Whole Genome Sequencing of Tuberculosis for Disease Control in Madagascar

Study Overview
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Brief Summary
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Tuberculosis (TB) whole genome sequencing (WGS) allows outbreak identification and disease transmission tracking. It is hypothesized that prospective WGS-guided epidemiological investigations improve case detection compared to current best practices by adapting contact tracing strategies to local transmission patterns. A cluster randomized controlled trial (cRCT) will be performed in high TB incidence villages of Haute Matsiatra region in Madagascar. Communities will be randomized in three separate TB control strategies comparing (1) standard of care, (2) the World Health Organization (WHO) recommended best practices and (3) a novel intervention involving TB WGS cluster-guided epidemiological investigations. The incremental value of TB WGS on case notifications and reduction of TB burden will be measured. Secondary studies will be nested within this cRCT will include: A qualitative study which will increase the understanding of the factors facilitating and hindering implementation of WGS-based diagnostics within health systems. A cost effectiveness analysis study which will measure the cost effectiveness of newly implemented laboratory methods. Field and genomic epidemiology data from this project will inform future work on the design of community-level TB elimination strategies in collaboration with Madagascar National TB program

Official Title
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Whole Genome Sequencing of Tuberculosis for Disease Control in Madagascar - A Cluster Randomized Controlled Trial to Evaluate Different Community-wide Intervention Strategies.

Conditions
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Tuberculosis

Intervention / Treatment
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* Other: Whole Genome Sequencing testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects suspected TB subject living in the study area Exclusion Criteria: unable to take a sputum sample
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: cRCT
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Madagascar standard of care<br>Description : Passive case finding, Smear microscopy testing, and household contact tracing | |
| No Intervention: Best practices<br>Description : Active case finding, Smear microscopy Xpert MTB/RIF Ultra testing (= rapid test by Genexpert for tuberculosis (TB) and rifampin resistance (RIF-R)) and household contact tracing | |
| Experimental: Novel intervention<br>Description : Active case finding, Smear microscopy Xpert MTB/RIF Ultra testing and household contact tracing | Other: Whole Genome Sequencing testing<br>* Whole Genome Sequencing testing, community-based contact tracing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the total number of TB cases detected / 100 000 inhabitants | total number of TB cases detected / 100,000 inhabitants / year in each group during the first year of the intervention. | an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whole genome sequencing, cluster randomized controlled trial