Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: A genomic and spatial analysis
Delays in identifying and treating individuals with infectious tuberculosis (TB) contribute to poor health outcomes and allow ongoing community transmission of M. tuberculosis (Mtb). Current recommendations for screening for tuberculosis specify community characteristics (e.g., areas with high local tuberculosis prevalence) that can be used to target screening within the general population. However, areas of higher tuberculosis burden are not necessarily areas with higher rates of transmission. We investigated the transmission of Mtb using high-resolution surveillance data in Blantyre, Malawi. We extracted and performed whole genome sequencing on mycobacterial DNA from cultured M. tuberculosis isolates obtained from culture-positive tuberculosis cases at the time of tuberculosis (TB) notification in Blantyre, Malawi between 2015-2019. We constructed putative transmission networks identified using TransPhylo and investigated individual and pair-wise demographic, clinical, and spatial factors associated with person-to-person transmission. We found that 56% of individuals with sequenced isolates had a probable transmission link to at least one other individual in the study. We identified thirteen putative transmission networks that included five or more individuals. Five of these networks had a single spatial focus of transmission in the city, and each focus centered in a distinct neighborhood in the city. We also found that approximately two-thirds of inferred transmission links occurred between individuals residing in different geographic zones of the city. While the majority of detected tuberculosis transmission events in Blantyre occurred between people living in different zones, there was evidence of distinct geographical concentration for five transmission networks. These findings suggest that targeted interventions in areas with evidence of localized transmission may be an effective local tactic, but will likely need to be augmented by city-wide interventions to improve case finding to have sustained impact.
Authors
- Yu Lan (ORCID: https://orcid.org/0000-0003-0373-1944)
- Geoffrey Chipungu (ORCID: https://orcid.org/0000-0002-3819-0300)
- Jen Lewis (ORCID: https://orcid.org/0000-0002-3765-1566)
- Benjamin Sobkowiak (ORCID: https://orcid.org/0000-0002-1382-1137)
- Joshua L. Warren (ORCID: https://orcid.org/0000-0002-6274-6970)
- Jeffrey W. Eaton (ORCID: https://orcid.org/0000-0001-7728-728X)
- Peter J. Dodd (ORCID: https://orcid.org/0000-0001-5825-9347)
- Peter MacPherson (ORCID: https://orcid.org/0000-0002-0329-9613)
- Megan Folkerts (ORCID: https://orcid.org/0000-0001-7430-1701)
- Melanie H. Chitwood (ORCID: https://orcid.org/0000-0002-9289-5694)
- Victor Ndhlovu (ORCID: https://orcid.org/0000-0003-1606-0959)
- Joshua A. Salomon (ORCID: https://orcid.org/0000-0003-3929-5515)
- Marriott Nliwasa (ORCID: https://orcid.org/0000-0002-3100-5512)
- Helena R. A. Feasey (ORCID: https://orcid.org/0000-0003-3109-6722)
- David M. Engelthaler (ORCID: https://orcid.org/0000-0001-5945-059X)
- Ted Cohen (ORCID: https://orcid.org/0000-0002-8091-7198)
- Nicolas A. Menzies (ORCID: https://orcid.org/0000-0002-2571-016X)
- Daniel M. Weinberger (ORCID: https://orcid.org/0000-0003-1178-8086)
- Patrick Cudahy (ORCID: https://orcid.org/0000-0003-4462-9567)
- Jason Randolph Andrews (ORCID: https://orcid.org/0000-0002-5967-251X)
- Rachael M. Burke (ORCID: https://orcid.org/0000-0002-2156-5030)
- Caroline Colijn (ORCID: https://orcid.org/0000-0001-6097-6708)
- Elizabeth Corbett (ORCID: https://orcid.org/0000-0003-4825-0415)
- Jennifer McNichol
Institutions
- Translational Genomics Research Institute (US)
- Center for Disease Dynamics, Economics & Policy (US)
- University of Liverpool (GB)
- University of St Andrews (GB)
- Simon Fraser University (CA)
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MW)
- Kamuzu Central Hospital (MW)
- Yale University (US)
- London School of Hygiene & Tropical Medicine (GB)
- Public Health Scotland (GB)
- Harvard Global Health Institute (US)
- Kamuzu University of Health Sciences (MW)
- Imperial College London (GB)
- University of Glasgow (GB)
- University of Sheffield (GB)
- Stanford University (US)
Publication Details
- Journal
- PLOS Global Public Health
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1371/journal.pgph.0004040
- Citations
- 2
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Bill and Melinda Gates Foundation
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Medical Research Council
- National Institute of Allergy and Infectious Diseases
- European and Developing Countries Clinical Trials Partnership