Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis

Melanie H. Chitwood; Elizabeth L. Corbett; Victor Ndhlovu; Benjamin Sobkowiak; Caroline Colijn; Jason R. Andrews; Rachael M. Burke; Patrick G.T. Cudahy; Peter J. Dodd; Jeffrey W. Imai-Eaton; David M. Engelthaler; Megan Folkerts; Helena R.A. Feasey; Yu Lan; Jen Lewis; Jennifer McNichol; Nicolas A. Menzies; Geoffrey Chipungu; Marriott Nliwasa; Daniel M. Weinberger; Joshua L. Warren; Joshua A. Salomon; Peter MacPherson; Ted Cohen

doi:10.1371/journal.pgph.0004040

Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis

Melanie H. Chitwood^*, Elizabeth L. Corbett, Victor Ndhlovu, Benjamin Sobkowiak, Caroline Colijn, Jason R. Andrews, Rachael M. Burke, Patrick G.T. Cudahy, Peter J. Dodd, Jeffrey W. Imai-Eaton, David M. Engelthaler, Megan Folkerts, Helena R.A. Feasey, Yu Lan, Jen Lewis, Jennifer McNichol, Nicolas A. Menzies, Geoffrey Chipungu, Marriott Nliwasa, Daniel M. WeinbergerJoshua L. Warren, Joshua A. Salomon, Peter MacPherson, Ted Cohen^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e0004040
Pages (from-to)	1-18
Number of pages	18
Journal	PLOS Global Public Health
Volume	5
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgph.0004040
Publication status	Published - 2 Apr 2025

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Copyright: © 2025 Chitwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Mycobacterium tuberculosis population survey - Blantyre, Malawi
Feasey, H. (Creator), National Center for Biotechnology Information, 8 Feb 2025
https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1221228
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Chitwood, M. H., Corbett, E. L., Ndhlovu, V., Sobkowiak, B., Colijn, C., Andrews, J. R., Burke, R. M., Cudahy, P. G. T., Dodd, P. J., Imai-Eaton, J. W., Engelthaler, D. M., Folkerts, M., Feasey, H. R. A., Lan, Y., Lewis, J., McNichol, J., Menzies, N. A., Chipungu, G., Nliwasa, M., ... Cohen, T. (2025). Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis. PLOS Global Public Health, 5(4), 1-18. Article e0004040. https://doi.org/10.1371/journal.pgph.0004040

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title = "Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis",

abstract = "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.",

author = "Chitwood, {Melanie H.} and Corbett, {Elizabeth L.} and Victor Ndhlovu and Benjamin Sobkowiak and Caroline Colijn and Andrews, {Jason R.} and Burke, {Rachael M.} and Cudahy, {Patrick G.T.} and Dodd, {Peter J.} and Imai-Eaton, {Jeffrey W.} and Engelthaler, {David M.} and Megan Folkerts and Feasey, {Helena R.A.} and Yu Lan and Jen Lewis and Jennifer McNichol and Menzies, {Nicolas A.} and Geoffrey Chipungu and Marriott Nliwasa and Weinberger, {Daniel M.} and Warren, {Joshua L.} and Salomon, {Joshua A.} and Peter MacPherson and Ted Cohen",

note = "Funding: Funding: MHC, ELC, VN, SB, CC, JRA, PGTC, PJD, DME, MF, YL, JL, NAM, JLW, JAS, TC acknowledge funding from the National Institute of Allergy and Infectious Diseases (NIAID) (R01AI147854) (https://www.niaid.nih.gov/). JWI-E acknowledges funding from the Bill & Melinda Gates Foundation (INV-006733, INV-002606) (https://www.gatesfoundation.org/) and the MRC Centre for Global Infectious Disease Analysis (reference MR/X020258/1), funded by the UK Medical Research Council (MRC)(https://www.ukri.org/councils/mrc/). This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking.",

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language = "English",

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Chitwood, MH, Corbett, EL, Ndhlovu, V, Sobkowiak, B, Colijn, C, Andrews, JR, Burke, RM, Cudahy, PGT, Dodd, PJ, Imai-Eaton, JW, Engelthaler, DM, Folkerts, M, Feasey, HRA, Lan, Y, Lewis, J, McNichol, J, Menzies, NA, Chipungu, G, Nliwasa, M, Weinberger, DM, Warren, JL, Salomon, JA, MacPherson, P & Cohen, T 2025, 'Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis', PLOS Global Public Health, vol. 5, no. 4, e0004040, pp. 1-18. https://doi.org/10.1371/journal.pgph.0004040

TY - JOUR

T1 - Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi

T2 - a genomic and spatial analysis

AU - Chitwood, Melanie H.

AU - Corbett, Elizabeth L.

AU - Ndhlovu, Victor

AU - Sobkowiak, Benjamin

AU - Colijn, Caroline

AU - Andrews, Jason R.

AU - Burke, Rachael M.

AU - Cudahy, Patrick G.T.

AU - Dodd, Peter J.

AU - Imai-Eaton, Jeffrey W.

AU - Engelthaler, David M.

AU - Folkerts, Megan

AU - Feasey, Helena R.A.

AU - Lan, Yu

AU - Lewis, Jen

AU - McNichol, Jennifer

AU - Menzies, Nicolas A.

AU - Chipungu, Geoffrey

AU - Nliwasa, Marriott

AU - Weinberger, Daniel M.

AU - Warren, Joshua L.

AU - Salomon, Joshua A.

AU - MacPherson, Peter

AU - Cohen, Ted

N1 - Funding: Funding: MHC, ELC, VN, SB, CC, JRA, PGTC, PJD, DME, MF, YL, JL, NAM, JLW, JAS, TC acknowledge funding from the National Institute of Allergy and Infectious Diseases (NIAID) (R01AI147854) (https://www.niaid.nih.gov/). JWI-E acknowledges funding from the Bill & Melinda Gates Foundation (INV-006733, INV-002606) (https://www.gatesfoundation.org/) and the MRC Centre for Global Infectious Disease Analysis (reference MR/X020258/1), funded by the UK Medical Research Council (MRC)(https://www.ukri.org/councils/mrc/). This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking.

PY - 2025/4/2

Y1 - 2025/4/2

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgph.0004040

DO - 10.1371/journal.pgph.0004040

M3 - Article

SN - 2767-3375

VL - 5

SP - 1

EP - 18

JO - PLOS Global Public Health

JF - PLOS Global Public Health

IS - 4

M1 - e0004040

ER -

Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis

Abstract

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Mycobacterium tuberculosis population survey - Blantyre, Malawi

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