Tuberculosis (TB) still represents a significant global health problem, with an estimated 11 million new cases and almost 2 million deaths due to this disease annually. Morocco and Pakistan are among 30 high TB burden countries which account for nearly 90% of all estimated incident cases worldwide. Recently, Europe has witnessed increased migratory flows from Morocco and Pakistan, due to economic and military crisis in the Middle East and Africa. The spread of TB, including drug-resistant TB, from these regions, may have a detrimental impact on the epidemiology of TB in Europe and globally. It is therefore a high priority to carefully monitor the transmission of TB in these countries. One of the key strategies for TB control relies on the identification of patients involved in the same chain of remote or recent transmission. This is achieved through a population-based genotyping surveillance. Two major genotyping assays, namely spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing have been used in TB epidemiological studies. With the advent of next-generation sequencing technology, whole-genome sequencing (WGS) has been increasingly introduced into TB research. WGS offers an excellent resolution of M. tuberculosis (MTB) isolates, and thus delineates transmission routes with highest accuracy. Whole-genome single nucleotide polymorphism (wgSNP) analysis allows not only to accurately determine genetic relatedness between the isolates, but also to efficiently detect mutations associated with drug resistance. Furthermore, several pipelines have been developed to extract spoligotypes and MIRU-VNTR profiles from WGS data, an approach referred to as in silico genotyping. The aim of this project is to use WGS to explore the genetic structure of MTB isolates from Morocco and Pakistan to infer possible transmission events and to predict drug susceptibility profile of each isolate.
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