Prevalence of Molecular Markers of Plasmodium Falciparum Resistance to Proguanil and Pyrimethamine in Children with Haemoglobin Phenotypes SS and AA in Benin City, Nigeria

West Afr J Med. | 2021 Dec 30;Vol. 38(12): |1183-1189

https://doi.org/10.55891/wajm.v38i12.47

Authors

  • I G Enato Institute of Child Health, University of Benin, Benin City, Edo State, Nigeria.
  • A E Sadoh Edo State University, Uzairue, Edo State, Nigeria
  • O M Ibadin Department of Child Health, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
  • M E Odunvbun Department of Child Health, University of Benin, Benin City, Edo State, Nigeria.

Abstract

Background: Chemoprophylaxis against Plasmodium falciparum (Pf) is advocated in children with sickle cell anaemia (SCA). Among them, antifolates: proguanil and pyrimethamine had replaced initial chemoprophylactic drugs because of widespread resistance. In recent past, efficacy of these antifolates has also come under scrutiny due to increasing level of drug resistance. Specific point mutations on Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) have been linked with resistance to proguanil and pyrimethamine and they can be used as markers in monitoring prevalence and level of resistance to the drugs.

Objectives: To determine the prevalence of molecular markers of Plasmodium falciparum resistance to proguanil and pyrimethamine in children with SCA.

Methods: A total of 146 Plasmodium falciparum isolates (71 from children with SCA and 75 from those with Haemoglobin AA: HbAA) were evaluated for point mutations and mutant haplotypes on the pfdhfr gene using nested polymerase chain reaction amplification followed by direct sequencing.

Results: The triple (S108N+N51I+C59N) mutant haplotype was present in 100.0% and 96.0% of samples from children with SCA and HbAA respectively. S108T, A16V and 1164L mutationswere not present in both groups.

Conclusion: High prevalence of triple mutant haplotype mediates significant resistance to pyrimethamine and implies that pyrimethamine resistance is fixed in the study locale. However, the absence of pfdhfr S108T and A16V mutations, which indicate specific resistance to proguanil but not to pyrimethamine, suggests that proguanil is still useful even in the face of pyrimethamine resistance. The threat of proguanil resistance is however real due to high prevalence of the triple mutant pfdhfr haplotype.

Keywords: Drug-resistance; Molecular markers; Plasmodium falciparum; Proguanil; Pyrimethamine.

Published

2021-12-30

Issue

Vol. 38 No. 12 (2021): The West African Journal of Medicine

Section

Articles
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