RESUMO
Background: In children with severe acute malnutrition (SAM) tuberculosis is common, challenging to diagnose, and often fatal. We developed tuberculosis treatment decision algorithms (TDAs) for children under the age of 5 years with SAM. Methods: In this prospective diagnostic study, we enrolled and followed up children aged <60 months hospitalised with SAM at three tertiary hospitals in Zambia and Uganda from 4 November 2019 to 20 June 2022. We included children aged 2-59 months with SAM as defined by WHO and hospitalised following the WHO clinical criteria. We excluded children with current or history of antituberculosis treatment within the preceding 3 months. They underwent tuberculosis symptom screening, clinical assessment, chest X-ray, abdominal ultrasound, Xpert MTB/RIF Ultra (Ultra) and culture on respiratory and stool samples with 6 months follow-up. Tuberculosis was retrospectively defined using the 2015 standard case definition for childhood tuberculosis. We used logistic regression to develop diagnostic prediction models for a one-step diagnosis and a two-step screening and diagnostic approaches. We derived scores from models using WHO-recommended thresholds for sensitivity and proposed TDAs. This study is registered with ClinicalTrials.gov, NCT04240990. Findings: Of 1906 children hospitalised with SAM during the study period, 1230 were screened, 1152 were eligible and 603 were enrolled. Of the 603 children enrolled-median age 15 (inter-quartile range (IQR): 11-20) months and 65 (11.0%) living with HIV-114 (18.9%) were diagnosed with tuberculosis, including 51 (8.5%) with microbiological confirmation and 104 (17.2%) initiated treatment at a median of 6(IQR: 2-10) days after inclusion. 108 children were retrospectively classified as having tuberculosis resulting in a prevalence of 17.9% (95% confidence intervals (CI): 15.1; 21.2). 75 (69.4%) children with tuberculosis reported cough of any duration, 32 (29.6%) cough ≥2 weeks and 11 (10.2%) tuberculosis contact history. 535 children had complete data and were included in the diagnostic prediction model. The one-step diagnostic model had 15 predictors, including Ultra, clinical, radiographic, and abdominal features, an area under the receiving operating curve (AUROC) of 0.910, and derived TDA sensitivity of 86.14% (95% CI: 78.07-91.56) and specificity of 80.88% (95% CI: 76.91-84.30). The two-step model had AUROCs of 0.750 and 0.912 for screening and diagnosis, respectively, and derived combined TDA sensitivity of 79.21% (95% CI: 70.30-85.98) and a specificity of 83.64% (95% CI: 79.87-86.82). Interpretation: Tuberculosis prevalence was high among hospitalised children with SAM, with atypical clinical features. TDAs achieved satisfactory diagnostic accuracy and could be used to improve diagnosis in this vulnerable group. Funding: Unitaid.
RESUMO
Background: Childhood tuberculosis (TB) remains underdiagnosed largely because of limited awareness and poor access to all or any of specimen collection, molecular testing, clinical evaluation, and chest radiography at low levels of care. Decentralising childhood TB diagnostics to district hospitals (DH) and primary health centres (PHC) could improve case detection. Methods: We conducted an operational research study using a pre-post intervention cross-sectional study design in 12 DHs and 47 PHCs of 12 districts across Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included 1) a comprehensive diagnosis package at patient-level with tuberculosis screening for all sick children and young adolescents <15 years, and clinical evaluation, Xpert Ultra-testing on respiratory and stool samples, and chest radiography for children with presumptive TB, and 2) two decentralisation approaches (PHC-focused or DH-focused) to which districts were randomly allocated at country level. We collected aggregated and individual data. We compared the proportion of tuberculosis detection in children and young adolescents <15 years pre-intervention (01 August 2018-30 November 2019) versus during intervention (07 March 2020-30 September 2021), overall and by decentralisation approach. This study is registered with ClinicalTrials.gov, NCT04038632. Findings: TB was diagnosed in 217/255,512 (0.08%) children and young adolescent <15 years attending care pre-intervention versus 411/179,581 (0.23%) during intervention, (OR: 3.59 [95% CI 1.99-6.46], p-value<0.0001; p-value = 0.055 after correcting for over-dispersion). In DH-focused districts, TB diagnosis was 80/122,570 (0.07%) versus 302/86,186 (0.35%) (OR: 4.07 [1.86-8.90]; p-value = 0.0005; p-value = 0.12 after correcting for over-dispersion); and 137/132,942 (0.10%) versus 109/93,395 (0.11%) in PHC-focused districts, respectively (OR: 2.92 [1.25-6.81; p-value = 0.013; p-value = 0.26 after correcting for over-dispersion). Interpretation: Decentralising and strengthening childhood TB diagnosis at lower levels of care increases tuberculosis case detection but the difference was not statistically significant. Funding source: Unitaid, Grant number 2017-15-UBx-TB-SPEED.