A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation.
Children
Molecular diagnostics
PLHIV
Stool
Tuberculosis
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
21 Feb 2024
21 Feb 2024
Historique:
received:
29
09
2023
accepted:
13
10
2023
medline:
22
2
2024
pubmed:
22
2
2024
entrez:
21
2
2024
Statut:
epublish
Résumé
Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed by researchers at Baylor College of Medicine (Houston, Texas, USA) for TB bacteriological confirmation with promising results in pilot studies. The study will take place in high TB/HIV burden countries (Mozambique, Eswatini and Uganda) where we will enroll, over a period of 30 months, 650 PLHIV (> 15) and 1295 children under 8 years of age (irrespective of HIV status) presenting pressumptive TB. At baseline, all participants will provide clinical history, complete a physical assessment, and undergo thoracic chest X-ray imaging. To obtain bacteriological confirmation, participants will provide respiratory samples (1 for adults, 2 in children) and 1 stool sample for Xpert Ultra MTB/RIF (Cepheid, Sunnyvale, CA, USA). Mycobacterium tuberculosis (M.tb) liquid culture will only be performed in respiratory samples and lateral flow lipoarabinomannan (LF-LAM) in urine following WHO recommendations. Participants will complete 2 months follow-up if they are not diagnosed with TB, and 6 months if they are. For analytical purposes, the participants in the pediatric cohort will be classified into "confirmed tuberculosis", "unconfirmed tuberculosis" and "unlikely tuberculosis". Participants of the adult cohort will be classified as "bacteriologically confirmed TB", "clinically diagnosed TB" or "not TB". We will assess accuracy of the novel qPCR test compared to bacteriological confirmation and Tb diagnosis irrespective of laboratory results. Longitudinal qPCR results will be analyzed to assess its use as treatment response monitoring. The proposed stool-based qPCR is an innovation because both the strategy of using a non-sputum based sample and a technique specially designed to detect M.tb DNA in stool. ClinicalTrials.gov Identifier: NCT05047315.
Sections du résumé
BACKGROUND
BACKGROUND
Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed by researchers at Baylor College of Medicine (Houston, Texas, USA) for TB bacteriological confirmation with promising results in pilot studies.
METHODS
METHODS
The study will take place in high TB/HIV burden countries (Mozambique, Eswatini and Uganda) where we will enroll, over a period of 30 months, 650 PLHIV (> 15) and 1295 children under 8 years of age (irrespective of HIV status) presenting pressumptive TB. At baseline, all participants will provide clinical history, complete a physical assessment, and undergo thoracic chest X-ray imaging. To obtain bacteriological confirmation, participants will provide respiratory samples (1 for adults, 2 in children) and 1 stool sample for Xpert Ultra MTB/RIF (Cepheid, Sunnyvale, CA, USA). Mycobacterium tuberculosis (M.tb) liquid culture will only be performed in respiratory samples and lateral flow lipoarabinomannan (LF-LAM) in urine following WHO recommendations. Participants will complete 2 months follow-up if they are not diagnosed with TB, and 6 months if they are. For analytical purposes, the participants in the pediatric cohort will be classified into "confirmed tuberculosis", "unconfirmed tuberculosis" and "unlikely tuberculosis". Participants of the adult cohort will be classified as "bacteriologically confirmed TB", "clinically diagnosed TB" or "not TB". We will assess accuracy of the novel qPCR test compared to bacteriological confirmation and Tb diagnosis irrespective of laboratory results. Longitudinal qPCR results will be analyzed to assess its use as treatment response monitoring.
DISCUSSION
CONCLUSIONS
The proposed stool-based qPCR is an innovation because both the strategy of using a non-sputum based sample and a technique specially designed to detect M.tb DNA in stool.
PROTOCOL REGISTRATION DETAILS
UNASSIGNED
ClinicalTrials.gov Identifier: NCT05047315.
Identifiants
pubmed: 38383310
doi: 10.1186/s12879-023-08708-9
pii: 10.1186/s12879-023-08708-9
doi:
Banques de données
ClinicalTrials.gov
['NCT05047315']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
233Subventions
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : European and Developing Countries Clinical Trials Partnership
ID : EDCTP Grant RIA2018D-2511
Organisme : Horizon 2020 Framework Programme
ID : Marie Sklodowska Curie Grant n. 847462
Investigateurs
Sergi Sanz
(S)
Makhosazana Dlamini
(M)
Gcinile Dlamini
(G)
Nomathemba Dlamini
(N)
Nkulungwane Mthethwa
(N)
Nokwanda Kota
(N)
Mbongeni Dube
(M)
Nontobeko Maphalala
(N)
Babongile Nkala
(B)
Faith Dlamini
(F)
Fortunate Shabalala
(F)
Sindisiwe Dlamini
(S)
Gugu Maphalala
(G)
Lindiwe Dlamini
(L)
Sisi Dube
(S)
Lee Joao Fonseca
(LJ)
Nércio Machele
(N)
Miguel Cumbe
(M)
Agostinho Lima
(A)
Katia Magul
(K)
Gustavo Tembe
(G)
Benilde Violeta Mudumane
(BV)
Farida Cebola
(F)
Jorcelina Rungo
(J)
Alberto Bila Junior
(A)
Neide Gomes
(N)
Patricia Mwachan
(P)
Maria Nassolo
(M)
Sujan Katuwal
(S)
Matthew Ang
(M)
Anca Vasiliu
(A)
Rojelio Mejía
(R)
Jason Bacha
(J)
Debrah Vambe
(D)
Abigail Seeger
(A)
Irina Kontsevaya
(I)
Collins Musia
(C)
Lilian Komba
(L)
Lwijisyo Minga
(L)
Lumumba Mwita
(L)
Mtafya Bariki
(M)
Nyanda Elias Ntinginya
(NE)
Informations de copyright
© 2024. The Author(s).
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