Genome-wide Genetic Variation and Molecular Surveillance of Drug Resistance in Plasmodium Falciparum Isolates from Asymptomatic Individuals in Ouélessébougou, Mali

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jun 12

PMID 37308503

Authors

Leen N Vanheer

Almahamoudou Mahamar

Emilia Manko

Sidi M Niambele

Koualy Sanogo

Ahamadou Youssouf

Adama Dembele

Makonon Diallo

Seydina O Maguiraga

Jody Phelan

Ashley Osborne

Anton Spadar

Merel J Smit

Teun Bousema

Chris Drakeley

Taane G Clark

William Stone

Alassane Dicko

Susana Campino

Affiliations

Soon will be listed here.

Abstract

Sequence analysis of Plasmodium falciparum parasites is informative in ensuring sustained success of malaria control programmes. Whole-genome sequencing technologies provide insights into the epidemiology and genome-wide variation of P. falciparum populations and can characterise geographical as well as temporal changes. This is particularly important to monitor the emergence and spread of drug resistant P. falciparum parasites which is threatening malaria control programmes world-wide. Here, we provide a detailed characterisation of genome-wide genetic variation and drug resistance profiles in asymptomatic individuals in South-Western Mali, where malaria transmission is intense and seasonal, and case numbers have recently increased. Samples collected from Ouélessébougou, Mali (2019-2020; n = 87) were sequenced and placed in the context of older Malian (2007-2017; n = 876) and African-wide (n = 711) P. falciparum isolates. Our analysis revealed high multiclonality and low relatedness between isolates, in addition to increased frequencies of molecular markers for sulfadoxine-pyrimethamine and lumefantrine resistance, compared to older Malian isolates. Furthermore, 21 genes under selective pressure were identified, including a transmission-blocking vaccine candidate (pfCelTOS) and an erythrocyte invasion locus (pfdblmsp2). Overall, our work provides the most recent assessment of P. falciparum genetic diversity in Mali, a country with the second highest burden of malaria in West Africa, thereby informing malaria control activities.

References

Veiga M, Dhingra S, Henrich P, Straimer J, Gnadig N, Uhlemann A . Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. Nat Commun. 2016; 7:11553. PMC: 4873939. DOI: 10.1038/ncomms11553. View

Tadesse F, Slater H, Chali W, Teelen K, Lanke K, Belachew M . The Relative Contribution of Symptomatic and Asymptomatic Plasmodium vivax and Plasmodium falciparum Infections to the Infectious Reservoir in a Low-Endemic Setting in Ethiopia. Clin Infect Dis. 2018; 66(12):1883-1891. DOI: 10.1093/cid/cix1123. View

Taylor A, Flegg J, Holmes C, Guerin P, Sibley C, Conrad M . Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine Exert Inverse Selective Pressure on Drug Sensitivity-Associated Haplotypes in Uganda. Open Forum Infect Dis. 2017; 4(1):ofw229. PMC: 5413987. DOI: 10.1093/ofid/ofw229. View

Hamid M, Abdelraheem M, Acheampong D, Ahouidi A, Ali M, Almagro-Garcia J . Pf7: an open dataset of genome variation in 20,000 worldwide samples. Wellcome Open Res. 2023; 8:22. PMC: 9971654. DOI: 10.12688/wellcomeopenres.18681.1. View

Caye K, Deist T, Martins H, Michel O, Francois O . TESS3: fast inference of spatial population structure and genome scans for selection. Mol Ecol Resour. 2015; 16(2):540-8. DOI: 10.1111/1755-0998.12471. View

Abera D, Kibet C, Degefa T, Amenga-Etego L, Bargul J, Golassa L . Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia. Malar J. 2021; 20(1):129. PMC: 7934276. DOI: 10.1186/s12936-021-03660-y. View

Osborne A, Manko E, Takeda M, Kaneko A, Kagaya W, Chan C . Characterizing the genomic variation and population dynamics of Plasmodium falciparum malaria parasites in and around Lake Victoria, Kenya. Sci Rep. 2021; 11(1):19809. PMC: 8494747. DOI: 10.1038/s41598-021-99192-1. View

Minh B, Schmidt H, Chernomor O, Schrempf D, Woodhams M, von Haeseler A . IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era. Mol Biol Evol. 2020; 37(5):1530-1534. PMC: 7182206. DOI: 10.1093/molbev/msaa015. View

Dagnogo O, Ako A, Ouattara L, Dago N, Ngolo Coulibaly D, Toure A . Towards a re-emergence of chloroquine sensitivity in Côte d'Ivoire?. Malar J. 2018; 17(1):413. PMC: 6223040. DOI: 10.1186/s12936-018-2551-7. View

10.

Njiro B, Mutagonda R, Chamani A, Mwakyandile T, Sabas D, Bwire G . Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review. J Infect Public Health. 2022; 15(5):550-557. DOI: 10.1016/j.jiph.2022.03.015. View

11.

Oyola S, Ariani C, Hamilton W, Kekre M, Amenga-Etego L, Ghansah A . Whole genome sequencing of Plasmodium falciparum from dried blood spots using selective whole genome amplification. Malar J. 2016; 15(1):597. PMC: 5175302. DOI: 10.1186/s12936-016-1641-7. View

12.

Cissoko M, Sagara I, Sankare M, Dieng S, Guindo A, Doumbia Z . Geo-Epidemiology of Malaria at the Health Area Level, Dire Health District, Mali, 2013-2017. Int J Environ Res Public Health. 2020; 17(11). PMC: 7312793. DOI: 10.3390/ijerph17113982. View

13.

Stokes B, Dhingra S, Rubiano K, Mok S, Straimer J, Gnadig N . K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness. Elife. 2021; 10. PMC: 8321553. DOI: 10.7554/eLife.66277. View

14.

Pfeffer D, Lucas T, May D, Harris J, Rozier J, Twohig K . malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project. Malar J. 2018; 17(1):352. PMC: 6173876. DOI: 10.1186/s12936-018-2500-5. View

15.

Ocholla H, Preston M, Mipando M, Jensen A, Campino S, MacInnis B . Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J Infect Dis. 2014; 210(12):1991-2000. PMC: 4241944. DOI: 10.1093/infdis/jiu349. View

16.

Clarke E, Sundararaman S, Seifert S, Bushman F, Hahn B, Brisson D . swga: a primer design toolkit for selective whole genome amplification. Bioinformatics. 2017; 33(14):2071-2077. PMC: 5870857. DOI: 10.1093/bioinformatics/btx118. View

17.

Uwimana A, Legrand E, Stokes B, Ndikumana J, Warsame M, Umulisa N . Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020; 26(10):1602-1608. PMC: 7541349. DOI: 10.1038/s41591-020-1005-2. View

18.

Asare K, Africa J, Mbata J, Opoku Y . The emergence of chloroquine-sensitive Plasmodium falciparum is influenced by selected communities in some parts of the Central Region of Ghana. Malar J. 2021; 20(1):447. PMC: 8620919. DOI: 10.1186/s12936-021-03985-8. View

19.

Diakite S, Traore K, Sanogo I, Clark T, Campino S, Sangare M . A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali. Malar J. 2019; 18(1):361. PMC: 6849310. DOI: 10.1186/s12936-019-2986-5. View

20.

Bergmann-Leitner E, Hosie H, Trichilo J, DeRiso E, Ranallo R, Alefantis T . Self-adjuvanting bacterial vectors expressing pre-erythrocytic antigens induce sterile protection against malaria. Front Immunol. 2013; 4:176. PMC: 3701146. DOI: 10.3389/fimmu.2013.00176. View