Changing patterns of human migrations shaped the global population structure of Mycobacterium tuberculosis in France

Maxime Barbier,Anne-Sophie Ronnaux-Baron,Michèle Pérouse De Montclos,Philip Supply,Isabelle Fredenucci,Véronique Jacomo,Thierry Wirth,Sandrine Boisset,Florence Ader,Gérard Carret,Jean-Philippe Rasigade,Charlotte Genestet,Gérard Lina,Christine Godin-Benhaim,Oana Dumitrescu,Catherine Pichat,Jean-Pierre Flandrois,Anne Carricajo,Ghislaine Blasquez

doi:10.1038/s41598-018-24034-6

Abstract

Mycobacterium tuberculosis (Mtb) exhibits a structured phylogeographic distribution worldwide linked with human migrations. We sought to infer how the interactions between distinct human populations shape the global population structure of Mtb on a regional scale. We applied the recently described timescaled haplotypic density (THD) technique on 638 minisatellite-based Mtb genotypes from French tuberculosis patients. THD with a long-term (200 y) timescale indicated that Mtb population in France had been mostly influenced by interactions with Eastern and Southern Europe and, to a lesser extent, Northern and Middle Africa, consistent with historical migrations favored by geographic proximity or commercial exchanges with former French colonies. Restricting the timescale to 20 y, THD identified a sustained influence of Northern Africa, but not Europe where tuberculosis incidence decreased sharply. Evolving interactions between human populations, thus, measurably influence the local population structure of Mtb. Relevant information on such interactions can be inferred using THD from Mtb genotypes.

Highlights

Tuberculosis, one of the oldest diseases known to humanity, is an ongoing public health threat in many low-income countries and a re-emerging disease in several higher-income countries[1,2,3]
We investigated a cohort of 638 tuberculosis patients whose infecting strains were genotyped using spoligotyping[16] and variable number of tandem repeats (VNTR)[17] methods
Patients were retrieved from the database of the Observatoire Rhône-Alpin des Mycobactéries (ORAM), a regional network of healthcare institutions involved in the monitoring of tuberculosis in the French Rhône-Alpes region, an area with ~6.5 million inhabitants and a population density of 150 inhabitants per km[2]

Summary

Introduction

Tuberculosis, one of the oldest diseases known to humanity, is an ongoing public health threat in many low-income countries and a re-emerging disease in several higher-income countries[1,2,3]. Fine-grained phylogeographic studies without the cost and time constraints of international sampling, one might consider Mtb strains infecting foreign-born patients as proxies of the circulating strains in the patients country of origin[11,15] Under this assumption, a representative sample of Mtb isolates from an area of interest should enable to infer past transmission events involving the countries of origin of non-native patients. A representative sample of Mtb isolates from an area of interest should enable to infer past transmission events involving the countries of origin of non-native patients Based on this rationale, we performed a comprehensive phylogeographic analysis of global Mtb strains circulating in the Rhônes-Alpes region of France, a low-incidence country where two thirds of cases involve foreign-born patients[13]. To detect temporal changes in transmission patterns, we built upon a recently published phylogenetic analysis method, namely timescaled haplotypic density (THD)[18], to estimate the intensity of Mtb exchanges between native and foreign populations over short- and long-term time scales and we interpreted the inferred results in relation with known historical and sociological events

Methods

Results

Conclusion