Allelic frequencies of mutants of the Plasmodium falciparum, quinoline and folate metabolizing genes in the west region of Cameroon

Abstract

The emergence and spread of Plasmodium falciparum (P.f) drug resistance is still a major concern in Sub-Saharan Africa and warrants that its evolution be monitored continuously. The present study aimed at determining the distribution of key P.f drug resistance-mediating alleles in circulating malaria parasites in the West region of Cameroon. A cross sectional hospital-based study was conducted in Dschang and Ngounso in the West region of Cameroon. The Pfcrt, Pfmdr1, and the Pfdhps genes were amplified through nested PCR in 208 malaria-infected samples of the 301 febrile outpatients enrolled. The presence or absence of mutations in the K76T, N86Y, A437G and A581G codons of these P.f. genes respectively were determined through restriction digestion analysis. The proportion of different alleles were estimated as percentages and compared between two study sites using the Chi square test. A p value <0.05 was considered significant. A high prevalence (75.6%) of the 437G allele was observed. It was significantly different between Dschang and Ngounso (62% vs. 89.2%, X² = 19.6, P = 0.00005). Equally observed was a 19.2% (95%CI: 13.3-25.6) of the dhps-581G mutant allele. Furthermore, we observed the Pfcrt-76T, Pfmdr1-N86 mutations in 73.0% (67.5-79.7) and 87.2% (83.2-91.9), and 3.0% (0.0-9.6) and 12.8% was observed for the Pfcrt-K76T and Pfmdr1-N86Y respectively. When biallelic haplotypes were constructed from alleles of the three genes, same pattern was seen. Overall, 73% and 87% of circulating P. falciparum isolates carried wild type alleles at Pfmdr1-N86Y and Pfcrt-K76T. On the other hand, we found more parasites with mutant alleles at dhps (437G and 581G) loci which may reflect possible drug-related selection of this mutant in the parasite population. Continuous monitoring of these mutations is recommended to pre-empt a loss in sulphadoxine-pyrimethamine efficacy in malaria chemoprevention programs.

Keywords: Cameroon; Drug resistance; Malaria; Ngounso; Pfcrt; Pfdhps; Pfmdr1; West region.

Figure 1

Frequency of aminoquinoline Upper panel (A: Pfcrt 76 and B: Pfmdr1 86) and antifolate Lower Panel (C: pfdhps 437 and D: pfdhps 581) mutations within the study population of Dschang and Ngounso.

Figure 2

Biallelic haplotypes of Pfcrt-K76T and Pfmdr1-N86Y markers of resistance in the study sites.