Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania
Authors: Zwyer Michaela , Rutaihwa Liliana K. , Windels Etthel , Hella Jerry , Menardo Fabrizio , Sasamalo Mohamed , 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 , Anchalee Avihingsanon , Xu Zhi Ming , Fellay Jacques , Portevin Damien , Reither Klaus , Stadler Tanja , Gagneux Sebastien , Brites Daniela 
Published: September 2022

In settings with high tuberculosis (TB) endemicity, various 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 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 our 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.

Author summary

Tuberculosis (TB) is the deadliest human infectious disease caused by one single agent, Mycobacterium tuberculosis (Mtb). The origins of Mtb have been traced to East Africa millennia ago, where it likely became adapted to infect and transmit in humans. Here we show that in Dar es Salaam, Tanzania, an East African setting with a very high burden of TB, infections are caused by distinct Mtb genotypes introduced in recent evolutionary times from different parts of the world. These genotypes differed in traits important to Mtb transmission in the Dar es Salaam host population; while some Mtb genotypes transmitted more efficiently during a certain period of time, others elicited that patients would be infectious for longer periods. These traits evolved independently in the different Mtb genotypes and could not be explained by the time of co-existence between the host population and the pathogen. This suggests that bacterial factors are important determinants of the TB epidemic. More generally, we demonstrate that distinct pathogenic life history characteristics can co-exist in one host population.