PurposeThe 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-Pfmdr1, 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 Pfcrt, Pfdhps, Pfdhfr, and PfK13 genes from 2011 to 2014 in Southeastern Gabon.MethodsA total of 233 Plasmodium falciparum 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. Pfcrt, Pfdhps, Pfdhfr, and the propeller domain of PfK13 were sequenced for all isolates.ResultsThe overall prevalence (3.7%–11.5%) of the wild-type haplotype Pfcrt 72-76 CVMNK was not significantly different between 2011 and 2014 in Southeast Gabon. For Pfdhfr (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 Pfdhps, 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 PfK13.ConclusionDespite 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.
Plasmodium falciparum malaria remains a major public health challenge in sub-Saharan Africa. Plasmodium falciparum drug resistance mediated by polymorphisms in the Pfmdr1 gene contributes to the persistence of the disease on the African continent. This study investigated P. falciparum infection features and differences in the Pfmdr1 genotypes between symptomatic and asymptomatic malaria cases in a rural area in east-central Gabon.Patients and Methods: A total of 875 children aged from 5 to 185 months were screened for P falciparum infection using Optima-IT ® rapid diagnostic tests and standard microscopy. Pfmdr1 polymorphisms at codons 86, 184 and 1246 were investigated using PCR-RFLP. Results: Among the 448 P. falciparum-infected children, 57.08% (n=250) were symptomatic and 42.92% (n=198) were asymptomatic (p < 0.0001). In a sub-set of 79 isolates, the Pfmdr1 wild-type N86 was more prevalent in symptomatic (100%) than in asymptomatic infections (70.7%) (p=0.007). The mutant 86Y and mixed 86N/Y genotypes were observed only in asymptomatic infections. The Y184 and 184F genotype prevalences (39.1% vs 19.4% and 60.9% vs 80.6%, respectively) were not significantly different between the two groups (p=0.097). The prevalence of the wild-type D1246 differed significantly between symptomatic (10.3%) and asymptomatic (100%) (p < 0.0001). The NFD and YFD haplotypes were more prevalent in asymptomatic than in symptomatic infections [(61.9% vs 31%; p=0.005) and (16.7% vs 0.0%; p=0.01)], whereas the NYD and YYD haplotypes were not significantly different between the two groups [(21.4% vs 14.3%, p=0.39) and (0.0% vs 7.1%, p=0.24)]. Conclusion: Our results confirm a high transmission of P. falciparum infection in rural Gabon, with a high prevalence of asymptomatic carriage. The higher prevalences of wildtype N86 in symptomatic infections and of D1246 in asymptomatic infections suggest a pathogenicity associated with polymorphisms in Pfmdr1. These results highlight the need to monitor the efficacy of artemisinin-based combination therapies in Gabon.
Background Malaria remains a major public health issue in the world despite a decline in the disease burden. However, though symptomatic malaria is diagnosed and treated, asymptomatic infections remain poorly known and support transmission. This study assessed the prevalence of symptomatic and asymptomatic plasmodial infections in three areas in Gabon to monitor and evaluate the impact of malaria. Methods A cross-sectional study was conducted at the Centre Interdisciplinaire de Recherches Médicales de Franceville (CIRMF). Febrile children and without fever, aged 6 months to 15 years from three localities (Franceville, Makokou, Lastoursville) in south-eastern Gabon were included in this study. The Plasmodium Spp infection was determined by microscopy and/or rapid diagnostic tests (RDT) followed by PCR according to the Snounou method. The data were recorded in Excel, and the statistical analyzes were performed using the software R version R 64x 3.5.0. Results Two thousand three hundred and eighty-one (2381) children were screened and included in this analysis. The mean age was significantly higher in asymptomatic children compared to symptomatic children. Hematological parameters varied significantly according to regions and clinical signs. The overall prevalence of Plasmodium infection was 40% (952/2381). In the urban area (Franceville) the prevalence of plasmodial infection was not significantly different between symptomatic and asymptomatic children. In contrast, a high prevalence of symptomatic plasmodial infection was found in infected children in rural and semi-rural areas. Among the three plasmodial species (Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale) identified, Plasmodium falciparum was the most widespread, and its prevalence was not significantly different between symptomatic and asymptomatic children in the three localities. In rural and semi-rural areas, a higher or lower prevalence of Plasmodium malariae was demonstrated in asymptomatic children. Conclusion This study showed that the prevalence of plasmodial infection varied according to the regions and clinical signs. The main species was Plasmodium falciparum, but in asymptomatic children the prevalence of Plasmodium malariae was high in rural areas. To help fight malaria more effectively asymptomatic infections should be taken into account and treated.
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