Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns

doi:10.1038/s41467-019-10121-3

. 2019 Jun 17;10(1):2665.

doi: 10.1038/s41467-019-10121-3.

Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns

Amol C Shetty ^{1

2}, Christopher G Jacob ³, Fang Huang ⁴, Yao Li ⁵, Sonia Agrawal ^{6

7}, David L Saunders ⁸, Chanthap Lon ⁹, Mark M Fukuda ⁸, Pascal Ringwald ¹⁰, Elizabeth A Ashley ^{11

12}, Kay Thwe Han ¹³, Tin Maung Hlaing ¹⁴, Myaing M Nyunt ¹⁵, Joana C Silva ^{16

17}, Kathleen E Stewart ¹², Christopher V Plowe ¹⁵, Timothy D O'Connor ^{18

19}, Shannon Takala-Harrison ²⁰; Artemisinin Resistance Confirmation, Characterization, and Containment (ARC3) ; Artemisinin Resistance Containment and Elimination (ARCE) ; Tracking Resistance to Artemisinin Collaboration (TRAC)

Collaborators, Affiliations

Collaborators

Harald Noedl , Wasif A Khan , Paul Newton , Myat P Kyaw , Nicholas J White , Arjen M Dondorp , Nicholas P Day , Charles J Woodrow , Mehul Dhorda , M Abul Faiz , Rick M Fairhurst , Pharath Lim , Rupam Tripura , Mayfong Mayxay , Ye Htut , Francois Nosten , Aung Pyae Phyo , Sasithon Pukrittayakamee , Tran Tinh Hien , Nguyen Thanh Thuy Nhien , Olugbenga A Mokuolu , Caterina I Fanello , Marie A Onyamboko

Affiliations

¹ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. amolcarlshetty@gmail.com.
² Graduate Program in Epidemiology and Human Genetics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. amolcarlshetty@gmail.com.
³ Wellcome Sanger Institute, Hinxton, CB10 1SA, Cambridgeshire, UK.
⁴ National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Beijing, 102206, PR China.
⁵ Center for Geospatial Information Science, University of Maryland, College Park, MD, 20742, USA.
⁶ Graduate Program in Epidemiology and Human Genetics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
⁷ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
⁸ Armed Forces Research Institute of Medical Sciences, Bangkok, 10400, Thailand.
⁹ Armed Forces Research Institute of Medical Sciences, Khan Daun Penh, Phnom Penh, Cambodia.
¹⁰ Global Malaria Programme, World Health Organization, Geneva, 1202, Switzerland.
¹¹ Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
¹² Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
¹³ Department of Medical Research, Ministry of Health and Sports, Yangon, 11191, Myanmar.
¹⁴ Defence Services Medical Research Centre, Naypyitaw, Myanmar.
¹⁵ Duke Global Health Institute, Duke University, Durham, NC, 27710, USA.
¹⁶ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
¹⁷ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
¹⁸ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. timothydoconnor@gmail.com.
¹⁹ Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. timothydoconnor@gmail.com.
²⁰ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. stakala@som.umaryland.edu.

PMID: 31209259
PMCID: PMC6572796
DOI: 10.1038/s41467-019-10121-3

Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns

Amol C Shetty et al. Nat Commun. 2019.

. 2019 Jun 17;10(1):2665.

doi: 10.1038/s41467-019-10121-3.

Authors

Amol C Shetty ^{1

2}, Christopher G Jacob ³, Fang Huang ⁴, Yao Li ⁵, Sonia Agrawal ^{6

7}, David L Saunders ⁸, Chanthap Lon ⁹, Mark M Fukuda ⁸, Pascal Ringwald ¹⁰, Elizabeth A Ashley ^{11

12}, Kay Thwe Han ¹³, Tin Maung Hlaing ¹⁴, Myaing M Nyunt ¹⁵, Joana C Silva ^{16

17}, Kathleen E Stewart ¹², Christopher V Plowe ¹⁵, Timothy D O'Connor ^{18

19}, Shannon Takala-Harrison ²⁰; Artemisinin Resistance Confirmation, Characterization, and Containment (ARC3) ; Artemisinin Resistance Containment and Elimination (ARCE) ; Tracking Resistance to Artemisinin Collaboration (TRAC)

Collaborators

Harald Noedl , Wasif A Khan , Paul Newton , Myat P Kyaw , Nicholas J White , Arjen M Dondorp , Nicholas P Day , Charles J Woodrow , Mehul Dhorda , M Abul Faiz , Rick M Fairhurst , Pharath Lim , Rupam Tripura , Mayfong Mayxay , Ye Htut , Francois Nosten , Aung Pyae Phyo , Sasithon Pukrittayakamee , Tran Tinh Hien , Nguyen Thanh Thuy Nhien , Olugbenga A Mokuolu , Caterina I Fanello , Marie A Onyamboko

Affiliations

¹ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. amolcarlshetty@gmail.com.
² Graduate Program in Epidemiology and Human Genetics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. amolcarlshetty@gmail.com.
³ Wellcome Sanger Institute, Hinxton, CB10 1SA, Cambridgeshire, UK.
⁴ National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Beijing, 102206, PR China.
⁵ Center for Geospatial Information Science, University of Maryland, College Park, MD, 20742, USA.
⁶ Graduate Program in Epidemiology and Human Genetics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
⁷ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
⁸ Armed Forces Research Institute of Medical Sciences, Bangkok, 10400, Thailand.
⁹ Armed Forces Research Institute of Medical Sciences, Khan Daun Penh, Phnom Penh, Cambodia.
¹⁰ Global Malaria Programme, World Health Organization, Geneva, 1202, Switzerland.
¹¹ Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
¹² Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK.
¹³ Department of Medical Research, Ministry of Health and Sports, Yangon, 11191, Myanmar.
¹⁴ Defence Services Medical Research Centre, Naypyitaw, Myanmar.
¹⁵ Duke Global Health Institute, Duke University, Durham, NC, 27710, USA.
¹⁶ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
¹⁷ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
¹⁸ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. timothydoconnor@gmail.com.
¹⁹ Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. timothydoconnor@gmail.com.
²⁰ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. stakala@som.umaryland.edu.

PMID: 31209259
PMCID: PMC6572796
DOI: 10.1038/s41467-019-10121-3

Abstract

Estimates of Plasmodium falciparum migration may inform strategies for malaria elimination. Here we elucidate fine-scale parasite population structure and infer recent migration across Southeast Asia using identity-by-descent (IBD) approaches based on genome-wide single nucleotide polymorphisms called in 1722 samples from 54 districts. IBD estimates are consistent with isolation-by-distance. We observe greater sharing of larger IBD segments between artemisinin-resistant parasites versus sensitive parasites, which is consistent with the recent spread of drug resistance. Our IBD analyses reveal actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination, as well as asymmetrical migration identifying potential sources and sinks of migrating parasites.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1

Fig. 1

Sampling locations within the Greater Mekong Subregion and Bangladesh. Red circles mark districts where P. falciparum isolates were sampled. Circle area is proportional to the number of isolates sampled in that district. The SRTMGL3 elevation data was retrieved from the online EarthExplorer, courtesy of the NASA Land Processes Distributed Active Archive Center (LP DAAC), USGS/Earth Resources Observation and Science (EROS) Center, Sioux Falls, South Dakota, https://earthexplorer.usgs.gov/^–

Fig. 2

Fig. 2

Cumulative pairwise IBD sharing between all parasites. a All segments greater than 2 cM, b 2–15 cM, c 15–30 cM, and d greater than 30 cM. Panels b–d are subsets of panel a. Each tile denotes the cumulative IBD sharing between isolates. Bangladesh and Thailand are abbreviated as BD and TH, respectively. The color indicates the magnitude of total IBD sharing

Fig. 3

Fig. 3

Regional relatedness within and between districts. a All segments greater than 2 cM, b 2–15 cM, c 15–30 cM, and d greater than 30 cM. Sharing of larger IBD segments indicates more recent migration. Circles represent the average IBD sharing within a district while lines represent the average IBD sharing between two districts. The color indicates the magnitude of IBD sharing while the area of the circle represents the average number of segments shared. Only district-pairs with >3% isolate-pairs demonstrating IBD sharing are included. Map data: Google, 2018

Fig. 4

Fig. 4

Asymmetrical migration between districts in Cambodia. Directional migration was inferred using IBD estimates between nonadmixed and admixed isolates across districts. Statistically significant asymmetrical migration between two districts is indicated by an arrow. Malaria endemicity is indicated in green. Map data: Malaria Atlas Project (https://map.ox.ac.uk/)

Fig. 5

Fig. 5

EEMS contours illustrating relative migration. Each circle is a deme consisting of one or more districts, with area proportional to the number of isolates in the deme. Panels depict relative parasite migration in a Southeast Asia and b Cambodia, with brown contours indicating lower levels of migration and blue contours indicating higher levels of migration

See this image and copyright information in PMC

References

1. Plowe, C. V. The Danger of Untreatable Malaria is Real and Present. (Washington, DC, 2015).
1. World Health Organization. World Health Statistics 2016: Monitoring Health for the SDGs. (2016).
1. Tatem AJ, Smith DL. International population movements and regional Plasmodium falciparum malaria elimination strategies. Proc. Natl Acad. Sci. USA. 2010;107:12222–12227. doi: 10.1073/pnas.1002971107. - DOI - PMC - PubMed
1. Wesolowski A, et al. Quantifying the impact of human mobility on malaria. Science. 2012;338:267–270. doi: 10.1126/science.1223467. - DOI - PMC - PubMed
1. Buckee CO, Wesolowski A, Eagle NN, Hansen E, Snow RW. Mobile phones and malaria: modeling human and parasite travel. Travel Med. Infect. Dis. 2013;11:15–22. doi: 10.1016/j.tmaid.201212003. - DOI - PMC - PubMed

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[1] Plowe, C. V. The Danger of Untreatable Malaria is Real and Present. (Washington, DC, 2015).

[2] Plowe, C. V. The Danger of Untreatable Malaria is Real and Present. (Washington, DC, 2015).

[3] World Health Organization. World Health Statistics 2016: Monitoring Health for the SDGs. (2016).

[4] World Health Organization. World Health Statistics 2016: Monitoring Health for the SDGs. (2016).

[5] Tatem AJ, Smith DL. International population movements and regional Plasmodium falciparum malaria elimination strategies. Proc. Natl Acad. Sci. USA. 2010;107:12222–12227. doi: 10.1073/pnas.1002971107. - DOI - PMC - PubMed

[6] Tatem AJ, Smith DL. International population movements and regional Plasmodium falciparum malaria elimination strategies. Proc. Natl Acad. Sci. USA. 2010;107:12222–12227. doi: 10.1073/pnas.1002971107. - DOI - PMC - PubMed

[7] Wesolowski A, et al. Quantifying the impact of human mobility on malaria. Science. 2012;338:267–270. doi: 10.1126/science.1223467. - DOI - PMC - PubMed

[8] Wesolowski A, et al. Quantifying the impact of human mobility on malaria. Science. 2012;338:267–270. doi: 10.1126/science.1223467. - DOI - PMC - PubMed

[9] Buckee CO, Wesolowski A, Eagle NN, Hansen E, Snow RW. Mobile phones and malaria: modeling human and parasite travel. Travel Med. Infect. Dis. 2013;11:15–22. doi: 10.1016/j.tmaid.201212003. - DOI - PMC - PubMed

[10] Buckee CO, Wesolowski A, Eagle NN, Hansen E, Snow RW. Mobile phones and malaria: modeling human and parasite travel. Travel Med. Infect. Dis. 2013;11:15–22. doi: 10.1016/j.tmaid.201212003. - DOI - PMC - PubMed

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Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns

Collaborators

Affiliations

Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources