EXPRESSION OF SULPHADOXINE-PYRIMETHAMINE (SP) RESISTANCE MARKERS IN Plasmodium falciparum AMONG PREGNANT WOMEN IN OYO STATE: A POTENTIAL THREAT TO MALARIA PREVENTION IN PREGNANCY

Volume 9, Issue 2, April 2024     |     PP. 34-49      |     PDF (457 K)    |     Pub. Date: April 1, 2024
DOI: 10.54647/cm321077    25 Downloads     20825 Views  

Author(s)

Mufutau Mosunmade AZEEZ, Department of Medical Laboratory Science, Faculty of Basic Medical and Health Sciences, Lead City University, Ibadan, Nigeria
Frederick Olusegun AKINBO, Department of Medical Laboratory Science, School of Basic Medical Sciences, College of Medical Sciences, University of Benin, Benin City, Nigeria

Abstract
Background: The interrelationship between pregnancy, Plasmodium falciparum infection and antimalarial drug resistance serve as recipe for adverse outcomes that impact on the mother and the foetus, hence the adoption of intermittent preventive treatment in pregnancy (IPTP) using sulphadoxine-pyrimethamine (SP). Antifolate drugs have been in wide use in Nigeria and other African countries where high level resistance (through dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) gene mutations) to the drugs has been observed. This study was conducted to determine the expression of genetic markers of resistance to SP in Plasmodium falciparum infection among pregnant women in Oyo State.
Materials and Methods: Eighty-two (82) dry blood spots of malaria positive samples on Whatman no 1 filter paper were used for parasite DNA extraction and subsequent detection of SP-resistance genetic markers using restriction fragment length polymorphism (RFLP) with specific restriction enzymes for Pfdhfr and Pfdhps mutant genes.
Results: The expression of Plasmodium falciparum dihydrofolate reductase (Pfdhfr) mutant gene was 92.68% at codon 51 and 59 respectively. Similarly, Pfdhps mutant gene was expressed in 95.12% of P. falciparum studied at codons 437G and 540E of the parasite studied.
Conclusion: The high prevalence of these 2 major markers of SP-resistance in this study, portends a serious threat to the continued usage of SP in the intermittent preventive treatment in pregnancy (IPTP) especially in the study area. It is therefore imperative to intensify efforts at finding more effective alternatives while also ensuring testing before drug use and avoiding self-medication.

Keywords
sulphadoxine-pyrimethamine, resistance markers, Pfdhfr, Pfdhps, Plasmodium falciparum

Cite this paper
Mufutau Mosunmade AZEEZ, Frederick Olusegun AKINBO, EXPRESSION OF SULPHADOXINE-PYRIMETHAMINE (SP) RESISTANCE MARKERS IN Plasmodium falciparum AMONG PREGNANT WOMEN IN OYO STATE: A POTENTIAL THREAT TO MALARIA PREVENTION IN PREGNANCY , SCIREA Journal of Clinical Medicine. Volume 9, Issue 2, April 2024 | PP. 34-49. 10.54647/cm321077

References

[ 1 ] WHO. World malaria report. Geneva, World Health Organization; 2018
[ 2 ] Federal Ministry of Health (FMOH) (2014). National Guidelines for Diagnosis and Treatment of Malaria. Federal Ministry of Health, Abuja. Nigeria.
[ 3 ] Monif, G.R.G. and Baker, D.A. eds. (2004).Infectious Disease in Obstetrics and Gynaecology. 6th ed. New York: Parthenon: 2004:280-286
[ 4 ] World Health Organization (2016). World Malaria Report, 2016. http://www.who.int/malaria/publications/world-malaria-report-20156/en/ accessed 28 Dec, 2016.
[ 5 ] Myles, D., Traser, M. and Cooper, A. (2003). Change and adaptation in pregnancy: Immunity. Textbook of midwives, (14th edn), 197, Churchill Livingstone, UK.
[ 6 ] Schantz-Dunn, J. and Nour, N.M. (2009). Malaria and Pregnancy: A Global Health Perspective. Rev Obstet Gynaecol. 2(3):186-192. doi:10.3909/riog0091
[ 7 ] Frank, M.D., Robinson-Bassey, G.C. Akaeze, G.O. (2016). Prevalence of Malaria Parasitaemia among Pregnant Women Attending Three Selected Health Centres in Ideato South Local Government Area, Imo State. Obs Gynaecol Intern J. 4(3): 1-5
[ 8 ] Agomo, C.O., Oyibo, W.A., Sutherland, C., Hallet, R. and Oguike, M. (2016). Assessment of Markers of Antimalarial Drug Resistance in Plasmodium falciparum Isolates from Pregnant Women in Lagos, Nigeria. PLoS One.Jan 25; 11 (1):e0146908. doi:10.1371/journal.pone.0146908. PMID:26808627; PMCID: PMC4726598
[ 9 ] Azeez, M.M., and Akinbo, F.O. (2022). “Asymptomatic” Plasmodium falciparum parasitaemia and micronutrients deficiencies among pregnant women in Oyo state. Biomed BiotechnolRes J; 6:185-92
[ 10 ] Jiang, T., Chen, J., Fu, H., Wu, K., Yao, Y., Eyi, JUM., Matesa, RA., Obono, MMO., Du, W., Tan, H., Lin, M., Li, J. (2019). High prevalence of Pfdhfr-Pfdhps quadruple mutations associated with sulphadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from Bioko island, Equatorial Guinea. Malar J 26; 18(1): 101.doi:10.1186/s12936-019-2734-x. PMID: 30914041; PMCID: PMC6434785.
[ 11 ] Nigeria Population Commission (NPC). Census Arranged by State 2006.
[ 12 ] Berzosa P, de Lucio A, Romay-Barja M, Herrador Z, Gonzalez V, Garcia L, et al. (2018). Comparison of three diagnostic methods (microscopy, RDT and PCR) for the detection of mlaria parasites in representative samples from Equatorial Guinea. Malar J. 17; 333
[ 13 ] Kishoyian, G., Njagi, E.N.M., Orinda, G.O., Kimali, F.T., Thiongo, F.T. and Malake-Muhia, D. (2019). Molecular Monitoring of Plasmodium falciparum Resistance to Sulfadoxine-pyrimethamine in Western Kenya, 14 years after its withdrawal. Annals Medical Health Science Research. 9:633-639.
[ 14 ] Falade, C.O., Salako, L.A., Sowunmi, A., Oduola, A.M. and Larcier, P. (1997). Comparative efficacy of halofantrine, chloroquine and sulfadoxine-pyrimethamine for the treatment of acute uncomplicated falciparum malaria in Nigerian children. Transitional R Social Tropical and Medical Hygiene. 91:58 – 62
[ 15 ] Bates, S.J., Winstanley, P.A., Watkins, W.M., Alloueche, A. and Bwika, J., Happi, C., Kremsner, P.G., KublinJ.G., Premji, Z. and Zibley, C.H. (2004). Rare, highly pyrimethamine-resistant alleles of the Plasmodium falciparum dihydrofolate reductase gene from 5 African sites. Journal of Infectious Disease. 190:1783–1792
[ 16 ] Happi, C.T., Gbotosho, G.O., Folarin, O.A., Akinboye, D.O., Yusuf, B.O., Ebong, O.O., Sowunmi, A., Kyle, D.E., Milhous,W., Wirth, D.F.and Oduola, A.M. (2005). Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Tropical. 95(3):183 – 193.
[ 17 ] Ojurongbe O, Oyedeji S I, Oyibo W A, Fagbenro-Beyioku A F, Kun J F. Molecular surveillance of drug-resistant Plasmodium falciparum in two distinct geographical areas in Nigeria,Wien Klin Wochenschr.. Middle Euro J Med. 2010; 122:681-685
[ 18 ] Asua V, Vinden J, Conrad M D, Lugac J, Kigosi S P, Kamya M R, et al. Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda. Antimicrob Agents Chemother 2019; 63:e01818-18.
[ 19 ] Quan, H., Igbasi, U., Oyibo, W., Omilabu, S., Chen, S., Chen, H., Okolie, C., Chen, J. and Zhou, X. (2020). High multiple mutations of Plasmodium falciparum-resistant genotypes to sulphadoxine-pyrimethamine in Lagos, Nigeria. Infectious Diseases of Poverty. 9:91-102.
[ 20 ] Bazie, V.B., Ouattara, A.K., Sagna, T., Compaore, T.R., Soubeiga, S.T., Sorgho, P.A., Yonli, A.T. and Simpore, J. (2020). Resistance of Plasmodium falciparum to Sulfadoxine-Pyrimethamine (Dhfr and Dhps) and Artemisinin and Its Derivatives (K13): A Major Challenge for Malaria Elimination in West Africa. Journal of Biosciences and Medicines. 8: 82-95.
[ 21 ] Gregson, A. and Plowe, C.V. (2005). Mechanisms of resistance of malaria parasites to Antifolates. Pharmacology Review 57:117 – 145. https://doi.org/10.1124/pr.57.1.4.
[ 22 ] Desai, M., Hill, J., Fernandes, S., Walker, P., Pell, C., Gutman,J., Kayen, K., Gonzalez, R., Webster, J., Greenwood, B., Cot, M. and Ter Kuile, F.O. (2018). Prevention of malaria in pregnancy. The Lancet Infectious Disease. 18:e119-32
[ 23 ] Cisse, B., Ba, E.H., Sokhna, C., NDiaye, J.L., Gomis, J.F., Dial, Y., Pitt, C., NDiaye, M.C., Faye, E., NDiaye, M., LO, A., Tine, R., Faye, S., Faye, B., Sy, O., konate, L., Kouevijdin, E., Flach, C., Faye, O., Trape, J., Sutherland, C., Fall, F.B., Thior, P.M., Faye, O.K., Greenwood, B. and Milligan, P. (2016). Effectiveness of Seasonal Malaria Chemoprevention in children under ten years of age in Senegal: A Stepped-Wedge Cluster-Randomised Trial. PLoS Medicine. 13(11):e1002175.
[ 24 ] Fagbemi, K.A., Adebusuyi, S.A., Nderu, D., Adedokun, S.A., Pallerla, S.R., Amoo, A.O.J., Thomas, B.N., Velavan, T.P., Ojurongbe, O. (2020). Analysis ofsulphadoxine-pyrimethamine resistance-associated mutationsPlasmodium falciparum isolates obtained from asymptomatic pregnant women in Ogun State, Southwest Nigeria. Infect Genet Evol. 85:104503. doi: 10.1016/j.meegid.2020.104503. Epub 2020 Aug 15. PMID: 32805431