Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania

Author:

Zwyer Michaela,Rutaihwa Liliana K.,Windels Etthel,Hella Jerry,Menardo Fabrizio,Sasamalo Mohamed,Sommer Gregor,Schmülling Lena,Borrell Sonia,Reinhard Miriam,Dötsch Anna,Hiza Hellen,Stritt Christoph,Sikalengo George,Fenner Lukas,De Jong Bouke C.,Kato-Maeda Midori,Jugheli Levan,Ernst Joel D.,Niemann Stefan,Jeljeli Leila,Ballif Marie,Egger Matthias,Rakotosamimanana Niaina,Yeboah-Manu Dorothy,Asare Prince,Malla Bijaya,Dou Horng Yunn,Zetola Nicolas,Wilkinson Robert J.,Cox Helen,Carter E Jane,Gnokoro Joachim,Yotebieng Marcel,Gotuzzo Eduardo,Abimiku Alash’le,Avihingsanon Anchalee,Xu Zhi Ming,Fellay Jacques,Portevin Damien,Reither Klaus,Stadler Tanja,Gagneux Sebastien,Brites DanielaORCID

Abstract

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

HORIZON EUROPE European Research Council

Welcome

Cancer Research UK

Medical Research Council

US National Institutes of Health

Swiss National Science Foundation

Publisher

Public Library of Science (PLoS)

Subject

Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology

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