@article{fdi:010087516,
  title = {{E}ffect 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},
  author = {{M}arcy, {O}livier and {W}obudeya, {E}. and {F}ont, {H}. and {V}essiere, {A}. and {C}habala, {C}. and {K}hosa, {C}. and {T}aguebue, {J}. {V}. and {M}oh, {R}. and {M}wanga-{A}mumpaire, {J}. and {L}ounnas, {M}anon and {M}ulenga, {V}. and {M}avale, {S}. and {C}hilundo, {J}. and {R}ego, {D}. and {N}duna, {B}. and {S}hankalala, {P}. and {C}hirwa, {U}. and {D}e {L}auzanne, {A}. and {D}im, {B}. and {N}gouana, {E}. {T}. and {A}morrissani, {M}. {F}. and {C}isse, {L}. and {D}ick, {F}. {A}. {T}. and {K}omena, {E}. {A}. and {N}olna, {S}. {K}. and {B}usinge, {G}. and {N}atukunda, {N}. and {C}umbe, {S}. and {M}bekeka, {P}. and {K}im, {A}. and {K}heang, {C}. and {P}ol, {S}. and {M}aleche-{O}bimbo, {E}. and {S}eddon, {J}. {A}. and {M}ao, {T}. {E}. and {G}raham, {S}. {M}. and {D}elacourt, {C}. and {B}orand, {L}. and {B}onnet, {M}aryline},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {T}uberculosis 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. {S}ystematic tuberculosis detection at hospital admission could increase case detection and reduce mortality. {M}ethods {W}e did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries ({C}ambodia, {C}ameroon, {C}ote d'{I}voire, {M}ozambique, {U}ganda, and {Z}ambia) with high incidence of tuberculosis. {C}hildren younger than 5 years with {WHO}-defined severe pneumonia received either the standard of care (control group) or standard of care plus {X}pert {MTB}/{RIF} {U}ltra ({X}pert {U}ltra; {C}epheid, {S}unnyvale, {CA}, {USA}) on nasopharyngeal aspirate and stool samples (intervention group). {C}lusters (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. {W}e assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. {T}he primary analysis was by intention to treat. {W}e described outcomes in children with severe acute malnutrition in a post hoc analysis. {T}his study is registered with {C}linical{T}rials.gov ({NCT}03831906) and the {P}an {A}frican {C}linical {T}rial {R}egistry ({PACTR}202101615120643). {F}indings {F}rom {M}arch 21, 2019, to {M}arch 30, 2021, we enrolled 1401 children in the control group and 1169 children in the intervention group. {I}n the intervention group, 1140 (97.5%) children had nasopharyngeal aspirates and 942 (80.6%) had their stool collected; 24 (2.1%) had positive {X}pert {U}ltra. {A}t 12 weeks, 110 (7.9%) children in the control group and 91 (7.8%) children in the intervention group had died (adjusted odds ratio [{OR}] 0.986, 95% {CI} 0.597-1.630, p=0.957), and 74 (5.3%) children in the control group and 88 (7.5%) children in the intervention group had tuberculosis diagnosed (adjusted {OR} 1.238, 95% {CI} 0.696-2.202, p=0.467). {I}n children with severe acute malnutrition, 57 (23.8%) of 240 children in the control group and 53 (17.8%) of 297 children in the intervention group died, and 36 (15.0%) of 240 children in the control group and 56 (18.9%) of 297 children in the intervention group were diagnosed with tuberculosis. {T}he main adverse events associated with nasopharyngeal aspirates were samples with blood in 312 (27.3%) of 1147 children with nasopharyngeal aspirates attempted, dyspnoea or {S}p{O}2 less than 95% in 134 (11.4%) of children, and transient respiratory distress or {S}p{O}2 less than 90% in 59 (5.2%) children. {T}here was no serious adverse event related to nasopharyngeal aspirates reported during the trial. {I}nterpretation {S}ystematic molecular tuberculosis detection at hospital admission did not reduce mortality in children with severe pneumonia. {H}igh treatment and microbiological confirmation rates support more systematic use of {X}pert {U}ltra in this group, notably in children with severe acute malnutrition.},
  keywords = {{CAMBODGE} ; {CAMEROUN} ; {COTE} {D}'{IVOIRE} ; {MOZAMBIQUE} ; {OUGANDA} ; {ZAMBIE}},
  booktitle = {},
  journal = {{L}ancet {I}nfectious {D}iseases},
  volume = {23},
  numero = {3},
  pages = {341--351},
  ISSN = {1473-3099},
  year = {2023},
  DOI = {10.1016/s1473-3099(22)00668-5},
  URL = {https://www.documentation.ird.fr/hor/fdi:010087516},
}