Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar

Emmanuelle Sandra Adjoa Ametepe; Noela Andriamanoha; Fanantenana Randria Andrianomanana; Floriane Point; Reziky Tiandraza Mangahasimbola; Alina Dyachenko; Michael Hall; Theodora Mayouya Gamana; Astrid M. Knoblauch; Yemimah Yededyah Razafindrasoa; Arianminpathy Nimalan; Marcel Behr; Madeleine Durand; Mira Johri; Zamin Iqbal; Andry Rivo Rakotoarivelo; Rindra Vatosoa Randremanana; Niaina Rakotosamimanana; Simon Grandjean Lapierre

doi:10.1186/s13063-024-08537-4

Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar

Emmanuelle Sandra Adjoa Ametepe, Noela Andriamanoha, Fanantenana Randria Andrianomanana, Floriane Point, Reziky Tiandraza Mangahasimbola, Alina Dyachenko, Michael Hall, Theodora Mayouya Gamana, Astrid M. Knoblauch, Yemimah Yededyah Razafindrasoa, Arianminpathy Nimalan, Marcel Behr, Madeleine Durand, Mira Johri, Zamin Iqbal, Andry Rivo Rakotoarivelo, Rindra Vatosoa Randremanana, Niaina Rakotosamimanana, Simon Grandjean Lapierre

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting.

Methods: A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention.

Discussion: This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities.

Trial registration: ClinicalTrials.gov NCT05406453. Retrospectively registered on June 6, 2022.

Original language	English
Article number	717
Journal	Trials
Volume	25
Issue number	1
Early online date	25 Oct 2024
DOIs	https://doi.org/10.1186/s13063-024-08537-4
Publication status	E-pub ahead of print - 25 Oct 2024

Data Availability Statement

The final trial data will be available upon publication of the study result. Additional data will be available upon request to the corresponding author. Researchers are not limited to any contractual agreements that limit data accessibility.

Acknowledgements

We acknowledge partnering communities and local health institutions and representatives who have been supportive of this initiative since its inception.

Keywords

Cluster randomized controlled trial
Disease outbreak
Molecular epidemiology
Tuberculosis
Whole genome sequencing

ASJC Scopus subject areas

Medicine (miscellaneous)
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ametepe, E. S. A., Andriamanoha, N., Andrianomanana, F. R., Point, F., Mangahasimbola, R. T., Dyachenko, A., Hall, M., Gamana, T. M., Knoblauch, A. M., Razafindrasoa, Y. Y., Nimalan, A., Behr, M., Durand, M., Johri, M., Iqbal, Z., Rakotoarivelo, A. R., Randremanana, R. V., Rakotosamimanana, N., & Lapierre, S. G. (2024). Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar. Trials, 25(1), Article 717. Advance online publication. https://doi.org/10.1186/s13063-024-08537-4

Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar. / Ametepe, Emmanuelle Sandra Adjoa; Andriamanoha, Noela; Andrianomanana, Fanantenana Randria et al.
In: Trials, Vol. 25, No. 1, 717, 31.12.2024.

Research output: Contribution to journal › Article › peer-review

Ametepe, ESA, Andriamanoha, N, Andrianomanana, FR, Point, F, Mangahasimbola, RT, Dyachenko, A, Hall, M, Gamana, TM, Knoblauch, AM, Razafindrasoa, YY, Nimalan, A, Behr, M, Durand, M, Johri, M, Iqbal, Z, Rakotoarivelo, AR, Randremanana, RV, Rakotosamimanana, N & Lapierre, SG 2024, 'Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar', Trials, vol. 25, no. 1, 717. https://doi.org/10.1186/s13063-024-08537-4

Ametepe ESA, Andriamanoha N, Andrianomanana FR, Point F, Mangahasimbola RT, Dyachenko A et al. Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar. Trials. 2024 Dec 31;25(1):717. Epub 2024 Oct 25. doi: 10.1186/s13063-024-08537-4

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abstract = "Background: Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting. Methods: A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention. Discussion: This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities. Trial registration: ClinicalTrials.gov NCT05406453. Retrospectively registered on June 6, 2022.",

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AU - Ametepe, Emmanuelle Sandra Adjoa

AU - Andriamanoha, Noela

AU - Andrianomanana, Fanantenana Randria

AU - Point, Floriane

AU - Mangahasimbola, Reziky Tiandraza

AU - Dyachenko, Alina

AU - Hall, Michael

AU - Gamana, Theodora Mayouya

AU - Knoblauch, Astrid M.

AU - Razafindrasoa, Yemimah Yededyah

AU - Nimalan, Arianminpathy

AU - Behr, Marcel

AU - Durand, Madeleine

AU - Johri, Mira

AU - Iqbal, Zamin

AU - Rakotoarivelo, Andry Rivo

AU - Randremanana, Rindra Vatosoa

AU - Rakotosamimanana, Niaina

AU - Lapierre, Simon Grandjean

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N2 - Background: Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting. Methods: A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention. Discussion: This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities. Trial registration: ClinicalTrials.gov NCT05406453. Retrospectively registered on June 6, 2022.

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Whole genome sequencing of M. tuberculosis for disease control in high-burden settings: study protocol for a cluster randomized controlled trial evaluating different community-wide intervention strategies in rural Madagascar

Abstract

Data Availability Statement

Acknowledgements

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

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Cite this