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Effect of systematic tuberculosis detection on mortality in young children with severe pneumonia in countries with high incidence of tuberculosis: a stepped-wedge cluster-randomised trial.

Marcy O, Wobudeya E, Font H, Vessière A, Chabala C, Khosa C, Taguebue JV, Moh R, Mwanga-Amumpaire J, Lounnas M, Mulenga V, Mavale S, Chilundo J, Rego D, Nduna B, Shankalala P, Chirwa U, De Lauzanne A, Dim B, Tiogouo Ngouana E, Folquet Amorrissani M, Cisse L, Amon Tanoh Dick F, Komena EA, Kwedi Nolna S, Businge G, Natukunda N, Cumbe S, Mbekeka P, Kim A, Kheang C, Pol S, Maleche-Obimbo E, Seddon JA, Mao TE, Graham SM, Delacourt C, Borand L, Bonnet M, TB-Speed Pneumonia Study Group

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  • Journal The Lancet. Infectious diseases

  • Published 14 Nov 2022

  • Volume 23

  • ISSUE 3

  • Pagination 341-351

  • DOI 10.1016/S1473-3099(22)00668-5

Abstract

Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality.

We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis. Children younger than 5 years with WHO-defined severe pneumonia received either the standard of care (control group) or standard of care plus Xpert MTB/RIF Ultra (Xpert Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal aspirate and stool samples (intervention group). Clusters (hospitals) were progressively switched from control to intervention at 5-week intervals, using a computer-generated random sequence, stratified on incidence rate of tuberculosis at country level, and masked to teams until 5 weeks before switch. We assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. The primary analysis was by intention to treat. We described outcomes in children with severe acute malnutrition in a post hoc analysis. This study is registered with ClinicalTrials.gov (NCT03831906) and the Pan African Clinical Trial Registry (PACTR202101615120643).

less than 90% in 59 (5·2%) children. There was no serious adverse event related to nasopharyngeal aspirates reported during the trial.

Systematic molecular tuberculosis detection at hospital admission did not reduce mortality in children with severe pneumonia. High treatment and microbiological confirmation rates support more systematic use of Xpert Ultra in this group, notably in children with severe acute malnutrition.

Unitaid and L'Initiative.

For the French translation of the abstract see Supplementary Materials section.