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

被引:48
|
作者
Verity, Robert [1 ]
Aydemir, Ozkan [2 ]
Brazeau, Nicholas F. [3 ]
Watson, Oliver J. [1 ]
Hathaway, Nicholas J. [4 ]
Mwandagalirwa, Melchior Kashamuka [5 ]
Marsh, Patrick W. [2 ]
Thwai, Kyaw [3 ]
Fulton, Travis [6 ]
Denton, Madeline [6 ]
Morgan, Andrew P. [6 ]
Parr, Jonathan B. [6 ]
Tumwebaze, Patrick K. [7 ]
Conrad, Melissa [8 ]
Rosenthal, Philip J. [8 ]
Ishengoma, Deus S. [9 ]
Ngondi, Jeremiah [10 ]
Gutman, Julie [11 ]
Mulenga, Modest [12 ]
Norris, Douglas E. [13 ]
Moss, William J. [14 ]
Mensah, Benedicta A. [15 ]
Myers-Hansen, James L. [15 ]
Ghansah, Anita [15 ]
Tshefu, Antoinette K. [5 ]
Ghani, Azra C. [1 ]
Meshnick, Steven R. [3 ]
Bailey, Jeffrey A. [2 ]
Juliano, Jonathan J. [3 ,6 ,16 ]
机构
[1] Imperial Coll London, Dept Infect Dis Epidemiol, Med Res Council, Ctr Global Infect Dis Anal, London, England
[2] Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02912 USA
[3] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA
[4] Univ Massachusetts, Program Bioinformat & Integrat Biol, Worcester, MA 01605 USA
[5] Hop Gen Prov Reference Kinshasa, Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO
[6] Univ N Carolina, Sch Med, Div Infect Dis, Dept Med, Chapel Hill, NC 27515 USA
[7] Infect Dis Res Collaborat, Kampala, Uganda
[8] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[9] Natl Inst Med Res, Tanga, Tanzania
[10] RTI Int, Dar Es Salaam, Tanzania
[11] CDC, Malaria Branch, Ctr Global Hlth, Atlanta, GA 30333 USA
[12] Trop Dis Res Ctr, Ndola, Zambia
[13] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA
[14] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
[15] Univ Ghana, Noguchi Mem Inst Med Res, Accra, Ghana
[16] Univ N Carolina, Sch Med, Curriculum Genet & Mol Biol, Chapel Hill, NC 27515 USA
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
F-STATISTICS; R PACKAGE; DIVERSITY; FRAMEWORK; SELECTION; MALARIA; REHH;
D O I
10.1038/s41467-020-15779-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population.
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页数:10
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