Prevalence of PfATPase6 Gene Mutation for ACT Resistance in Plasmodium falciparum Malaria Parasites among Patients with Fever in Osun State Health Facilities, Nigeria

Document Type : Research Article

Authors

1 Osun State Malaria Elimination Program, Osun State Ministry of Health, Nigeria

2 Department of Community Medicine, Osun State University, Osogbo, Nigeria

3 Research Laboratory, International Foundational Against Infectious Disease in Nigeria, Nigeria

Abstract

Malaria remains a significant public health challenge in Nigeria, particularly in Osun State, where Plasmodium falciparum is the predominant species responsible for the disease. This research aimed to assess the prevalence of Plasmodium falciparum ATPase 6 gene (PfATPase6) mutations associated with artemisinin-based combination therapy (ACT) resistance in P. falciparum isolates from febrile patients attending health facilities across eight local government areas (LGAs) in Osun State, Nigeria. A cross-sectional study was conducted across eight LGAs in Osun State, where between 36 and 40 febrile patients were randomly selected from each local government area. A total of 315 respondents (175 females and 140 males) participated, with a mean age of 16.7 years. Rapid diagnostic tests (RDTs) for malaria were performed, and samples from positive cases were analyzed for the presence of PfATPase6 gene mutations using polymerase chain reactions. Out of 293 valid malaria RDTs conducted, 127 (43.3%, CI 37.59%-49.23%) tested positive for P. falciparum. The mean age of patients who tested positive was 11.12 years, which was statistically significant (p < 0.05). The highest malaria prevalence rate was recorded in Orolu LGA (57.5%), while the lowest was in Osogbo LGA (29.41%). Socio-demographically, malaria prevalence was highest among respondents with no more than primary school education (59.7%). Notably, none of the 127 P. falciparum positive samples harbored the PfATPase6 gene mutation. The study reveals a substantial burden of malaria in Osun State, particularly among younger patients and those with lower educational attainment. However, the absence of PfATPase6 gene mutations in all positive samples suggests that ACTs remain effective in this region.

Keywords

Main Subjects


WHO. (2021). Word Malaria Report 2021. In Word Malaria report Geneva: World Health Organization. (2021). Licence: CC
Schantz-Dunn, J., & Nour, N. M. (2009). Malaria and pregnancy: A global health perspective. Reviews in Obstetrics and Gynecology, 2 (3), 186. https://doi.org/10.3909/riog0123
Nankabirwa, J., Brooker, S. J., Clarke, S. E., Fernando, D., Gitonga, C. W., Schellenberg, D., & Greenwood, B. (2014). Malaria in school-age children in Africa: an increasingly important challenge. Tropical Medicine and International Health, 19(11): 1294- 1309. https://doi.org/10.1111/tmi.12374
WHO. (2017). Artemisinin and artemisinin-based combination therapy resistance: status report. https://apps.who.int/iris/handle/10665/255213
Igbasi, U., Oyibo, W., Omilabu, S., Quan, H., Chen, S. B., Shen, H. M., ... & Zhou, X. N. (2019). Kelch 13 propeller gene polymorphism among Plasmodium falciparum isolates in Lagos, Nigeria: Molecular epidemiologic study. Tropical Medicine & International Health, 24(8), 1011-1017. https://doi.org/10.1111/tmi.13273
Afoakwah, R., Acheampong, D. O., Boampong, J. N., Sarpong-Baidoo, M., Nwaefuna, E. K., & Tefe, P. S. (2011). Typhoid-Malaria co-infection in Ghana. European Journal of Experimental Biology, 1(3), 7-13. Available on: https://www.primescholars.com/european-journal-of-experimental-biology.html
Nassar, A. S., Alao, M., Ekpo, O., Adeleke, M., & Muhibi, M. A. (2016). Artemisinin resistance marker of Plasmodium falciparum in Osogbo Metropolis, south-west, Nigeria. Nigerian Journal of Parasitology, 37(2), 256-259. https://doi.org/10.4314/njpar.v37i2.24
Tola, M., Ajibola, O., Idowu, E. T., Omidiji, O., Awolola, S. T., & Amambua-Ngwa, A. (2020). Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria. BMC Research Notes, 13, 1-7. https://doi.org/10.1186/s13104-020-05334-5
Chilongola, J., Ndaro, A., Tarimo, H., Shedrack, T., Barthazary, S., Kaaya, R., ... & Lusingu, J. (2015). Occurrence of Pfatpase6 single nucleotide polymorphisms associated with Artemisinin resistance among field isolates of Plasmodium falciparum in North‐Eastern Tanzania. Malaria Research and Treatment, 2015(1), 279028 https://doi.org/10.1155/2015/279028
Panda, B. B., Meher, A. S., & Hazra, R. K. (2019). Comparison between different methods of DNA isolation from dried blood spots for determination of malaria to determine specificity and cost effectiveness. Journal of Parasitic Diseases, 43(3), 337-342. https://doi.org/10.1007/s12639-019-01136-0
Dawaki, S., Al-Mekhlafi, H. M., Ithoi, I., Ibrahim, J., Atroosh, W. M., Abdulsalam, A. M., ... & Lau, Y. L. (2016). Is Nigeria winning the battle against malaria? Prevalence, risk factors and KAP assessment among Hausa communities in Kano State. Malaria Journal, 15, 1-14. https://doi.org/10.1186/s12936-016-1394-3
Aju-Ameh, C., Awolola, S., Mwansat, G., & Mafuyai, H. (2017). Prevalence of asymptomatic malaria in selected communities in Benue state, North Central Nigeria: a silent threat to the national elimination goal. Endorium Journal Epidemiol, 3, 1-8. https://doi:10.5348/E06-2017-3-OA-1
Nwaneli, E. I., Eguonu, I., Ebenebe, J. C., Osuorah, C. D. I., Ofiaeli, O. C., & Nri-Ezedi, C. A. (2020). Malaria prevalence and its sociodemographic determinants in febrile children-a hospital-based study in a developing community in South-East Nigeria. Journal of Preventive Medicine and Hygiene, 61(2), E173. https://doi.org/10.15167/2421-4248/jpmh2020.61.2.1350
Jemimah, Y., Victor, O., Elizabeth, A., Akpu, P., & Lynda, A. (2019). Plasmodium falciparum infection among febrile patients attending a tertiary healthcare facility in Central Nigeria: prevalence, hematologic and socio-demographic factors. International Journal of Tropical Disease, 2 (2), 1-6. https://doi.org/10.23937/ijtd-2017/1710019
Omale, U. I., Oka, O. U., Okeke, I. M., Azuogu, B. N., Alo, C., Madubueze, U. C., ... & Anene, O. C. (2021). Demand for malaria rapid diagnostic test, health care-seeking behaviour, and drug use among rural community members with fever or malaria-like illness in Ebonyi state, Nigeria: a cross-sectional household survey. BMC Health Services Research, 21(1), 857. https://doi.org/10.1186/s12913-021-06865-8
Nigeria Demographic and Health Surveys. 2018. Pg. 330. Nigeria Malaria indicator Survey 2015. P. 3. Available on: https://dhsprogram.com/pubs/pdf/MIS20/MIS20.pdf
Rosenthal, P. J., John, C. C., & Rabinovich, N. R. (2019). Malaria: how are we doing and how can we do better? The American Journal of Tropical Medicine and Hygiene, 100(2), 239. https://doi.org/10.4269/ajtmh.18-0997
Kimenyi, K. M., Akinyi, M. Y., Mwikali, K., Gilmore, T., Mwangi, S., Omer, E., ... & Ochola-Oyier, L. I. (2024). Distinct transcriptomic signatures define febrile malaria depending on initial infective states, asymptomatic or uninfected. BMC Infectious Diseases, 24(1), 140. https://doi.org/10.1186/s12879-024-08973-2
James, S., & Santos, M. (2023). The promise and challenge of genetic biocontrol approaches for malaria elimination. Tropical Medicine and Infectious Disease, 8(4), 201. https://doi.org/10.3390/tropicalmed8040201
Ouji, M., Augereau, J. M., Paloque, L., & Benoit-Vical, F. (2018). Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination. Parasite, 25 (24), 1-12. https://doi.org/10.1051/parasite/2018021
Ezeigbo, O. R., Agomoh, N. G., & Ezeigbo, I. C. (2016). The role of community involvement in malaria control and prevention in Abia State, Nigerian. International Journal of Tropical Disease and Health, 19(4), 1-8. https://doi.org/10.9734/IJTDH/2016/28518
Ajegena, B. K., & Oti, V. B. (2020). The challenges of using insecticide-treated nets (ITNs) in curbing malaria in Nigeria: A 2000-2018 systematic review. Journal of Infectious Diseases and Epidemiology, 6 (4), 1-8. https://doi.org/10.23937/24743658/1510140
van Der Pluijm, R. W., Tripura, R., Hoglund, R. M., Phyo, A. P., Lek, D., Ul Islam, A., ... & Valeche, N. (2020). Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. The Lancet, 395(10233), 1345-1360. https://10.1016/S0140-6736(20)30552-3