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Suleiman Jada M, Umar Y, Abdullahi Pela A, Adamu A, Ahmed Zailani H, Usman Wurochekke A. Molecular surveillance of artemisinin resistance-linked PFK13 gene polymorphisms in Adamawa State, Nigeria. Journal of Research in Applied and Basic Medical Sciences 2025; 11 (1) :75-84
URL: http://ijrabms.umsu.ac.ir/article-1-391-en.html
Department of Biochemistry, Faculty of Life Sciences, Modibbo Adama University, Yola, Adamawa state, Nigeria , jadasm84@gmail.com
Abstract:   (91 Views)
Background & aims: The evolution and spread of Plasmodium falciparum malaria parasite capable of evading antimalarials, particularly artemisinin (ART), is a prime concern for malaria control. Mutations in the P. falciparum Kelch 13 (Pfk13) gene confer resistance to artemisinin, necessitating molecular surveillance of Pfk13 mutations. This study is aimed at investigating artemisinin resistance linked Pfk13-propeller polymorphisms in clinical isolates of P. falciparum from three Local Government Areas (Yola North, Numan and Mubi North), of Adamawa State, Nigeria.
Materials & methods: A total of 240 symptomatic malaria patients were recruited for this study. Eighty febrile patients diagnosed with uncomplicated P. falciparum malaria attending two major selected healthcare facilities in each of the three Local Government Areas were used. P. falciparum parasite was identified by Rapid Diagnostic Tests (RDTs) and Microscopy. DNA extraction and nested PCR were performed on positive samples to amplify the Pfk13 propeller domain. Sequencing and sequence analysis were conducted to check for mutations at validated codon positions.  
Results: Out of the 240 samples collected, RDT revealed 100% to be positive for P. falciparum while microscopy confirmed P. falciparum presence in 214 samples (89.17%). Extraction and amplification of Pfk13 gene were successful in 163 samples (67.92%). Out of 163 successfully amplified samples, no validated mutations linked to artemisinin resistance were found, but the A578S mutation was detected in 15.09% of the analyzed samples.
Conclusion: The absence of Pfk13 gene mutations indicates the sensitivity of the parasites in this study location to artemisinin treatments, but the mutant A578S observed needs to be investigated to determine its functional relevance in the Pfk13 propeller-domain. However, continuous surveillance and research are crucial to maintain these successes and address any future challenges posed by drug resistance.
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Type of Study: orginal article | Subject: Parasitology

References
1. World Health Organization (WHO). World malaria report 2020: 20 years of global progress and challenges. WHO; 2020. [URL]
2. Maiga FO, Wele M, Toure SM, Keita M, Tangara CO, Refeld RR, et al. Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Mali: a systematic review and meta-analysis. Malar. J 2021;20(1). [DOI:10.1186/s12936-021-03890-0] [PMID] [PMCID]
3. Dhorda M, Amaratunga C, Dondorp AM. Artemisinin and multidrug-resistant Plasmodium falciparum - a threat for malaria control and elimination. Curr Opin Infect Dis 2021;34(5):432-9. https://doi.org/10.1097/QCO.0000000000000766 [DOI:10.1097/qco.0000000000000766] [PMID] [PMCID]
4. Okebe J, Mwesigwa J, Kama EL, Ceesay SJ, Njie F, Correa S, et al. A comparative case control study of the determinants of clinical malaria in The Gambia. Malar. J 2014;13(1). [DOI:10.1186/1475-2875-13-306] [PMID] [PMCID]
5. Dong Y, Wang J, Sun A, Deng Y, Chen M, Xu Y, et al. Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China. Malar J 2018;17(1). [DOI:10.1186/s12936-018-2619-4] [PMID] [PMCID]
6. World Health Organization (WHO). World Malaria Report 2019. 2019. [URL]
7. Nyaaba N, Andoh NE, Amoh G, Amuzu DSY, Ansong M, Ordóñez-Mena JM, et al. Comparative efficacy and safety of the artemisinin derivatives compared to quinine for treating severe malaria in children and adults: A systematic update of literature and network meta-analysis. PLoS ONE 2022; 17(7):e0269391. [DOI:10.1371/journal.pone.0269391] [PMID] [PMCID]
8. Straimer J, Gnädig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, et al. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. J. Sci 2014;347(6220):428-31. [DOI:10.1126/science.1260867] [PMID] [PMCID]
9. Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nat 2013;505(7481):50-5. [DOI:10.1038/nature12876] [PMID] [PMCID]
10. Abubakar UF, Adam R, Mukhtar MM, Muhammad A, Yahuza AA, Ibrahim SS. Identification of Mutations in Antimalarial Resistance Gene Kelch 13 from Plasmodium falciparum Isolates in Kano, Nigeria. Trop. med. infect 2020;5(2):85. [DOI:10.3390/tropicalmed5020085] [PMID] [PMCID]
11. Uwimana A, Legrand E, Stokes BH, Ndikumana JLM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum Kelch 13 R561H mutant parasites in Rwanda. Nat. Med 2020;26(10):1602-8. [DOI:10.1038/s41591-020-1005-2] [PMID] [PMCID]
12. Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nat 2015;526(7572):207-11. [DOI:10.1038/nature15535] [PMID] [PMCID]
13. Chebore W, Zhou Z, Westercamp N, Otieno K, Shi YP, Sergent SB, et al. Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya. Malar. J 2020;19(1). [DOI:10.1186/s12936-020-03358-7] [PMID] [PMCID]
14. Dafalla OM, Alzahrani M, Sahli A, Helal MAA, Alhazmi MM, Noureldin EM, et al. Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia. Malar J 2020;19(1):1483. [DOI:10.1186/s12936-020-03467-3] [PMID] [PMCID]
15. Madkhali AM, Ghzwani AH, Al-Mekhlafi HM. Comparison of Rapid Diagnostic Test, Microscopy, and Polymerase Chain Reaction for the Detection of Plasmodium falciparum Malaria in a Low-Transmission Area, Jazan Region, Southwestern Saudi Arabia. Diagnostics 2022;12(6):1485. [DOI:10.3390/diagnostics12061485] [PMID] [PMCID]
16. Dahal P, Khanal B, Rai K, Kattel V, Yadav S, Bhattarai NR. Challenges in Laboratory Diagnosis of Malaria in a Low-Resource Country at Tertiary Care in Eastern Nepal: A Comparative Study of Conventional vs. Molecular Methodologies. J. Trop. Med 2021:1-9. [DOI:10.1155/2021/3811318] [PMID] [PMCID]
17. Ménard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, et al. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. N Engl J Med 2016; 374(25):2453-64. https://doi.org/10.1056/NEJMoa1513137 [DOI:10.1056/nejmoa1513137] [PMID] [PMCID]
18. Kamau E, Campino S, Amenga-Etego L, Drury E, Ishengoma D, Johnson K, et al. K13-Propeller Polymorphisms in Plasmodium falciparum Parasites from Sub-Saharan Africa. J. Infect. Dis 2014. [DOI:10.1093/infdis/jiu608] [PMID] []
19. Muhammad I, Sale P, Salisu M, Muhammad T, Abubakar B, Maidala A, et al. Molecular analysis of Bio-makers of Chloroquine resistance in Plasmodium falciparum Isolate from Gombe Local Government Area, Gombe State, Nigeria. Cell. Mol. Biomed. Rep 2022;2(1):42-55. [DOI:10.55705/cmbr.2022.335753.1033]
20. Igbasi U, Oyibo W, Omilabu S, Quan H, Chen S, Shen H, et al. Kelch 13 propeller gene polymorphism among Plasmodium falciparum isolates in Lagos, Nigeria: Molecular Epidemiologic Study. Trop. Med. Int. Health 2019;24(8):1011-7. [DOI:10.1111/tmi.13273] [PMID]
21. Ajogbasile FV, Oluniyi PE, Kayode AT, Akano KO, Adegboyega BB, Philip C, et al. Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria. PLoS ONE 2022;17(2):e0264548. [DOI:10.1371/journal.pone.0264548] [PMID] [PMCID]
22. Oboh MA, Ndiaye D, Antony HA, Badiane AS, Singh US, Ali NA, et al. Status of Artemisinin Resistance in Malaria Parasite Plasmodium falciparum from Molecular Analyses of the Kelch 13 Gene in Southwestern Nigeria. Biomed Res. Int 2018;2018:1-5. [DOI:10.1155/2018/2305062] [PMID] []
23. Gansané A, Moriarty LF, Ménard D, Yerbanga I, Ouedraogo E, Sondo P, et al. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018. Malar. J 2021;20(1). [DOI:10.1186/s12936-021-03585-6] [PMID] [PMCID]
24. Matrevi SA, Tandoh KZ, Bruku S, Opoku-Agyeman P, Adams T, Ennuson NA, et al. Novel pfk13 polymorphisms in Plasmodium falciparum population in Ghana. Sci. Rep 2022;12(1). [DOI:10.1038/s41598-022-11790-9] [PMID] [PMCID]
25. Ikeda M, Kaneko M, Tachibana SI, Balikagala B, Sakurai-Yatsushiro M, Yatsushiro S, et al. Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014-2016. Emerg. Infect. Dis 2018;24(4):718-26. [DOI:10.3201/eid2404.170141] [PMID] [PMCID]
26. De Laurent ZR, Chebon LJ, Ingasia LA, Akala HM, Andagalu B, Ochola-Oyier LI, et al. Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya. Am J Trop Med Hyg 2018;98(5):1360-6. [DOI:10.4269/ajtmh.17-0505] [PMID] [PMCID]
27. Lê HG, Naw H, Kang JM, Võ TC, Myint MK, Htun ZT, et al. Molecular Profiles of Multiple Antimalarial Drug Resistance Markers in Plasmodium falciparum and Plasmodium vivax in the Mandalay Region, Myanmar. Microorganisms 2022;10(10):2021. [DOI:10.3390/microorganisms10102021] [PMID] [PMCID]
28. Hawkes M, Conroy AL, Opoka RO, Namasopo S, Zhong K, Liles WC, et al. Slow Clearance of Plasmodium falciparum in Severe Pediatric Malaria, Uganda, 2011-2013. Emerg. Infect. Dis 2015;21(7):1237-9. [DOI:10.3201/eid2107.150213] [PMID] [PMCID]
29. Ndwiga L, Kimenyi KM, Wamae K, Osoti V, Akinyi M, Omedo I, et al. A review of the frequencies of Plasmodium falciparum Kelch 13 artemisinin resistance mutations in Africa. Int J Parasitol Drugs Drug Resist 2021;16:155-61. [DOI:10.1016/j.ijpddr.2021.06.001] [PMID] [PMCID]

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