Prevalence and Implications of Plasmodium Falciparum Multidrug Resistance Gene Mutations (pfmdr1) Among Pediatric Patients with Malaria in Kano, Nigeria
Keywords:
Malaria, Resistance, Genes, Multidrug, Mutation, PatientAbstract
A genetic indicator of the parasites' vulnerability to anti-malarial medications is the Plasmodium falciparum multidrug resistance gene 1 (pfmdr1). In this study, malaria patients aged 0–14 who were treated at Murtala Muhammad Specialist Hospital in Kano, Nigeria, were evaluated for multidrug-resistant resistance gene 1 (MDR1) mutations. After confirming the malaria parasite density in 100 children's samples, the samples were genotyped using BigDye (v3.1) terminator cycle sequencing to look for two SNPs in pfmdr1 on samples with high and moderate parasite densities. Fisher's exact (FE) tests and Pearson Chi-square were used to evaluate the data. Of the 100 samples, 57% of the patients had low (+) malaria parasite densities, 28% had moderate (++) densities, and 15% had high (+++) densities. Only seven samples were successfully amplified for the pfmdr1 gene located at codon 1246, whereas 31 were successfully amplified and processed for the pfmdr1 gene located at codon 86 with an amplicon size of 534 bp. A pfmdr1-N86Y mutation was found in one sample (3.2%). Additionally, the results indicated no correlation (P = 0.4237) between sex and the pfmdr1 SNP mutation. Nonetheless, there was a significant correlation (P = 0.0043) between the pfmdr1 mutation and the age groups. According to the current study, Kano state in northern Nigeria may have strains of P. falciparum that are less sensitive to the artemisinin component of artemisinin-based combination therapy (ACT). The Plasmodium falciparum parasites' development of this resistance gene puts malaria chemotherapy at serious risk because the parasite will be immune to the widely prescribed anti-malarial medications.
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Abubakar, U. F., Adam, R., Mukhtar, M. M., Muhammad, A., Yahuza, A. A., & Ibrahim, S. S. (2020). Identification of mutations in antimalarial resistance gene Kelch13 from Plasmodium falciparum isolates in Kano, Nigeria. Tropical Medicine and Infectious Disease, 5(2), 85. https://doi.org/10.3390/tropicalmed5020085
Achan, J., Talisuna, A., & Erhart, A. (2011). Quinine, an old anti-malarial drug in a modern world: Role in the treatment of malaria. Malaria Journal, 10, 144. https://doi.org/10.1186/1475-2875-10-144
Achieng, A. O., Muiruri, P., Ingasia, L. A., Opot, B. H., Juma, D. W., & Yeda, R. (2015). 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. International Journal for Parasitology: Drugs and Drug Resistance, 5, 92–99. https://doi.org/10.1016/j.ijpddr.2015.05.005
Adamu, A., Jada, M. S., Haruna, H. M. S., Yakubu, B. O., Ibrahim, M. A., Balogun, E. O., Sakura, T., Inaoka, D. K., Kita, K., Hirayama, K., Culleton, R., & Shuaibu, M. N. (2020). Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: Implications for the continued use of artemether-lumefantrine in the region. Malaria Journal, 19(1), 439. https://doi.org/10.1186/s12936-020-03506-z
Agrawal, S., Moser, K. A., Morton, L., Cummings, M. P., Parihar, A., Dwivedi, A., Shetty, A. C., Drabek, E. F., Jacob, C. G., & Henrich, P. P. (2017). Association of a novel mutation in the Plasmodium falciparum chloroquine resistance transporter with decreased piperaquine sensitivity. Journal of Infectious Diseases, 216, 468–476. https://doi.org/10.1093/infdis/jix334
Al-Koofee, A. F., & Mubarak, M. H. S. (2020). Genetic polymorphisms. In M. Çalışkan, O. Erol, & G. C. Öz (Eds.), Recent topics in genetic polymorphisms (pp. 1–18). IntechOpen. https://doi.org/10.5772/intechopen.88063
Amaratunga, C., Lim, P., Suon, S., Sreng, S., Mao, S., Sopha, C., Sam, B., Dek, D., Try, V., & Amato, R. (2016). Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: A multisite prospective cohort study. Lancet Infectious Diseases, 16, 357. https://doi.org/10.1016/S1473-3099(15)00487-9
Amato, D. R., Lim, P., Miotto, O., Amaratunga, C., Dek, D., Pearson, R. D., Almagro-Garcia, J., Neal, A. T., Sreng, S., & Suon, S. (2017). Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: A genotype-phenotype association study. Lancet Infectious Diseases, 17, 164–173. https://doi.org/10.1016/S1473-3099(16)30409-1
Antinori, S., Galimberti, L., Milazzo, L., & Corbellino, M. (2012). Biology of human malaria plasmodia including Plasmodium knowlesi. Mediterranean Journal of Hematology and Infectious Diseases, 4, e2012013. https://doi.org/10.4084/mjhid.2012.013
Apinjoh, T. O., Mugri, R. N., Miotto, O., Chi, H. F., Tata, R. B., Anchang-Kimbi, J. K., Fon, E. M., Tangoh, D. A., Nyingchu, R. V., & Jacob, C. (2017). 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, 6, 136. https://doi.org/10.1186/s40249-017-0350-y
Ariey, F., Randrianarivelojosia, M., & Duchemin, J. B. (2002). Mapping of a Plasmodium falciparum pfcrt K76T mutation: A useful strategy for controlling chloroquine resistance in Madagascar. Journal of Infectious Diseases, 185, 710–712. https://doi.org/10.1086/339000
Ariey, F., Witkowski, B., Amaratunga, C., Beghain, J., Langlois, A.-C., Khim, N., Kim, S., Duru, V., Bouchier, C., & Ma, L. (2014). A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature, 505, 50–55. https://doi.org/10.1038/nature12876
Ashley, E. A., Pyae Phyo, A., & Woodrow, C. J. (2018). Malaria. Lancet, 391, 1608–1621. https://doi.org/10.1016/S0140-6736(18)30324-6
Auparakkitanon, S., Chapoomram, S., Kuaha, K., Chirachariyavej, T., & Wilairat, P. (2006). Targeting of hematin by the anti-malarial pyronaridine. Antimicrobial Agents and Chemotherapy, 50(6), 2197–2200. https://doi.org/10.1128/AAC.00119-06
Barker, R. H., Courval, J. M., Banchongaksorn, T., Wirth, D. F., Rimwungtragoon, K., & Suwonkerd, W. (1992). A simple method to detect Plasmodium falciparum directly from blood samples using the polymerase chain reaction. American Journal of Tropical Medicine and Hygiene, 46(4), 416–426. https://doi.org/10.4269/ajtmh.1992.46.416
Bello, A. S., Abdullahi, N., Abdullahi, H., & Imam, A. A. (2019). Molecular markers of resistance among malaria paediatric patients attending public health hospital in Kano State-Nigeria. Malaysian Journal of Biochemistry and Molecular Biology, 3, 22–26.
Berzosa, P., Esteban-Cantos, A., García, L., González, V., Navarro, M., & Fernández, T. (2017). Profile of molecular mutations in pfdhfr, pfdhps, pfmdr1, and pfcrt genes of Plasmodium falciparum related to resistance to different anti-malarial drugs in the Bata District (Equatorial Guinea). Malaria Journal, 16, 1–10. https://doi.org/10.1186/s12936-016-1672-0
Das, S., Tripathy, S., Chattopadhayay, S., Das, B., Kar Mahapatra, S., Hati, A. K., et al. (2017). Progressive increase in point mutations associates chloroquine resistance: Even after withdrawal of chloroquine use in India. International Journal for Parasitology: Drugs and Drug Resistance, 7, 251–261. https://doi.org/10.1016/j.ijpddr.2017.06.002
Duah, N. O., Matrevi, S. A., De Souza, D. K., Binnah, D. D., Tamakloe, M. M., Opoku, V. S., et al. (2013). 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. Malaria Journal, 12, 377. https://doi.org/10.1186/1475-2875-12-377
Moyeh, M. N., Njimoh, D. L., Evehe, M. S., Ali, I. M., Nji, A. M., Nkafu, D. N., et al. (2018). 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. Malaria Research and Treatment, 2018, 7071383. https://doi.org/10.1155/2018/7071383
Okell, L. C., Reiter, L. M., Ebbe, L. S., Baraka, V., Bisanzio, D., Watson, O. J., et al. (2018). Emerging implications of policies on malaria treatment: Genetic changes in the Pfmdr1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa. BMJ Global Health, 3, e000999. https://doi.org/10.1136/bmjgh-2018-000999
Oladipo, O. O., Wellington, O. A., & Sutherland, C. J. (2015). Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated malaria in Lagos, Nigeria, four years after change of chloroquine as first-line anti-malarial medicine. Diagnostic Pathology, 10, 41. https://doi.org/10.1186/s13000-015-0276-2
Sisowath, C., Strömberg, J., Mårtensson, A., Msellem, M., Obondo, C., Björkman, A., & Gil, J. P. (2005). In vivo selection of Plasmodium falciparum pfmdr1 86 N coding alleles by artemether-lumefantrine (Coartem). Journal of Infectious Diseases, 191, 1014–1017. https://doi.org/10.1086/427997
Mustapha, U., Shehu, A., Ayuba, A. S., Gomma, H., Garba, S. N., Usman, U. S., Alasan, B. B., Garba, F. B., Harun, A. J., Yunusa, A., Magaji, S., & Dauda, S. A. (2023). Prevalence of multidrug resistance malaria among patients aged 0–14 years attending Murtala Muhammad Specialist Hospital Kano State, Nigeria. International Journal of Biological and Pharmaceutical Sciences Archive, 6(2), 37–46. https://doi.org/10.53771/ijbpsa.2023.6.2.0089
Veiga, M. I., Dhingra, S. K., Henrich, P. P., Straimer, J., Gnädig, N., Uhlemann, A. C., et al. (2016). Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. Nature Communications, 7, 11553. https://doi.org/10.1038/ncomms11553
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Copyright (c) 2024 Ummukulsum Mustapha, Ado Shehu, Yunusa Ahmad, Usman Usman Sanusi, Yusuf Misau Abdu, Attahir Ayuba Sa’ad, Aliyu Maigoro Muhammad, Abdullahi Ibrahim Haruna, Haddad Muhammad Mahfuz, Fatima Yakubu Zubairu
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