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Abstract

Genomic surveillance of pathogens important to public health, such as (Mtb), offers the opportunity to characterize the geographic movements of pathogens on a range of spatial and temporal scales and to explore the consequences of these inferred movements on the impacts of public health interventions. Pathogen movements can affect the impact of interventions that are geographically focused, with interventions in high-transmission areas, potentially leading to indirect benefits in other locations due to the prevention of transmission. We supplemented a large genomic surveillance dataset from Blantyre, Malawi (518 Lineage 4 sequences and 103 Lineage 1 sequences) with publicly available sequences collected across the world from 2015 to 2019 (910 Lineage 4 sequences and 445 Lineage 1 sequences) to reconstruct global and regional movements of Mtb in order to clarify the extent of importation into Blantyre. Standard phylogeographic methods are unsuitable for this task because they do not account for sampling heterogeneity across locations, so we build on a new method called sampling-aware ancestral state inference, incorporating wide disparities in the sampling fractions between different regions across the world, and also the fact that sampling only occurred from 2015 to 2019. Reconstructed phylogenetic trees contain strong signals of spatial localization of individual clades, with very limited numbers of introductions to, or exports from, Blantyre, and considerable movements within the city itself. Inferring which zone of the Blantyre nodes of the tree was in allows us to perform simple simulations of geographically focused interventions such as active case finding (ACF). We find that zone-focused ACF in Blantyre is likely to have modest impacts, with a focus on Zones 2 and 4 likely to have the most impact. As genomic surveillance becomes more commonplace, analyses such as this may be useful for public health practitioners developing interventions to reduce local TB transmission and incidence.

Funding
This study was supported by the:
  • Wellcome (Award 304666/Z/23/Z)
    • Principal Award Recipient: PeterMacPherson
  • NIHR Global Health Research Professorship (Award NIHR304311)
    • Principal Award Recipient: PeterMacPherson
  • Michael Smith Health Research BC (Award RT-2023-3052)
    • Principal Award Recipient: BradleyR Jones
  • National Sciences and Engineering Research Council of Canada (NSERC) Postgraduate Scholarship
    • Principal Award Recipient: JenniferMcNichol
  • Foreign, Commonwealth and Development Office (Award Leaving no-one behind: transforming gendered pathways to health for TB 2018/S 196-443482)
    • Principal Award Recipient: MphatsoD. Phiri
  • National Institutes of Health (Award US NIH R01 R01AI147854)
    • Principal Award Recipient: TedCohen
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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/content/journal/mgen/10.1099/mgen.0.001674
2026-04-08
2026-04-10

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References

  1. Beams AB, Song Y, McNichol J, Jones BR, Sobkowiak B et al.Genomic epidemiology of Mycobacterium tuberculosis in Malawi: using global phylogeography to understand the impact of geographically- focused interventions FigShare 2026 [View Article]
    [Google Scholar]
  2. Reid M, Agbassi YJP, Arinaminpathy N, Bercasio A, Bhargava A et al. Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis. Lancet 2023; 402:1473–1498 [View Article]
    [Google Scholar]
  3. Goletti D, Meintjes G, Andrade BB, Zumla A, Shan Lee S. Insights from the 2024 WHO Global Tuberculosis Report - more comprehensive action, innovation, and investments required for achieving WHO End TB goals. Int J Infect Dis 2025; 150:107325 [View Article] [PubMed]
    [Google Scholar]
  4. Feasey HRA, Khundi M, Nzawa Soko R, Nightingale E, Burke RM et al. Prevalence of bacteriologically-confirmed pulmonary tuberculosis in urban Blantyre, Malawi 2019–20: substantial decline compared to 2013–14 national survey. PLoS Glob Public Health 2023; 3:e0001911 [View Article] [PubMed]
    [Google Scholar]
  5. Dowdy DW, Golub JE, Chaisson RE, Saraceni V. Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics. Proc Natl Acad Sci USA 2012; 109:9557–9562 [View Article]
    [Google Scholar]
  6. Brown TS, Robinson DA, Buckee CO, Mathema B. Connecting the dots: understanding how human mobility shapes TB epidemics. Trends Microbiol 2022; 30:1036–1044 [View Article] [PubMed]
    [Google Scholar]
  7. Colijn C, Cohen T, Murray M. Emergent heterogeneity in declining tuberculosis epidemics. J Theor Biol 2007; 247:765–774 [View Article] [PubMed]
    [Google Scholar]
  8. Khundi M, Carpenter JR, Nliwasa M, Cohen T, Corbett EL et al. Effectiveness of spatially targeted interventions for control of HIV, tuberculosis, leprosy and malaria: a systematic review. BMJ Open 2021; 11:e044715 [View Article] [PubMed]
    [Google Scholar]
  9. MacPherson P, Shanaube K, Phiri MD, Rickman HM, Horton KC et al. Community-based active-case finding for tuberculosis: navigating a complex minefield. BMC Glob Public Health 2024; 2:9 [View Article] [PubMed]
    [Google Scholar]
  10. Ayabina DV, Gomes MGM, Nguyen NV, Vo L, Shreshta S et al. The impact of active case finding on transmission dynamics of tuberculosis: a modelling study. PLoS One 2021; 16:e0257242 [View Article] [PubMed]
    [Google Scholar]
  11. Burke RM, Nliwasa M, Feasey HRA, Chaisson LH, Golub JE et al. Community-based active case-finding interventions for tuberculosis: a systematic review. Lancet Public Health 2021; 6:e283–e299 [View Article] [PubMed]
    [Google Scholar]
  12. Feasey HRA, Khundi M, Soko RN, Bottomley C, Chiume L et al. Impact of active case-finding for tuberculosis on case-notifications in Blantyre, Malawi: a community-based cluster-randomised trial (SCALE). PLoS Glob Public Health 2023; 3:e0002683 [View Article] [PubMed]
    [Google Scholar]
  13. Telisinghe L, Ruperez M, Amofa-Sekyi M, Mwenge L, Mainga T et al. Does tuberculosis screening improve individual outcomes? A systematic review. EClinicalMedicine 2021; 40:101127 [View Article] [PubMed]
    [Google Scholar]
  14. Shah AP, Dave JD, Makwana MN, Rupani MP, Shah IA. A mixed-methods study on impact of active case finding on pulmonary tuberculosis treatment outcomes in India. Arch Public Health 2024; 82:92 [View Article] [PubMed]
    [Google Scholar]
  15. Dinh LV, Wiemers AMC, Forse RJ, Phan YTH, Codlin AJ et al. Comparing catastrophic costs: active vs. passive tuberculosis case finding in urban Vietnam. Trop Med Infect Dis 2023; 8:423 [View Article] [PubMed]
    [Google Scholar]
  16. O’Cathail C, Ahamed A, Burgin J, Cummins C, Devaraj R et al. The European nucleotide archive in 2024. Nucleic Acids Res 2025; 53:D49–D55 [View Article] [PubMed]
    [Google Scholar]
  17. Huang C-C, Trevisi L, Becerra MC, Calderón RI, Contreras CC et al. Spatial scale of tuberculosis transmission in Lima, Peru. Proc Natl Acad Sci USA 2022; 119:e2207022119 [View Article]
    [Google Scholar]
  18. Cudahy PGT, Andrews JR, Bilinski A, Dowdy DW, Mathema B et al. Spatially targeted screening to reduce tuberculosis transmission in high-incidence settings. Lancet Infect Dis 2019; 19:e89–e95 [View Article] [PubMed]
    [Google Scholar]
  19. Morey-León G, Mejía-Ponce PM, Fernández-Cadena JC, García-Moreira E, Andrade-Molina D et al. Global epidemiology of Mycobacterium tuberculosis lineage 4 insights from Ecuadorian genomic data. Sci Rep 2025; 15:3823 [View Article] [PubMed]
    [Google Scholar]
  20. Glynn JR, Alghamdi S, Mallard K, McNerney R, Ndlovu R et al. Changes in Mycobacterium tuberculosis genotype families over 20 years in a population-based study in Northern Malawi. PLoS One 2010; 5:e12259 [View Article] [PubMed]
    [Google Scholar]
  21. Sobkowiak B, Banda L, Mzembe T, Crampin AC, Glynn JR et al. Bayesian reconstruction of Mycobacterium tuberculosis transmission networks in a high incidence area over two decades in Malawi reveals associated risk factors and genomic variants. Microb Genom 2020; 6:e000361 [View Article] [PubMed]
    [Google Scholar]
  22. Chitwood MH, Corbett EL, Ndhlovu V, Sobkowiak B, Colijn C et al. Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis. PLoS Glob Public Health 2025; 5:e0004040 [View Article] [PubMed]
    [Google Scholar]
  23. Liu P, Song Y, Colijn C, MacPherson A. The impact of sampling bias on viral phylogeographic reconstruction. PLoS Glob Public Health 2022; 2:e0000577 [View Article] [PubMed]
    [Google Scholar]
  24. Song Y, Gill I, MacPherson A, Colijn C. Sampling-aware ancestral state inference. Evol Biol2025 2025 [View Article]
    [Google Scholar]
  25. Department of Tourism Malawi domestic and outbound tourism survey report. Malawi National Office of Statistics; 2019
  26. Dhakal A. Food insecurity and irregular labour migration from northern Malawi to South Africa; 2024
  27. Nshimbi CC. The human side of regions: informal cross-border traders in the Zambia–Malawi–Mozambique growth triangle and prospects for integrating Southern Africa. J Borderl Stud 2020; 35:75–97 [View Article]
    [Google Scholar]
  28. Malavoloneque M, Huria A. Making trade safer for women cross-border traders in Mozambique and Malawi; 2023Mar8 https://blogs.worldbank.org/en/trade/making-trade-safer-women-cross-border-traders-mozambique-and-malawi accessed 20 January 2026
  29. World Health Organization Global programme on tuberculosis & lung health. World Health Organization; 2024
  30. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv1303.3997 2013
    [Google Scholar]
  31. Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V et al. Twelve years of SAMtools and BCFtools. Gigascience 2021; 10:giab008 [View Article]
    [Google Scholar]
  32. Sobkowiak B, Cudahy P, Chitwood MH, Clark TG, Colijn C et al. A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission. Genome Med 2025; 17:8 [View Article] [PubMed]
    [Google Scholar]
  33. Poplin R, Ruano-Rubio V, DePristo MA, Fennell TJ, Carneiro MO et al. Scaling accurate genetic variant discovery to tens of thousands of samples. Genomics201178 2017 [View Article]
    [Google Scholar]
  34. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 2020; 37:1530–1534 [View Article]
    [Google Scholar]
  35. Didelot X, Croucher NJ, Bentley SD, Harris SR, Wilson DJ. Bayesian inference of ancestral dates on bacterial phylogenetic trees. Nucleic Acids Res 2018; 46:e134 [View Article] [PubMed]
    [Google Scholar]
  36. Jaemsai B, Palittapongarnpim P, Aiewsakun P. South Asian origin and global transmission history of Mycobacterium tuberculosis lineage 4. mSystems 2025; 10:e0042725 [View Article] [PubMed]
    [Google Scholar]
  37. Menardo F, Duchêne S, Brites D, Gagneux S. The molecular clock of Mycobacterium tuberculosis. PLoS Pathog 2019; 15:e1008067 [View Article] [PubMed]
    [Google Scholar]
  38. FitzJohn RG. Diversitree: comparative phylogenetic analyses of diversification in R. Methods Ecol Evol 2012; 3:1084–1092 [View Article]
    [Google Scholar]
  39. Maddison WP, Midford PE, Otto SP. Estimating a binary character’s effect on speciation and extinction. Syst Biol 2007; 56:701–710 [View Article] [PubMed]
    [Google Scholar]
  40. FitzJohn RG, Maddison WP, Otto SP. Estimating trait-dependent speciation and extinction rates from incompletely resolved phylogenies. Syst Biol 2009; 58:595–611 [View Article] [PubMed]
    [Google Scholar]
  41. Stadler T, Kouyos R, von Wyl V, Yerly S, Böni J et al. Estimating the basic reproductive number from viral sequence data. Mol Biol Evol 2012; 29:347–357 [View Article] [PubMed]
    [Google Scholar]
  42. Paradis E, Schliep K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 2019; 35:526–528 [View Article] [PubMed]
    [Google Scholar]
  43. Revell LJ. phytools 2.0: an updated R ecosystem for phylogenetic comparative methods (and other things). PeerJ 2024; 12:e16505 [View Article] [PubMed]
    [Google Scholar]
  44. Burke RM, Nliwasa M, Dodd PJ, Feasey HRA, Khundi M et al. Impact of community-wide tuberculosis active case finding and human immunodeficiency virus testing on tuberculosis trends in Malawi. Clin Infect Dis 2023; 77:94–100 [View Article]
    [Google Scholar]
  45. Feasey HRA, Burke RM, Nliwasa M, Chaisson LH, Golub JE et al. Do community-based active case-finding interventions have indirect impacts on wider TB case detection and determinants of subsequent TB testing behaviour? A systematic review. PLoS Glob Public Health 2021; 1:e0000088 [View Article] [PubMed]
    [Google Scholar]
  46. Chihota VN, Niehaus A, Streicher EM, Wang X, Sampson SL et al. Geospatial distribution of Mycobacterium tuberculosis genotypes in Africa. PLoS One 2018; 13:e0200632 [View Article]
    [Google Scholar]
  47. Dye C, Williams BG. Tuberculosis decline in populations affected by HIV: a retrospective study of 12 countries in the WHO African Region. Bull World Health Organ 2019; 97:405–414 [View Article] [PubMed]
    [Google Scholar]
  48. Dinkele R, Gessner S, McKerry A, Leonard B, Leukes J et al. Aerosolization of Mycobacterium tuberculosis by tidal breathing. Am J Respir Crit Care Med 2022; 206:206–216 [View Article] [PubMed]
    [Google Scholar]
  49. Turner RD, Chiu C, Churchyard GJ, Esmail H, Lewinsohn DM et al. Tuberculosis infectiousness and host susceptibility. J Infect Dis 2017; 216:S636–S643 [View Article] [PubMed]
    [Google Scholar]
  50. Gao J, May MR, Rannala B, Moore BR. Model misspecification misleads inference of the spatial dynamics of disease outbreaks. Proc Natl Acad Sci USA 2023; 120:e2213913120 [View Article]
    [Google Scholar]
  51. Lemey P, Rambaut A, Drummond AJ, Suchard MA. Bayesian phylogeography finds its roots. PLoS Comput Biol 2009; 5:e1000520 [View Article] [PubMed]
    [Google Scholar]
  52. Chen Z, Lemey P, Yu H. Approaches and challenges to inferring the geographical source of infectious disease outbreaks using genomic data. Lancet Microbe 2024; 5:e81–e92 [View Article]
    [Google Scholar]
  53. Glynn JR, Guerra-Assunção JA, Houben RMGJ, Sichali L, Mzembe T et al. Whole genome sequencing shows a low proportion of tuberculosis disease is attributable to known close contacts in rural Malawi. PLoS One 2015; 10:e0132840 [View Article] [PubMed]
    [Google Scholar]
  54. MacPherson EE, Phiri M, Sadalaki J, Nyongopa V, Desmond N et al. Sex, power, marginalisation and HIV amongst young fishermen in Malawi: exploring intersecting inequalities. Socl Sci Med 2020; 266:113429 [View Article]
    [Google Scholar]
  55. McLean E, Dube A, Kalobekamo F, Slaymaker E, Crampin AC et al. Local and long-distance migration among young people in rural Malawi: importance of age, sex and family. Wellcome Open Res 2024; 8:211 [View Article]
    [Google Scholar]
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