Malaria in urban, semi-urban and rural areas of southern of Gabon: comparison of the Pfmdr 1 and Pfcrt genotypes from symptomatic children

Abstract

BackgroundArtesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are first- and second-line treatments for uncomplicated Plasmodium falciparum malaria in Gabon. AL remains highly efficacious, but its widespread use has led to molecular selection of the NFD haplotype on Pfmdr1 and K76 in Pfcrt. In this study, plasmodial infection characteristics and the distribution of the Pfmdr1 and Pfcrt genotypes involved in reduced efficacy of artemisinin-based combination therapy (ACT) were investigated in four Gabonese localities.MethodsA cross-sectional study was conducted in the paediatric units of rural (Lastourville and Fougamou), semi-urban (Koula-Moutou) and urban (Franceville) areas. Malaria was diagnosed with the rapid diagnostic test Optimal-IT® and confirmed by blood smear. Pfmdr1 codons 86, 184 and 1246 and Pfcrt codon 76 were genotyped by PCR–RFLP and sequencing.ResultsAmong 1129 included children, the prevalence of plasmodial infection was 79.5 % at Lastourville, 53.6 % at Fougamou, 36.1 % at Koula-Moutou, and 21.2 % at Franceville. The prevalence was significantly higher among children over 60 months of age in both semi-urban (p = 0.01) and urban (p = 0.004) areas. The prevalence of Pfmdr1 wild-type N86 differed significantly between Lastourville (57.8 %) and Koula-Moutou (45.4 %) (p = 0.039). No difference in 184F-carrying parasites was found between Lastourville (73.8 %), Fougamou (81.6 %), Koula-Moutou (83.2 %), and Franceville (80.6 %) (p = 0.240). The prevalence of wild-type D1246 was significantly different between Lastourville (94.1 %), Koula-Moutou (85.6 %) and Franceville (87.3 %) (p = 0.01). The frequency of wild-type K76 was not significantly different across the four sites: Lastourville (16.5 %), Fougamou (27.8 %), Koula-Moutou (17.4 %), and Franceville (29.4 %) (p = 0.09). The mixed genotypes were only found in Lastourville and Franceville. The NFD, YFD and NYD haplotypes were mainly Lastourville (46.6, 25.8, 14.0 %), Fougamou (45.5, 9.1, 42.4 %), Koula-Moutou (35, 6.7, 40.4 %), and Franceville (40.0, 16.0, 32.0 %).ConclusionThis study shows an increase in the prevalence of childhood plasmodial infection in Gabon according to the low socio-economic level, and a high frequency of markers associated with AL treatment failure. Close monitoring of ACT use is needed.

Prevalence of <em>Plasmodium falciparum</em> antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014

“…So, some explanations of the non-significant variation of T76 prevalence between 2011 and 2014 could be the short time and also the smallness of the study effectives here. Furthermore, the T76 prevalence found at 2014 was similar to the previous findings 37. The high frequency of the resistant allele 76T in the south of Gabon may also be due to cross resistance with amodiaquine used in combination with artesunate despite the withdrawal of chloroquine 49–51…”

“…There can be a long delay in the selection of the T76 Pfcrt genotype, as shown in previous data from Zanzibar, where this selection was not observed in 2005 but clearly appeared in 2009 4,48. Indeed, recent data from Franceville showed a significant decrease of T76 prevalence around 10 years after chloroquine withdrawal 37. These findings suggest that the selection of T76 Pfcrt takes more time after changes in the antimalarial policy.…”

“…Indeed, the decrease in the malaria burden has led to a decrease in the number of infective bites, which consequently limits immune stimulation. It was previously shown that the malaria prevalence was higher in Lastourville than in Franceville and Koulamoutou, leading to a higher antimalarial immunity in Lastourville than in Franceville and Koulamoutou 37. Indeed, parasitemia was higher in the rural site in 2013 and 2014.…”

IgG antibody response against Plasmodium falciparum aminopeptidase 1 antigen in Gabonese children living in Makokou and Franceville

“…Thus, the difference in malaria prevalence between the two areas could be due, on one hand, to better management of children aged under 5 years by the anti‐malarial programs in Gabon and on the other hand to poor access to malaria control measures in semi‐urban areas. This difference in malaria prevalence could also be explained by socio‐economic level and heterogeneity of transmission in Gabon, which have been demonstrated in other endemic areas . Similarly, in this study anemia remained significantly higher in infected children living in the semi‐urban area (Makokou).…”

Circulating Cytokine Profiles of Polyparasitized Individuals in Gabon.

“…In Gabon, malaria and intestinal parasite infections (IPIs) as well as lariasis are frequently diagnosed in the population, with the prevalence varying from 1% to 75% [1,2]. This geographical co-distribution can lead to polyparasitism with possible interactions between parasite species.…”