Plasmodium falciparum Multidrug Resistance-1 (pfmdr1) Gene Mutation in Adults Malaria Patients Attending Murtala Muhammad Specialist Hospital Kano, Northwest Nigeria
DOI:
https://doi.org/10.54987/jobimb.v11i1.803Abstract
Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine in Kano state northwestern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) gene. Hundred adult patients comprising 43 males and 57 females were recruited for the study. The mean age of participants is 36.4 years, minimum and maximum ages were 16 and 60 years respectively, while 41% of them fall within the range of 16 to 30 years. Blood isolates were then analyzed for the presence of malaria parasite using microscopy, the results show a high prevalence of P. falciparum infection in the subject (30%). Pfmdr1 gene, a molecular marker of artemisinin resistance, was successfully sequenced in 21 out of 100 P. falciparum isolates collected from recruited participants. Pfmdr1 mutations were found in 19.5% (4/33) of the samples isolated. The prevalence of the Pfmdr1 N86Y allele was found in 4 samples whilst Y184F and D1246Y were not detected. A total of 4 non-synonymous mutations at codon N86Y were detected. The presence of these mutations highlights the challenges for malaria treatment in Kano state, northwestern Nigeria using antimalarials such as artemether lumefantrine, mefloquine, amodiaquine quinine and lumefantrine.
References
Roll Back Malaria Research Group. International Federation of Red Cross and Red Crescent Societies. Optimizing control of infectious diseases in resource-poor countries: Malaria diagnosis, fever home-based management and new tools. Brussels, Belgium. 2020 Available at: http://www.rbm.who.int/globaladvocacy.
WHO. World Malaria Report 2018; WHO: Geneva, Switzerland; 2018
WHO. Global malaria programme. World malaria report. Geneva, Switzerland; 2020. Available at: http:// www.who.int/malaria
Gorobets NY, Sedash YV, Singh BK, Poonam RB. An overview of currently available antimalarials. Curr Top Med Chem (2017);17:2143-2157. https://doi.org/10.2174/1568026617666170130123520.
Phillips MA, Burrows JN, Manyando C, Huijsduijnen RH, Voorhis WC, Van Wells TNC. Malaria. Nature Rev. (2017);50:24-37. http://doi.org/10.1038/nrdp.50
Thriemer K, Ley B, Bobogare A, Dysoley L, Alam MS, Pasaribu AP, Sattabongkot J, Jambert E, Domingo GJ, Commons R, Auburn S, Marfurt J, Devine A, Aktaruzzaman MM, Sohel N, Namgay R, Drukpa T, Sharma SN, Sarawati E, Samad I, Theodora M, Nambanya S, Ounekham S, Mudin RB, Da Thakur G, Makita LS, Deray R, Lee SE, Boaz L, Danansuriya MN, Mudiyanselage SD, Chinanonwait N, Kitchakarn S, Nausien J, Naket E, Duc TN, Do Manh H, Hong YS, Cheng Q, Richards JS, Kusriastuti R, Satyagraha A, Noviyanti R, Ding XC, Khan WA, Swe Phru C, Guoding Z, Qi G, Kaneko A, Miotto O, Nguitragool W, Roobsoong W, Battle K, Howes RE, Roca-Feltrer A, Duparc S, Bhowmick IP, Kenangalem E, Bibit JA, Barry A, Sintasath D, Abeyasinghe R, Sibley CH, McCarthy J, von Seidlein L, Baird JK, Price RN. Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group. Malaria J. (2017);16:141. https://doi.org/10.1186/s12936-017-1784-1.
Fairhurst RM, Dondorp AM. Artemisinin-resistant Plasmodium falciparum malaria. Microbiol Spectr 4. (2016);EI10-0013. https://doi.org/10.1128/microbiolspec.
Weiss DJ, Lucas TCD, Nguyen M, Nandi AK, Bisanzio D, Battle KE, Cameron E, Twohig K A and Pfeffer DA. Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000-17: a spatial and temporal modelling study. The Lancet. (2019);394 (10195): 322-331.
Bonnet M., Van Den Broek I., Van Herp M., Urrutia P.P., Van Overmeir C., Kyomuhendo J (2009). The Journal of Clinical Investigation http://www.jci.org Volume?118 Number?4
Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, Vanichtanankul J, Sirawaraporn W, Taylor P, Walkinshaw MD, Yuthavong Y. Nat. Struct. Biol. 2013; 10:357-365.
Apinjoh TO, Mugri RN, Miotto O, Chi HF, Tata RB, Anchang-Kimbi JK. Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of Mount Cameroon: Cross-sectional study. Infectious Diseases of Poverty 2017; 6(1):136.
Cheesbrough M. District laboratory practice in tropical countries, part 1 2nd edition, Cambridge University Press, Cambridge. 2005; Page 178- 208.
Basco LK, Bras JL, Rhoades Z and Wilson CM. Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from Subsaharan Africa. Mol Biochem Parasitol. (1995)74(2):157-166.
FMOH (2005). Federal Republic of Nigeria National Antimalarial Treatment Federal Ministry of Health, (February).
Margaret I, Ilomuanya MO, Kalu C, Nnakebe C, and Achonu LC. Survey of First line theraphy for uncomplicated malaria in compliance with malaria policy change in a faith Based hosipital in Lagos Nigeria. World J. Pharmaceut. Res. 2012;1(2): 1-9.
Thanh NV, Nhien NT, Thi N, Tuyen K, Tong NT, Thuy N, Hien TT. Rapid decline in the susceptibility of Plasmodium falciparum to dihydroartemisinin - piperaquine in the south of Vietnam. Malaria J. 2017;1-10. http://doi.org/10.1186/s12936.
Nyunt MH, Hlaing T, Oo HW, Tin-oo LK, Phway HP, Wang B, Han E. Molecular Assessment of Artemisinin Resistance Markers , Polymorphisms in the K13 Propeller , and a Multidrug-Resistance Gene in the Eastern and Western Border Areas of Myanmar. Asian J..Mol..Biol..2015;60:1208-1215. http://doi.org/10.1093/cid/ciu1160
Zaid OI, AbdulMajid R, Mohd S, Mohd HS, Basir R. Review Article Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum. Malaria Res Treat. 2014;1-17 http://dx.doi.org/10.1155/2014/950424
Ayogu EE, Ukwe CV, Mgbeahurike AC and Nna EO. Prevalence of Pfmdr1 86y and 184f Alleles is Associated with Recurrent Parasitemia Following Treatment of Uncomplicated Malaria with Artemether-Lumefantrine in Nigerian Patients. J App Pharm Sci. 2016;66(04): 015-021.
Sowunmi A, Akano K, Ntadom G, Happi CT. Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments. Infect Dis Poverty. 2017;6:36.
Auwal A, Mahmoud SJ, Hauwa MS, Bassa OY, Mohammed AI., Emmanuel OB, Daniel KI, Kiyoshi K. Plasmodium falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the Continued Use of Artemether-Lumefantrine in the Region. Malaria J. 2017;1:474-77. DOI: https://doi.org/10.21203/rs.3.rs
Kaewpruk N, Tan-ariya P, Ward S, Sitthichot N, Suwandittakul N, Mungthin M. Pfmdr1 polymorphisms infuence on in vitro sensitivity of Thai Plasmodium falciparum isolates to primaquine, sitamaquine and tafenoquine. Southeast Asian J Trop Med Public Health. 2016;47:366-76.
Veiga MI, Dhingra SK, Henrich PP, Straimer J, Gnädig N, Uhlemann AC. Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. Nat. Commun. 2016;77:1-12.
Gil JP, Krishna S. Pfmdr1 (Plasmodium falciparum multidrug drug resistance gene 1): a pivotal factor in malaria resistance to artemisinin combination therapies. Expert Rev Anti Infect Ther. 2017;15:527-43.
Atroosh WM, Al-Mekhlafi HM, Mahdy MAK, and Surin J. The detection of pfcrt and pfmdr1 point mutations as molecular markers of chloroquine drug resistance, Pahang, Malaysia. Malaria J. 2012;11(251): 32.
Olasehinde GI, Ojurongbe DO, Akinjogunla OJ, Egwari LO, Adeyeba AO. Prevalence of malaria and predisposing factors to antimalarial drug resistance in southwestern Nigeria. Res J Parasitol. 2014; 10: 92-101.
Shrivastava SK, Gupta RK, Mahanta J, Dubey ML. Correlation of molecular markers, Pfmdr1-N86Y and Pfcrt-K76T, with in vitro chloroquine resistant Plasmodium falciparum, isolated in the malaria endemic states of assam and arunachal Pradesh, Northeast India. PLoS ONE. 2014; 9:1038-48.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Journal of Biochemistry, Microbiology and Biotechnology
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).