Genomic, spatial, and epidemiological analysis to inform targeted TB interventions in Moldova

Genomic, Spatial and Epidemiological Analysis to Inform Targeted TB Interventions in Moldova

Project PeriodFebruary 2018 to December 2020
Principal InvestigatorTed Cohen
Subcontract InstitutionsCenter for Health Policies and Studies (Center PAS), Moldova;  Harvard T.H. Chan School of Public Health; Institute of Phthisiopneumology; Simon Fraser University and TGen
Location of InterestMoldova
FundingVital Strategies, Inc. via USAID

Public Heatlh Relevance: Global progress toward the control of tuberculosis (TB) is not on pace to meet post-2015 TB elimination strategy goals of 80% reduction in TB deaths, 60% reduction in TB incidence, and zero catastrophic costs for families affected by TB by 2030. Transmission dynamic modeling studies have concluded that these targets are unlikely to be reached in countries where the majority of global TB cases occur (i.e. India and China), even assuming substantial improvement in and scale up of existing approaches for TB control, including active case finding, access to new diagnostics and better treatment, and widespread use of preventive therapy.1  This effort will constitute the first attempt to use WGS to fully understand TB transmission at the level of an entire high incidence country and to inform targeted interventions.

[1] Houben R et al. Feasibility of achieving the post-2015 Global TB Targets in South Africa, China and India: A combined analysis of 11 models. Lancet Global Health 2016.

Project Summary: The Republic of Moldova is a small country in Eastern Europe struggling to interrupt ongoing transmission of multidrug-resistant TB (MDR-TB). This three-year prospective observational study brings together pathogen genomic, spatial, epidemiological, demographic, and laboratory information in an effort to better understand this epidemic.

This study aims to 1) fully characterize tuberculosis (TB) transmission patterns within the Republic of Moldova; 2) better understand the relative contribution of acquired and transmitted resistance to the MDR- TB epidemic in Moldova; 3) Understand how whole genome sequencing (WGS) can be used to inform the rational targeting of TB interventions; 4) build local capacity for interpreting WGS data and understanding its utility to inform local responses; and 5) estimate costs and explore the feasibility of routine use of WGS within the Moldovan TB.

This work is being carried out in Moldova through identifying all TB patients with a positive culture over the course of 24 months (January 2018 to December 2019). This work will build off of the strong existing infrastructure to extract TB DNA from the initial cultures of all culture-positive TB suspects and perform WGS on these samples. It was estimated that this prospective collection of strains would result in WGS of approximately 1,800 samples; however, final enrollment numbers reached  > 2,500.