Operational Handbooks

Case detection is a crucial step in the cascade of care for children with TB; however, for most children who die from TB, the disease is never diagnosed (80). Children and adolescents who are younger than 15 years represented approximately 12% of incident cases but 16% of the estimated 1.4 million deaths from TB in 2019 (1). This relatively higher share of mortality in children highlights the urgent need for improved case detection and subsequent access to preventive and curative treatment in this age group, particularly for those at highest risk.

TB remains the primary cause of AIDS-related morbidity and mortality worldwide, despite impressive scale up of antiretroviral treatment (ART). In 2019, TB was associated with an estimated 208 000 (30%) AIDS-related deaths (1). Global estimates show a 44% gap in case detection among people with HIVassociated TB (1). A systematic review of postmortem studies of global AIDS-related deaths in adults found TB to be the primary cause of death in 37.2% of cases (95% CI: 25.7–48.7). TB was undiagnosed prior to death in 45.8% of cases (95% CI: 32.6–59.1) (75).

Countries should position the W4SS, CRP, CXR and mWRD in combination with diagnostic evaluation using mWRDs and LF-LAM (8) within national TB screening and diagnostic algorithms according to their feasibility, the level of the health facility, resources and equity. Algorithms exploring the available screening tools are presented in the operational handbook, including modelled performance of accuracy and yield (7).

Across all populations and tools, more research is needed to evaluate the accuracy and effectiveness of complete screening and diagnostic algorithms, including symptom screening, CXR, CRP and mWRDs used in various combinations with diagnostic evaluation. Research into their effectiveness should include measures of the impacts on patient-important outcomes, such as mortality and treatment success.

For people living with HIV in settings with different TB prevalences, more research is needed to evaluate the accuracy and predictive value of measuring CRP above any cut-off higher than 5 mg/L for TB screening, when it is used either alone or in combination with other screening tests.

1.1 Background

About one fourth of the world’s population is estimated to have been infected with M. tuberculosis (1,2).

This document provides practical guidance on translating WHO’s recommendations for screening into a national or local strategy with clear objectives, prioritization of risk groups and definition of the most appropriate screening approaches.

The specific objectives are:

By reducing cell-mediated immunity, undernutrition increases the risk of TB, while the catabolic effect of TB disease results in weight loss and wasting, creating a vicious cycle (105, 228). Globally, about 45% of deaths in children aged under 5 years are attributable to undernutrition (228). Undernutrition may be acute or chronic and categorized as moderate or severe.

In general, TB medicines should be dosed according to body weight. Dosing of bedaquiline and delamanid for children and young adolescents aged under 15 years was updated in 2021 following an expert consultation meeting convened by WHO. These dosing recommendations are included in Annex 6 and may be updated as evidence emerges, especially for the youngest age groups, for which there is very limited evidence.