Investigating Pfk13 mutations in Plasmodium falciparum natural populations from two malaria-endemic areas of Cameroon

Abstract

Background: The emergence of Plasmodium falciparum resistance to artemisinin is a huge concern in Africa. We investigated and characterized mutations of Pfk13 propeller sequences from P. falciparum isolates across two endemic areas with different eco-geographical settings in Cameroon.

Methods: A total of 259 dried blood spot samples were collected through a cross-sectional survey in two health facilities located in Bimengue (rural area) and the Efoulan District Hospital in Yaoundé (urban area). The molecular analysis of Pfk13 was performed using nested polymerase chain reaction followed by Sanger sequencing.

Results: Our findings highlight that of the 23 mutations found, most of the genetic variants were observed in Yaoundé, suggesting a possible higher drug pressure in this locality. Three Pfk13 mutations (F446S, C469W and A681D) were found in polymorphic sites known to be associated with artemisinin resistance, but with different amino acid substitutions. In addition, three other mutations have already been reported to circulate in other African countries, with an unknown impact on delayed response to artemisinin therapy (P475L, S477F and F628L).

Conclusions: Although there is an absence of validated artemisinin resistance-associated polymorphisms in the study, the results highlight the need for further studies to quantify the frequency of these and other Pfk13 gene polymorphisms over time.

Keywords: Pfk13 gene; Plasmodium falciparum malaria; Cameroon; artemisinin resistance; urban and rural malaria.