Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania. Zwyer, M., Rutaihwa, L. K, Windels, E., Hella, J., Menardo, F., Sasamalo, M., Borrell, S., Reinhard, M., Dötsch, A., Hiza, H., Stritt, C., Sikalengo, G., Fenner, L., Jong, B. C D., Kato-Maeda, M., Jugheli, L., Ernst, J. D, Niemann, S., Jeljeli, L., Ballif, M., Egger, M., Rakotosamimanana, N., Yeboah-Manu, D., Asare, P., Malla, B., Dou, H. Y., Zetola, N., Wilkinson, R. J, Cox, H., Carter, E J., Gnokoro, J., Yotebieng, M., Gotuzzo, E., Abimiku, A., Anchalee, A., Xu, Z. M., Fellay, J., Portevin, D., Reither, K., Stadler, T., Gagneux, S., & Brites, D. medRxiv, Cold Spring Harbor Laboratory Press, sep, 2022.
Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania [link]Paper  doi  abstract   bibtex   
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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Swiss National Science Foundation (https://www.snf.ch; Grant No: CRSII5$\$_177163, 310030$\$_188888) and the European Research Council (https://erc.europa.eu/; Grant No: 883582). RJW is supported by the Francis Crick Institute which receives funding from Wellcome (FC0010218), Cancer Research UK (FC0010218), and the Medical Research Council (FC0010218). He also receives support from Welcome (203135). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Nordwest und Zentralschweiz gave ethical approval for this work Ethics committee of Ifakara Health Institute Institutional Review Board board gave ethical approval for this work. Ethics committee of the National Institute for Medical Research in Tanzania Medical Research Coordinating Committee gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors
@article{Zwyer2022,
abstract = {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. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This work was supported by the Swiss National Science Foundation (https://www.snf.ch; Grant No: CRSII5$\backslash${\_}177163, 310030$\backslash${\_}188888) and the European Research Council (https://erc.europa.eu/; Grant No: 883582). RJW is supported by the Francis Crick Institute which receives funding from Wellcome (FC0010218), Cancer Research UK (FC0010218), and the Medical Research Council (FC0010218). He also receives support from Welcome (203135). {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Nordwest und Zentralschweiz gave ethical approval for this work Ethics committee of Ifakara Health Institute Institutional Review Board board gave ethical approval for this work. Ethics committee of the National Institute for Medical Research in Tanzania Medical Research Coordinating Committee gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},
author = {Zwyer, Michalela and Rutaihwa, Liliana K and Windels, Etthel and Hella, Jerry and Menardo, Fabrizio and Sasamalo, Mohamed and Borrell, Sonia and Reinhard, Miriam and D{\"{o}}tsch, Anna and Hiza, Hellen and Stritt, Christoph and Sikalengo, George and Fenner, Lukas and Jong, Bouke C De and Kato-Maeda, Midori and Jugheli, Levan and Ernst, Joel D and Niemann, Stephan and Jeljeli, Leila and Ballif, Marie and Egger, Matthias and Rakotosamimanana, Niaina and Yeboah-Manu, Dorothy and Asare, Prince and Malla, Bijaya and Dou, Horng Yunn and Zetola, Nicolas and Wilkinson, Robert J and Cox, Helen and Carter, E Jane and Gnokoro, Joachim and Yotebieng, Marcel and Gotuzzo, Eduardo and Abimiku, Alash'le and Anchalee, Avihingsanon and Xu, Zhi Ming and Fellay, Jacques and Portevin, Damien and Reither, Klaus and Stadler, Tanja and Gagneux, Sebastien and Brites, Daniela},
doi = {10.1101/2022.09.29.22280296},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Zwyer et al. - 2022 - Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tan.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack},
mendeley-tags = {OA,fund{\_}ack},
month = {sep},
pages = {2022.09.29.22280296},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania}},
url = {https://www.medrxiv.org/content/10.1101/2022.09.29.22280296v1 https://www.medrxiv.org/content/10.1101/2022.09.29.22280296v1.abstract},
year = {2022}
}
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