Using parasite genetic and human mobility data to infer local and cross-border malaria connectivity in Southern Africa

  1. Sofonias K Tessema  Is a corresponding author
  2. Amy Wesolowski
  3. Anna Chen
  4. Maxwell Murphy
  5. Jordan Wilheim
  6. Anna-Rosa Mupiri
  7. Nick W Ruktanonchai
  8. Victor A Alegana
  9. Andrew J Tatem
  10. Munyaradzi Tambo
  11. Bradley Didier
  12. Justin M Cohen
  13. Adam Bennett
  14. Hugh JW Sturrock
  15. Roland Gosling
  16. Michelle S Hsiang
  17. David L Smith
  18. Davis R Mumbengegwi
  19. Jennifer L Smith
  20. Bryan Greenhouse
  1. University of California, San Francisco, United States
  2. Johns Hopkins Bloomberg School of Public Health, United States
  3. University of Namibia, Namibia
  4. University of Southampton, United Kingdom
  5. Clinton Health Access Initiative, United States
  6. University of Washington, United States
  7. University of Texas Southwestern Medical Center, United States

Abstract

Local and cross-border importation remain major challenges to malaria elimination and are difficult to measure using traditional surveillance data. To address this challenge, we systematically collected parasite genetic data and travel history from thousands of malaria cases across northeastern Namibia and estimated human mobility from mobile phone data. We observed strong fine-scale spatial structure in local parasite populations, providing positive evidence that the majority of cases were due to local transmission. This result was largely consistent with estimates from mobile phone and travel history data. However, genetic data identified more detailed and extensive evidence of parasite connectivity over hundreds of kilometers than the other data, within Namibia and across the Angolan and Zambian borders. Our results provide a framework for incorporating genetic data into malaria surveillance and provide evidence that both strengthening of local interventions and regional coordination are likely necessary to eliminate malaria in this region of Southern Africa.

Data availability

All data generated or analyzed during this study are included in the manuscript and supplementary files.

Article and author information

Author details

  1. Sofonias K Tessema

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    For correspondence
    SofoniasK.Tessema@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1057-5310
  2. Amy Wesolowski

    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6320-3575
  3. Anna Chen

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Maxwell Murphy

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0332-4388
  5. Jordan Wilheim

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Anna-Rosa Mupiri

    Multidisciplinary Research Center, University of Namibia, Windhoek, Namibia
    Competing interests
    The authors declare that no competing interests exist.
  7. Nick W Ruktanonchai

    Geography and Environment, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Victor A Alegana

    Geography and Environment, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Andrew J Tatem

    Geography and Environment, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Munyaradzi Tambo

    Multidisciplinary Research Center, University of Namibia, Windhoek, Namibia
    Competing interests
    The authors declare that no competing interests exist.
  11. Bradley Didier

    Clinton Health Access Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Justin M Cohen

    Clinton Health Access Initiative, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Adam Bennett

    Institute of Global Health Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Hugh JW Sturrock

    Institute of Global Health Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Roland Gosling

    Global Health Group, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Michelle S Hsiang

    Institute of Global Health Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. David L Smith

    Institute of Health Metrics and Evaluation, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4367-3849
  18. Davis R Mumbengegwi

    Multidisciplinary Research Center, University of Namibia, Windhoek, Namibia
    Competing interests
    The authors declare that no competing interests exist.
  19. Jennifer L Smith

    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Bryan Greenhouse

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

Bill and Melinda Gates Foundation

  • Sofonias K Tessema
  • Bryan Greenhouse

Burroughs Wellcome Fund

  • Amy Wesolowski

National Institutes of Health

  • Amy Wesolowski

Chan Zuckerberg Biohub

  • Bryan Greenhouse

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ben Cooper, Mahidol Oxford Tropical Medicine Research Unit, Thailand

Ethics

Human subjects: Ethical approval for the study was obtained from the Institutional Review Boards of the University of Namibia and the University of California, San Francisco (Identification numbers 15-17422 and 14-14576). Informed consent was obtained from all participants or the parents of all children participated in the Zambezi study. For the Kavango study, IRB approval was obtained but no informed consent was collected as all samples (used RDTs) and de-identified data were collected during routine surveillance.

Version history

  1. Received: November 9, 2018
  2. Accepted: March 6, 2019
  3. Accepted Manuscript published: April 2, 2019 (version 1)
  4. Version of Record published: April 23, 2019 (version 2)

Copyright

© 2019, Tessema et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sofonias K Tessema
  2. Amy Wesolowski
  3. Anna Chen
  4. Maxwell Murphy
  5. Jordan Wilheim
  6. Anna-Rosa Mupiri
  7. Nick W Ruktanonchai
  8. Victor A Alegana
  9. Andrew J Tatem
  10. Munyaradzi Tambo
  11. Bradley Didier
  12. Justin M Cohen
  13. Adam Bennett
  14. Hugh JW Sturrock
  15. Roland Gosling
  16. Michelle S Hsiang
  17. David L Smith
  18. Davis R Mumbengegwi
  19. Jennifer L Smith
  20. Bryan Greenhouse
(2019)
Using parasite genetic and human mobility data to infer local and cross-border malaria connectivity in Southern Africa
eLife 8:e43510.
https://doi.org/10.7554/eLife.43510

Share this article

https://doi.org/10.7554/eLife.43510

Further reading

  1. Genetic analyses help to pinpoint where people got infected with malaria, enabling better interventions on the ground.

    1. Epidemiology and Global Health
    Sean V Connelly, Nicholas F Brazeau ... Jeffrey A Bailey
    Research Article

    Background:

    The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.

    Methods:

    To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.

    Results:

    Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.

    Conclusions:

    Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.

    Funding:

    This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.