Genetic architecture of plasmodium falciparum and impacts on Prophylaxies in Rwanda and Cameroon

Abstract

Malaria remains a major public health challenge in sub-Saharan Africa. Increasing resistance to antimalarial drugs such as Malarone (atovaquone–proguanil) and Lariam (mefloquine) threatens the effectiveness of chemoprophylaxis, particularly in mobile populations. This study aimed to assess molecular markers associated with resistance to proguanil, atovaquone, and mefloquine by analyzing mutations in the dhfr, cytb, and pfmdr1 genes of Plasmodium falciparum isolates from Rwanda and Cameroon. A total of 339 samples were included in this study. Among them, 170 isolates from Rwanda were analyzed for mutations in the dhfr, cytb, and pfmdr1 genes, while 169 isolates from Cameroon were analyzed exclusively for cytb mutations. Targeted PCR amplification and Sanger sequencing combined to Oxford Nanopore Technology were used to detect key point mutations: N51I, C59R, S108N, and I164L in dhfr; Y268S in cytb; and Y184F in pfmdr1. In Rwanda, dhfr mutations were highly prevalent: N51I (97.1%), C59R (94.7%), S108N (98.2%), and I164L (30.6%). Cameroonian samples showed a similar triple mutant profile based on previous data, though I164L was not detected. No Y268S mutation was found in cytb from either country, indicating continued atovaquone efficacy. The Y184F mutation in pfmdr1 was observed in 48.8% of Rwandan isolates, while recent studies indicate a prevalence of approximately 60% in Cameroon. These findings suggest that proguanil resistance is near fixation, while atovaquone remains effective but at risk. The growing presence of pfmdr1 mutations raises concerns about declining mefloquine efficacy. The study highlights the urgent need for region-specific prophylaxis policies and continuous molecular surveillance