary/tertiary levels and are managed in a vertical, non-integrated way. To improve case detection and treatment among children, the World Health Organisation (WHO) recommends decentralised and integrated tuberculosis care models. The Integrating Paediatric TB Services Into Child Healthcare Services in Africa (INPUT) stepped-wedge cluster-randomised trial evaluated the impact of integrating tuberculosis services into healthcare for children under five in Cameroon and Kenya, compared with usual care, finding a 10-fold increase in tuberculosis case detection in Cameroon but no effect in Kenya. Methods: We estimated intervention impact on healthcare outcomes, resource use, health system costs and cost-effectiveness relative to the standard of care (SoC) using a decision tree analytical approach and data from the INPUT trial. INPUT trial data on cascades, resource use and intervention diagnostic rate ratios were used to parametrise the decision tree model. Health outcomes following tuberculosis treatment were modelled in terms of mortality and disability-adjusted life-years (DALYs). Findings: For every 100 children starting antituberculosis treatment under SoC, an additional 876 (95% uncertainty interval (UI) −76 to 5518) in Cameroon and −6 (95% UI −61 to 96) in Kenya would start treatment under the intervention. Treatment success would increase by 5% in Cameroon and 9% in Kenya under the intervention compared with SoC. An estimated 350 (95% UI −31 to 2204) and 3 (95% UI −22 to 48) deaths would be prevented in Cameroon and Kenya, respectively. The incremental cost-effectiveness ratio for the intervention compared with SoC was US$506 and US$1299 per DALY averted in Cameroon and Kenya, respectively. Interpretation: Although likely to be effective, the cost-effectiveness of integrating tuberculosis services into child healthcare services depends on baseline service coverage, tuberculosis detection and treatment outcomes.