Skip to content
Clinical isolates of uncomplicated falciparum malaria from high and low malaria transmission areas show distinct pfcrt and pfmdr1 polymorphisms in western Ethiopia | Malaria Journal
WHO. Global report on antimalarial drug efficacy and drug resistance: 2000–2010. [Internet]. Geneva, World Health Organization; 2010. https://reliefweb.int/report/world/global-report-antimalarial-efficacy-and-drug-resistance-2000-2010?.
Menard D, Dondorp A. Antimalarial drug resistance: a threat to malaria elimination. Cold Spring Harb Perspect. 2017;7:a025619.
Google Scholar
Uwimana A, Legrand E, Stokes BH, Ndikumana JM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26:1602–8.
Google Scholar
Tumwebaze PK, Conrad MD, Okitwi M, Orena S, Byaruhanga O, Katairo T, et al. Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda. Nat Commun. 2022;3:6353.
Google Scholar
Awasthi G, Krishna BK, Das A. Pfcrt haplotypes and the evolutionary history of chloroquine-resistant Plasmodium falciparum. Mem Inst Oswaldo Cruz. 2012;107:129–34.
Google Scholar
Pelleau S, Moss EL, Dhingra SK, Volney B, Casteras J, Gabryszewski SJ, et al. Adaptive evolution of malaria parasites in French Guiana: reversal of chloroquine resistance by acquisition of a mutation in pfcrt. Proc Natl Acad Sci USA. 2015;112:11672–7.
Google Scholar
Kebede S, Aseffa A, Berhe N, Teklehaymanot T, Clouse RM, Gebru T, et al. Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia. Malar J. 2014;13:244.
Google Scholar
Kishoyian G, Njagi EN, Orinda GO, Kimani FT. Chloroquine sensitivity and prevalence of chloroquine-resistant genes pfcrt and pfmdr-1 in Western Kenya after two decades of chloroquine withdrawal. Ann Med Health Sci. 2018;8:331–5.
Omedo I, Bartilol B, Kimani D, Gonçalves S, Drury E, Rono MK, et al. Spatio-temporal distribution of antimalarial drug resistant gene mutations in a Plasmodium falciparum parasite population from Kilifi, Kenya: a 25-year retrospective study. Wellcome Open Res. 2022;7:1–21.
Google Scholar
Salissou A, Zamanka H, Binze BB, Rivière T, Tichit M, Ibrahim ML, et al. Low prevalence of pfcrt resistance alleles among patients with uncomplicated falciparum malaria in Niger six years after chloroquine withdrawal. Malar Res Treat. 2014;2014:614190.
Google Scholar
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, et al. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis. 2003;187:1870–5.
Google Scholar
Moyeh MN, Njimoh DL, Evehe MS, Ali IM, Nji AM, Nkafu DN, et al. Effects of drug policy changes on evolution of molecular markers of Plasmodium falciparum resistance to chloroquine, amodiaquine, and sulphadoxine-pyrimethamine in the South West Region of Cameroon. Malar Res Treat. 2018;2018:7071383.
Google Scholar
Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G. High prevalence of pfcrt-CVIET haplotype in isolates from asymptomatic and symptomatic patients in south-central Oromia. Ethiopia Malar J. 2014;13:120.
Google Scholar
Golassa L, Kamugisha E, Ishengoma DS, Baraka V, Shayo A, Baliraine FN, et al. Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania. Malar J. 2015;14:264.
Google Scholar
Hassen J, Solomon G, Dinka H, Golassa L. High prevalence of Pfcrt76T and Pfmdr1 N86 genotypes in malaria infected patients attending health facilities in East Shewa zone, Oromia Regional State, Ethiopia. Malar J. 2022;21:286.
Google Scholar
Hailemeskel E, Menberu T, Shumie G, Behaksra S, Chali W, Keffale M. Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia. Int J Parasitol Drugs Drug Resist. 2019;11:8–12.
Google Scholar
Roux AT, Maharaj L, Oyegoke O, Akoniyon OP, Adeleke MA, Maharaj R, et al. Chloroquine and sulfadoxine–pyrimethamine resistance in sub-Saharan Africa: a review. Front Genet. 2021;12:668574.
Google Scholar
Qidwai T. Exploration of copy number variation in genes related to anti-malarial drug resistance in Plasmodium falciparum. Gene. 2020;736:144414.
Google Scholar
Arya A, Kojom LP, Chaudhry S, Sharma A, Singh V. Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: a systematic review of clinical studies from two malaria endemic regions India and sub-Saharan Africa. Int J Parasitol Drugs Drug Resist. 2021;15:43–56.
Google Scholar
Ibraheem ZO, AbdMajid RA, Noor SM, Sedik HM, Basir R. Role of different Pfcrt and Pfmdr-1 mutations in conferring resistance to antimalaria drugs in Plasmodium falciparum. Malar Res Treat. 2014;2014:950424.
Google Scholar
Veiga MI, Dhingra SK, Henrich PP, Straimer J, Gnädig N, Uhlemann AC, et al. Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. Nat Commun. 2016;7:11553.
Google Scholar
Al-Mekhlafi HM, Madkhali AM, Ahmed A, Abdulhaq AA, Atroosh WM, Ghzwani AH, et al. Polymorphism analysis of pfmdr1gene in Plasmodium falciparum isolates 11 years post-adoption of artemisinin-based combination therapy in Saudi Arabia. Sci Rep. 2022;12:517.
Google Scholar
Okell LC, Reiter LM, Ebbe LS, Baraka V, Bisanzio D, Watson OJ, et al. Emerging implications of policies on malaria treatment: genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether–lumefantrine and artesunate–amodiaquine in Africa. BMJ Glob Health. 2018;3:e000999.
Google Scholar
Achieng AO, Muiruri P, Ingasia LA, Opot BH, Juma DW, Yeda R, et al. Temporal trends in prevalence of Plasmodium falciparum molecular markers selected for by artemether lumefantrine treatment in pre-ACT and post-ACT parasites in western Kenya. Int J Parasitol Drugs Drug Resist. 2015;5:92–9.
Google Scholar
Thomsen TT, Madsen LB, Hansson HH, Tomás EV, Charlwood D, Bygbjerg IC, et al. Rapid selection of Plasmodium falciparum chloroquine resistance transporter gene and multidrug resistance gene-1 haplotypes associated with past chloroquine and present artemether–lumefantrine use in Inhambane District, Southern Mozambique. Am J Trop Med Hyg. 2013;88:536–41.
Google Scholar
Heuchert A, Abduselam N, Zeynudin A, Eshetu T, Loscher T, Wieser A, et al. Molecular markers of anti-malarial drug resistance in southwest Ethiopia over time: regional surveillance from 2006 to 2013. Malar J. 2015;14:208.
Google Scholar
Shah NK, Alker AP, Sem R, Susanti AI, Muth S, Maguire JD, et al. Molecular surveillance for multidrug-resistant Plasmodium falciparum. Cambodia Emerg Infect Dis. 2008;14:1637–40.
Google Scholar
Srimuang K, Miotto O, Lim P, Fairhurst RM, Kwiatkowski DP, Woodrow CJ, et al. Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the tracking resistance to artemisinin collaboration. Malar J. 2016;15:541.
Google Scholar
Lim P, Alker AP, Khim N, Shah NK, Incardona S, Doung S, et al. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia. Malar J. 2009;8:11.
Google Scholar
Ngalah BS, Ingasia LA, Cheruiyot AC, Chebon LJ, Juma DW, Muiruri P, et al. Analysis of major genome loci underlying artemisinin resistance and pfmdr1 copy number in pre- and post-ACTs in Western Kenya. Sci Rep. 2013;5:8308.
Google Scholar
Gadalla NB, Adam I, Elzaki S, Bashi S, Mukhtar I, Oguike M, et al. Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether–lumefantrine. Antimicrob Agents Chemother. 2011;55:5408–11.
Google Scholar
Win AA, Imwong M, Kyaw MP, Woodrow CJ, Chotivanich K, Hanboonkunupakarn B, et al. K13 mutations and pfmdr1 copy number variation in Plasmodium falciparum malaria in Myanmar. Malar J. 2016;15:110.
Google Scholar
Labadie-Bracho M, Adhin MR. Increased pfmdr1 copy number in Plasmodium falciparum isolates from Suriname. Trop Med Int Health. 2013;18:796–9.
Google Scholar
Pacheco C, Moreno J, Herrera F. A high number of pfmdr1 gene copies in P. falciparum from Venezuela. Parasitol Res. 2019;118:3085–9.
Google Scholar
Tajebe A, Aemero M, Francis K, Magoma G. Identification of chloroquine resistance Pfcrt-K76T and determination of Pfmdr1-N86Y copy number by SYBR Green I qPCR. Asian Pac J Trop Biomed. 2015;5:208–20.
Google Scholar
UNHCR. Ethiopia Operation. Sherkole camp profile. [Internet]; 2020. https://data.unhcr.org/en/documents/details/83700.
Ministry of Health, Federal Democratic Republic of Ethiopia. An epidemiological profile of malaria in Ethiopia [Internet]. Addis Ababa, 2014. https://web-archive.lshtm.ac.uk/www.linkmalaria.org/sites/link/files/content/country/profiles/Ethiopia%20Epi%20Report%20(240314).pdf.
Taffese HS, Hemming-Schroeder E, Koepfli C, Tesfaye G, Lee MC, Kazura J, et al. Malaria epidemiology and interventions in Ethiopia from 2001 to 2016. Infect Dis Poverty. 2018;7:103.
Google Scholar
FMOH. Ethiopia Malaria elimination strategic plan: 2021–2025.
Dufera M, Kenea O, Tadele G. Malaria incidence and associated risk factors in and around Anger Gute Town. Western Ethiopia Res Square. 2020. https://doi.org/10.21203/rs.3.rs-29458/v1.
Google Scholar
Assefa A. The third Ethiopian Malaria indicator survey 2015. EMIS-2015.
WHO. Basic malaria microscopy. Geneva: World Health Organization; 2010.
Simon N, Shallat J, Williams C, Harrington WE. Optimization of Chelex 100 resin-based extraction of genomic DNA from dried blood spots. Biol Methods Protoc. 2020;5:bpaa009.
Google Scholar
Hofmann N, Mwingira F, Shekalaghe S, Robinson LJ, Mueller I, Felger I. Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets. PLoS Med. 2015;12:e1001788.
Google Scholar
Daniels R, Ndiaye D, Wall M, McKinney J, Séne PD, Sabeti PC, et al. Rapid, field-deployable method for genotyping and discovery of single-nucleotide polymorphisms associated with drug resistance in Plasmodium falciparum. Antimicrob Agents Chemother. 2012;56:2976–86.
Google Scholar
Nyang H. Copy number variation assay: ASSAY-MDEE-025. MRC Unit the Gambia at LSHTM.2021; Version: 1.0.
Schunk M, Kumma WP, Miranda IB, Osman ME, Roewer S, Alano A, et al. High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia. Malar J. 2006;5:54.
Google Scholar
Lo E, Hemming-Schroeder E, Yewhalaw D, Nguyen J, Kebede E, Zemene E, et al. Transmission dynamics of co-endemic Plasmodium vivax and P. falciparum in Ethiopia and prevalence of antimalarial resistant genotypes. PLoS Negl Trop Dis. 2017;11:e0005806.
Google Scholar
Talisuna AO, Okello PE, Erhart A, Coosemans M, Alessandro UD. Intensity of malaria transmission and the spread of Plasmodium falciparum—resistant malaria: a review of epidemiologic field evidence. Am J Trop Med Hyg. 2007;77:170–80.
Google Scholar
Masserey T, Lee T, Golumbeanu M, Shattock AJ, Kelly SL, Hastings IM, et al. The influence of biological, epidemiological, and treatment factors on the establishment and spread of drug resistant Plasmodium falciparum. Elife. 2022;11:e77634.
Google Scholar
Gida Ayana District Health Office. 2019/2020 Annual malaria report.
Benishangul-Gumuz Regional Health Bureau. 2019/2020 Annual malaria report.
Jalousian F, Dalimi A, Samiee SM, Ghaffarifar F, Soleymanloo F, Naghizadeh R. Mutation in pfmdr1 gene in chloroquine-resistant Plasmodium falciparum isolates, Southeast Iran. Int J Infect Dis. 2008;12:630–4.
Google Scholar
Gresty KJ, Gray K, Bobogare A, Taleo G, Hii J, Wini L, et al. Genetic mutations in pfcrt and pfmdr1 at the time of artemisinin combination therapy introduction in South Pacific islands of Vanuatu and Solomon Islands. Malar J. 2014;13:406.
Google Scholar
Plummer WB, Lexley LP, Carrington CV. Pfcrt and pfmdr1 alleles associated with Chloroquine resistance in Plasmodium falciparum from Guyana, South America. Mem Inst Oswaldo Cruz. 2004;99:389–92.
Google Scholar
Sidhu AB, Valderramos SG, Fidock DA. Pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol Microbiol. 2005;57:913–26.
Google Scholar
Achol E, Ochaya S, Malinga GM, Edema H, Echodu R. High prevalence of Pfmdr1 N86 and D1246 genotypes detected among febrile malaria outpatients attending Lira Regional Referral Hospital, Northern Uganda. BMC Res Notes. 2019;12:235.
Google Scholar
Voumbo-Matoumona DF, Kouna LC, Madamet M, Maghendji-Nzondo S, Pradines B, Lekana-Douki JB. Prevalence of Plasmodium falciparum antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014. Infect Drug Resist. 2018;11:1329–38.
Google Scholar
Duah NO, Matrevi SA, Souza DK, Binnah DD, Tamakloe MM, Opoku VS, et al. Increased pfmdr1 gene copy number and the decline in pfcrt and pfmdr1 resistance alleles in Ghanaian Plasmodium falciparum isolates after the change of anti-malarial drug treatment policy. Malar J. 2013;12:377.
Google Scholar
Tadele G, Jaiteh FK, Oboh M, Oriero E, Dugassa S, Amambua-Ngwa A, et al. Persistence of residual submicroscopic P. falciparum parasitemia following treatment of artemether–lumefantrine in Ethio-Sudan Border, Western Ethiopia. Antimicrob Agents Chemother. 2022;66:e0000222.
Google Scholar
Chaisatit C, Sai-Ngam P, Thaloengsok S, Sriwichai S, Jongsakul K, Fukuda M, et al. Molecular detection of mutations in the propeller domain of kelch 13 and pfmdr1 copy number variation in Plasmodium falciparum isolates from Thailand collected from 2002 to 2007. Am J Trop Med Hyg. 2021;105:1093–6.
Google Scholar
