Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial
Aurelia Vessiere
(1)
,
Helene Font
(1)
,
Delphine Gabillard
(1)
,
Laurence Adonis-Koffi
,
Laurence Borand
,
Chishala Chabala
(2)
,
Celso Khosa
(3)
,
Sandra Mavale
(3)
,
Raoul Moh
(4)
,
Veronica Mulenga
(2)
,
Juliet Mwanga-Amumpere
(5)
,
Jean-Voisin Taguebue
(5)
,
Mao Tan Eang
(6)
,
Christophe Delacourt
(7)
,
James A. Seddon
(8, 9)
,
Manon Lounnas
(10, 11)
,
Sylvain Godreuil
(10, 11)
,
Eric Wobudeya
(12)
,
Maryline Bonnet
(10, 13)
,
Olivier Marcy
(1)
1
BPH -
Bordeaux population health
2 UNZA - University of Zambia [Lusaka]
3 Maputo Central Hospital
4 CHU - Centre Hospitalier Universitaire [Treichville]
5 Epicentre Ouganda [Mbarara] [Médecins Sans Frontières]
6 CENAT - National Center for Tuberculosis and Leprosy Control [Phnom Penh, Cambodia]
7 Hôpital Necker - Enfants Malades [AP-HP]
8 Stellenbosch University
9 Imperial College London
10 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
11 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
12 Bugema University [Kampala]
13 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
2 UNZA - University of Zambia [Lusaka]
3 Maputo Central Hospital
4 CHU - Centre Hospitalier Universitaire [Treichville]
5 Epicentre Ouganda [Mbarara] [Médecins Sans Frontières]
6 CENAT - National Center for Tuberculosis and Leprosy Control [Phnom Penh, Cambodia]
7 Hôpital Necker - Enfants Malades [AP-HP]
8 Stellenbosch University
9 Imperial College London
10 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
11 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
12 Bugema University [Kampala]
13 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
Laurence Adonis-Koffi
- Fonction : Auteur
Laurence Borand
- Fonction : Auteur
- PersonId : 763094
- ORCID : 0000-0001-7431-5900
Christophe Delacourt
- Fonction : Auteur
- PersonId : 930574
- ORCID : 0000-0002-0007-7150
- IdRef : 034511717
Manon Lounnas
- Fonction : Auteur
- PersonId : 1358375
- IdHAL : manon-lounnas
- ORCID : 0000-0001-8789-0517
Résumé
Background: In high tuberculosis (TB) burden settings, there is growing evidence that TB is common in children with pneumonia, the leading cause of death in children under 5 years worldwide. The current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. As a result, many children with TB-associated severe pneumonia are currently missed or diagnosed too late. We therefore propose a diagnostic trial to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stool samples to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. Methods: TB-Speed Pneumonia is a pragmatic stepped-wedge cluster randomized controlled trial conducted in six countries with high TB incidence rate (Côte d’Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia). We will enrol 3780 children under 5 years presenting with WHO-defined severe pneumonia across 15 hospitals over 18 months. All hospitals will start managing children using the WHO SOC for severe pneumonia; one hospital will be randomly selected to switch to the intervention every 5 weeks. The intervention consists of the WHO SOC plus rapid TB detection on the day of admission using Ultra performed on 1 nasopharyngeal aspirate and 1 stool sample. All children will be followed for 3 months, with systematic trial visits at day 3, discharge, 2 weeks post-discharge, and week 12. The primary endpoint is all-cause mortality 12 weeks after inclusion. Qualitative and health economic evaluations are embedded in the trial. Discussion: In addition to testing the main hypothesis that molecular detection and early treatment will reduce TB mortality in children, the strength of such pragmatic research is that it provides some evidence regarding the feasibility of the intervention as part of routine care. Should this intervention be successful, safe and well tolerated, it could be systematically implemented at district hospital level where children with severe pneumonia are referred. Trial registration: ClinicalTrials.gov, NCT03831906 . Registered 6 February 2019.
Domaines
Santé publique et épidémiologieFormat du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial
|
Résumé |
en
Background: In high tuberculosis (TB) burden settings, there is growing evidence that TB is common in children with pneumonia, the leading cause of death in children under 5 years worldwide. The current WHO standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. As a result, many children with TB-associated severe pneumonia are currently missed or diagnosed too late. We therefore propose a diagnostic trial to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stool samples to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples. Methods: TB-Speed Pneumonia is a pragmatic stepped-wedge cluster randomized controlled trial conducted in six countries with high TB incidence rate (Côte d’Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia). We will enrol 3780 children under 5 years presenting with WHO-defined severe pneumonia across 15 hospitals over 18 months. All hospitals will start managing children using the WHO SOC for severe pneumonia; one hospital will be randomly selected to switch to the intervention every 5 weeks. The intervention consists of the WHO SOC plus rapid TB detection on the day of admission using Ultra performed on 1 nasopharyngeal aspirate and 1 stool sample. All children will be followed for 3 months, with systematic trial visits at day 3, discharge, 2 weeks post-discharge, and week 12. The primary endpoint is all-cause mortality 12 weeks after inclusion. Qualitative and health economic evaluations are embedded in the trial. Discussion: In addition to testing the main hypothesis that molecular detection and early treatment will reduce TB mortality in children, the strength of such pragmatic research is that it provides some evidence regarding the feasibility of the intervention as part of routine care. Should this intervention be successful, safe and well tolerated, it could be systematically implemented at district hospital level where children with severe pneumonia are referred. Trial registration: ClinicalTrials.gov, NCT03831906 . Registered 6 February 2019.
|
Auteur(s) |
Aurelia Vessiere
1
, Helene Font
1
, Delphine Gabillard
1
, Laurence Adonis-Koffi
, Laurence Borand
, Chishala Chabala
2
, Celso Khosa
3
, Sandra Mavale
3
, Raoul Moh
4
, Veronica Mulenga
2
, Juliet Mwanga-Amumpere
5
, Jean-Voisin Taguebue
5
, Mao Tan Eang
6
, Christophe Delacourt
7
, James A. Seddon
8, 9
, Manon Lounnas
10, 11
, Sylvain Godreuil
10, 11
, Eric Wobudeya
12
, Maryline Bonnet
10, 13
, Olivier Marcy
1
1
BPH -
Bordeaux population health
( 476572 )
- Université de Bordeaux - Case 11 - 146 rue Léo Saignat 33076 Bordeaux cedex
- France
2
UNZA -
University of Zambia [Lusaka]
( 563773 )
- Zambie
3
Maputo Central Hospital
( 455779 )
- Maputo
- Mozambique
4
CHU -
Centre Hospitalier Universitaire [Treichville]
( 357686 )
- Côte d’Ivoire
5
Epicentre Ouganda [Mbarara] [Médecins Sans Frontières]
( 356833 )
- P.O Box 1956, Mbarara
- Ouganda
6
CENAT -
National Center for Tuberculosis and Leprosy Control [Phnom Penh, Cambodia]
( 1072456 )
- Street 278/288/95, Sangkat Boeng Keng Kang 2, Khane Chamkamonn, Phnom Penh
- Cambodge
7
Hôpital Necker - Enfants Malades [AP-HP]
( 414766 )
- 149 Rue de Sèvres 75015 Paris
- France
8
Stellenbosch University
( 302530 )
- Stellenbosch University
Private Bag X1,
Matieland, 7602,
Stellenbosch, South Africa
- Afrique du Sud
9
Imperial College London
( 69530 )
- South Kensington Campus, London SW7 2AZ
- Royaume-Uni
10
CHRU Montpellier -
Centre Hospitalier Régional Universitaire [Montpellier]
( 258773 )
- 191 avenue du doyen Gaston Giraud 34295 Montpellier
- France
11
MIVEGEC -
Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
( 166573 )
- 911 Avenue Agropolis BP 64501 34394 Montpellier cedex 5
- France
12
Bugema University [Kampala]
( 569195 )
- Ouganda
13
TransVIHMI -
Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
( 1087128 )
- Centre IRD France Sud 911, avenue Agropolis BP 64501 F-34394 Montpellier cedex 5
- France
|
Licence |
Paternité
|
Langue du document |
Anglais
|
Nom de la revue |
|
Comité de lecture |
Oui
|
Date de publication |
2021-03-20
|
Volume |
21
|
Numéro |
1
|
Page/Identifiant |
136
|
Vulgarisation |
Non
|
Audience |
Internationale
|
Domaine(s) |
|
Mots-clés |
en
Children, Pneumonia, Tuberculosis, Nasopharyngeal aspirate, Stool, Xpert MTB/RIF ultra
|
DOI | 10.1186/s12887-021-02576-5 |
Pubmed Id | 33743621 |
PubMed Central | PMC7980598 |
UT key WOS | 000630859900001 |
Origine :
Publication financée par une institution
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