Development of tuberculosis treatment decision algorithms in children below 5 years hospitalised with severe acute malnutrition in Zambia and Uganda: a prospective diagnostic cohort studyResearch in context

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...

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Published in:	EClinicalMedicine Vol. 73; p. 102688
Main Authors:	Chishala Chabala, Clémentine Roucher, Minh Huyen Ton Nu Nguyet, Esther Babirekere, Muleya Inambao, Gerald Businge, Chifunda Kapula, Perfect Shankalala, Bwendo Nduna, Veronica Mulenga, Stephen Graham, Eric Wobudeya, Maryline Bonnet, Olivier Marcy, Angeline Serre, Anne Badrichani, Manoa Razafimanantsoa, Julien Poublan, Aurélia Vessière, Estelle Occelli, Aurélie Beuscart, Aurélie Charpin, Gemma Habiyambere, Salomé Mesnier, Eric Balestre, Nicolas Koskas, Marc D'Elbée, Hélène Font, Manon Lounnas, Hélène Espérou, Sandrine Couffin-Cadiergues, Alexis Kuppers, Benjamin Hamze, Gerald Bright Businge, Faith Namulinda, Robert Sserunjogi, Rashidah Nassozi, Charlotte Barungi, Aanyu Hellen, Muwonge Doreen, Eva Kagoya, Serene Aciparu, Chemutai Sophia, Samuel Ntambi, Amir Wasswa, Juliet Nangozi, Chimuka Hambulo, Vincent Kapotwe, Marjory Ngambi, Kunda Kasakwa, Mirriam Kanyama, Uzima Chirwa, Kapula Chifunda, Gae Mundundu, Susan Zulu, Grace Nawakwi, Teddy Siasulingana, Diana Attan Himwaze, Jessy Chilonga, Maria Chimbini, Mutinta Chilanga, Daniel Chola, Eustace Mwango, Mwamba Pumbwe, Mwate Mwambazi, Barbara Halende, Wyclef Mumba, Endreen Mankunshe, Maureen Silavwe, Moses Chakopo, Roy Moono, Chalilwe Chungu, Kevin Zimba, Monica Kapasa, Khozya Zyambo
Format:	Journal Article
Language:	English
Published:	Elsevier 01-07-2024
Subjects:	Children Diagnosis Severe acute malnutrition Treatment decision algorithms Tuberculosis
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Summary:	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.
ISSN:	2589-5370