Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

James Abugri; Felix Ansah; Kwaku P Asante; Comfort N Opoku; Lucas A Amenga-Etego; Gordon A Awandare

doi:10.12688/aasopenres.12825.2

Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

AAS Open Res. 2018 Dec 3:1:1. doi: 10.12688/aasopenres.12825.2. eCollection 2018.

Authors

James Abugri^{1

2

3}, Felix Ansah^{1

2}, Kwaku P Asante⁴, Comfort N Opoku⁵, Lucas A Amenga-Etego^{1

2

6}, Gordon A Awandare^{1

2}

Affiliations

¹ West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
² Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
³ Department of Applied Chemistry and Biochemistry, Faculty of Applied Sciences, University for Development Studies, Tamale, Ghana.
⁴ Kintampo Health Research Centre, Ghana Health Service, Kintampo, Ghana.
⁵ Ledzokuku Krowor Municipal Assembly Hospital, Accra, Ghana.
⁶ Navrongo Health Research Centre, Navrongo, Ghana.

Abstract

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Sulphadoxine-pyrimethamine (SP) which was the second line antimalarial drug in Ghana, was now adopted for intermittent preventive treatment of malaria in pregnancy (IPTp). Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we employed restriction fragment length polymorphism polymerase chain reaction to genotype and compare single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter ( pfcrt, PF3D7_0709000), multidrug resistance ( pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase ( pfdhfr, PF3D7_0417200) and dihydropteroate synthase ( pfdhps, PF3D7_0810800) genes. Parasites were collected from children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) in 2012-2013 and 2016-2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10.2% and 65.1% of infections, respectively. The majority of the isolates harboured the antifolate resistance-associated pfdhfr alleles 51I (83.4%), 59R (85.9 %) and 108N (90.5%). Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G , which was more common in Accra compared to Kintampo for the 2016-2017 isolates. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination ( I ₅₁ R ₅₉ N ₁₀₈/ G ₄₃₇). CQ resistance alleles decreased during the 12 years after CQ withdrawal, but an mediate SP resistance alleles increased. Conclusion: Surveillance of the prevalence of resistance alleles is necessary in monitoring the efficacy of antimalarial drugs.

Keywords: Antifolates; Chloroquine; Drug resistance; Malaria; Plasmodium falciparum.

Grants and funding

WT_/Wellcome Trust/United Kingdom