The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC

Robert Verity; Ozkan Aydemir; Nicholas F. Brazeau; Oliver J. Watson; Nicholas J. Hathaway; Melchior Kashamuka Mwandagalirwa; Patrick W. Marsh; Kyaw Thwai; Travis Fulton; Madeline Denton; Andrew P. Morgan; Jonathan B. Parr; Patrick K. Tumwebaze; Melissa Conrad; Philip J. Rosenthal; Deus S. Ishengoma; Jeremiah Ngondi; Julie Gutman; Modest Mulenga; Douglas E. Norris; William J. Moss; Benedicta A. Mensah; James L. Myers-Hansen; Anita Ghansah; Antoinette K. Tshefu; Azra C. Ghani; Steven R. Meshnick; Jeffrey A. Bailey; Jonathan J. Juliano

doi:10.1038/s41467-020-15779-8

The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC

Robert Verity, Ozkan Aydemir, Nicholas F. Brazeau, Oliver J. Watson, Nicholas J. Hathaway, Melchior Kashamuka Mwandagalirwa, Patrick W. Marsh, Kyaw Thwai, Travis Fulton, Madeline Denton, Andrew P. Morgan, Jonathan B. Parr, Patrick K. Tumwebaze, Melissa Conrad, Philip J. Rosenthal, Deus S. Ishengoma, Jeremiah Ngondi, Julie Gutman, Modest Mulenga, Douglas E. NorrisWilliam J. Moss, Benedicta A. Mensah, James L. Myers-Hansen, Anita Ghansah, Antoinette K. Tshefu, Azra C. Ghani, Steven R. Meshnick, Jeffrey A. Bailey, Jonathan J. Juliano

Department of Parasitology

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

48 Citations (Scopus)

Abstract

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

Original language	English
Article number	2107
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15779-8
Publication status	Published - 1 Dec 2020

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Verity, R., Aydemir, O., Brazeau, N. F., Watson, O. J., Hathaway, N. J., Mwandagalirwa, M. K., Marsh, P. W., Thwai, K., Fulton, T., Denton, M., Morgan, A. P., Parr, J. B., Tumwebaze, P. K., Conrad, M., Rosenthal, P. J., Ishengoma, D. S., Ngondi, J., Gutman, J., Mulenga, M., ... Juliano, J. J. (2020). The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC. Nature Communications, 11(1), Article 2107. https://doi.org/10.1038/s41467-020-15779-8

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title = "The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC",

abstract = "The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.",

author = "Robert Verity and Ozkan Aydemir and Brazeau, {Nicholas F.} and Watson, {Oliver J.} and Hathaway, {Nicholas J.} and Mwandagalirwa, {Melchior Kashamuka} and Marsh, {Patrick W.} and Kyaw Thwai and Travis Fulton and Madeline Denton and Morgan, {Andrew P.} and Parr, {Jonathan B.} and Tumwebaze, {Patrick K.} and Melissa Conrad and Rosenthal, {Philip J.} and Ishengoma, {Deus S.} and Jeremiah Ngondi and Julie Gutman and Modest Mulenga and Norris, {Douglas E.} and Moss, {William J.} and Mensah, {Benedicta A.} and Myers-Hansen, {James L.} and Anita Ghansah and Tshefu, {Antoinette K.} and Ghani, {Azra C.} and Meshnick, {Steven R.} and Bailey, {Jeffrey A.} and Juliano, {Jonathan J.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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doi = "10.1038/s41467-020-15779-8",

language = "English",

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Verity, R, Aydemir, O, Brazeau, NF, Watson, OJ, Hathaway, NJ, Mwandagalirwa, MK, Marsh, PW, Thwai, K, Fulton, T, Denton, M, Morgan, AP, Parr, JB, Tumwebaze, PK, Conrad, M, Rosenthal, PJ, Ishengoma, DS, Ngondi, J, Gutman, J, Mulenga, M, Norris, DE, Moss, WJ, Mensah, BA, Myers-Hansen, JL, Ghansah, A, Tshefu, AK, Ghani, AC, Meshnick, SR, Bailey, JA & Juliano, JJ 2020, 'The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC', Nature Communications, vol. 11, no. 1, 2107. https://doi.org/10.1038/s41467-020-15779-8

TY - JOUR

T1 - The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC

AU - Verity, Robert

AU - Aydemir, Ozkan

AU - Brazeau, Nicholas F.

AU - Watson, Oliver J.

AU - Hathaway, Nicholas J.

AU - Mwandagalirwa, Melchior Kashamuka

AU - Marsh, Patrick W.

AU - Thwai, Kyaw

AU - Fulton, Travis

AU - Denton, Madeline

AU - Morgan, Andrew P.

AU - Parr, Jonathan B.

AU - Tumwebaze, Patrick K.

AU - Conrad, Melissa

AU - Rosenthal, Philip J.

AU - Ishengoma, Deus S.

AU - Ngondi, Jeremiah

AU - Gutman, Julie

AU - Mulenga, Modest

AU - Norris, Douglas E.

AU - Moss, William J.

AU - Mensah, Benedicta A.

AU - Myers-Hansen, James L.

AU - Ghansah, Anita

AU - Tshefu, Antoinette K.

AU - Ghani, Azra C.

AU - Meshnick, Steven R.

AU - Bailey, Jeffrey A.

AU - Juliano, Jonathan J.

PY - 2020/12/1

Y1 - 2020/12/1

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AB - The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

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U2 - 10.1038/s41467-020-15779-8

DO - 10.1038/s41467-020-15779-8

M3 - Article

C2 - 32355199

AN - SCOPUS:85084149566

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2107

ER -

The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC

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