The Francis Crick Institute
journal.ppat.1010893 (1).pdf (1.71 MB)

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

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journal contribution
posted on 2023-04-20, 13:23 authored by Michaela Zwyer, Liliana K Rutaihwa, Etthel Windels, Jerry Hella, Fabrizio Menardo, Mohamed Sasamalo, Gregor Sommer, Lena Schmülling, Sonia Borrell, Miriam Reinhard, Anna Dötsch, Hellen Hiza, Christoph Stritt, George Sikalengo, Lukas Fenner, Bouke C De Jong, Midori Kato-Maeda, Levan Jugheli, Joel D Ernst, Stefan Niemann, Leila Jeljeli, Marie Ballif, Matthias Egger, Niaina Rakotosamimanana, Dorothy Yeboah-Manu, Prince Asare, Bijaya Malla, Horng Yunn Dou, Nicolas Zetola, Robert J Wilkinson, Helen Cox, E Jane Carter, Joachim Gnokoro, Marcel Yotebieng, Eduardo Gotuzzo, Alash'le Abimiku, Anchalee Avihingsanon, Zhi Ming Xu, Jacques Fellay, Damien Portevin, Klaus Reither, Tanja Stadler, Sebastien Gagneux, Daniela Brites
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.


Crick (Grant ID: CC2112, Grant title: Wilkinson CC2112)