Prevalence of antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014.

Purpose: The introduction of artemisinin-based combination therapies (ACTs) in treating uncomplicated malaria and sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy drastically decreased the burden of malarial disease around the world. However, ACTs are known to select for drug resistance markers. In Gabon, artemether-lumefantrine induced an increase in the prevalence of N86-, which is associated with treatment failure. However, little data are available regarding resistance markers in Southeastern Gabon. This study aimed to evaluate the evolution of resistance haplotypes in the , , , and genes from 2011 to 2014 in Southeastern Gabon.

Methods: A total of 233 DNA samples were collected from febrile pediatric patients in South Gabon: Franceville, an urban area; Koulamoutou, a semi-urban area; and Lastourville, a rural area. , , , and the propeller domain of were sequenced for all isolates.

Results: The overall prevalence (3.7%-11.5%) of the wild-type haplotype 72-76 CVMNK was not significantly different between 2011 and 2014 in Southeast Gabon. For (codons 51, 59, 108, 164), the IRNI triple-mutant haplotype was the most prevalent (>89.0%). The ICNI and NCNI mutant haplotypes and the NCSI wild-type haplotype showed a minor prevalence. There were no differences in the distributions of these haplotypes across the 4 years and the three study sites. For , the AAKAA and SGKAA mutant haplotypes and the SAKAA wild-type haplotype were similarly present in the three areas during the study period. The AGKAA double mutant was first observed in 2013 in Franceville and in 2014 in Koulamoutou and Lastourville. Interestingly, only the A578S mutation (0.4%) and two new A494V (0.4%) and V504A (0.9%) mutations were found in .

Conclusion: Despite the withdrawal of chloroquine, the frequency of the resistant allele 76T remained high in the south of Gabon. Moreover, a high level of resistant haplotypes against IPTp-SP was found.