Increased Prevalence of Mutant Allele Pfdhps 437G and Pfdhfr Triple Mutation in Plasmodium falciparum Isolates from a Rural Area of Gabon, Three Years after the Change of Malaria Treatment Policy

In Gabon, sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment during pregnancy (IPTp-SP) and for uncomplicated malaria treatment through ACTs drug. P. falciparum strains resistant to SP are frequent in areas where this drug is highly used and is associated with the occurrence of mutations on Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes. The aim of the study was to compare the proportion of mutations on Pfdhfr and Pfdhps genes in isolates collected at Oyem in northern Gabon, in 2005 at the time of IPTp-SP introduction and three years later. Point mutations were analyzed by nested PCR-RFLP method. Among 91 isolates, more than 90% carried Pfdhfr 108N and Pfdhfr 59R alleles. Frequencies of Pfdhfr 51I (98%) and Pfdhps 437G (67.7%) mutant alleles were higher in 2008. Mutations at codons 164, 540, and 581 were not detected. The proportion of the triple Pfdhfr mutation and quadruple mutation including A437G was high: 91.9% in 2008 and 64.8% in 2008, respectively. The present study highlights an elevated frequency of Pfdhfr and Pfdhps mutant alleles, although quintuple mutations were not found in north Gabon. These data suggest the need of a continuous monitoring of SP resistance in Gabon

African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker

Background: Today, the development of new and well-tolerated anti-malarial drugs is strongly justifed by the emer‑ gence of Plasmodium falciparum resistance. In 2014–2015, a phase 2b clinical study was conducted to evaluate the efcacy of a single oral dose of Artefenomel (OZ439)–piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria. Methods: Blood samples collected before treatment ofered the opportunity to investigate the proportion of mul‑ tidrug resistant parasite genotypes, including P. falciparum kelch13 mutations and copy number variation of both P. falciparum plasmepsin 2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes. Results: Validated kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated with piperaquine (PPQ) resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (>30%). Conclusions: These fndings were considered to sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to investigate in vitro susceptibility profles to PPQ of African isolates with multiple copies of the Pfpm2 gene and estimate the risk of development of PPQ resistance in Africa

Prevalence and associated factors of intestinal parasite infection by HIV infection status among asymptomatic adults in rural Gabon

Introduction: Intestinal parasites infections are endemic in Gabon. Nevertheless, they are rarely described in people living with HIV (PLHIV). Objective: The frequency of intestinal parasite infection was estimated and compared between HIV-positive and HIV uninfected individuals in Gabon; factors associated with intestinal parasites were also analysed. Material and Methods: Using a cross-sectional study design sociodemographic data, life style habits, antiretroviral therapy, cotrimoxazole use and CD4 cell count were recorded.. Stool samples from participants living in Koulamoutou and Oyem were analysed using microscopy. Chi-squared or fisher\u2019s exact tests and logistic regression were performed. Results: Among participants (n=332), female gender was predominant (73.7%; n=135/183) and the median age was 45 [33-57] years old. Among 183 samples, 53.6% (n = 98/183) were infected by intestinal parasites. The proportion was higher (72.1%) in HIV negative participants compared to PLHIV (42.6%) (p <0.01). PLHIV were more frequently poly-infected. Infection was frequent in patients using external toilets and tap water (>70.0%). Conclusion: Prevalence of intestinal parasites is higher in seronegative participants but polyparasitism is more frequent in PLHIV. Strategies are focused on HIV negative population, but this study shows the importance of sensitization for PLHIV to improve their quality of life

African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker

Background: Today, the development of new and well-tolerated anti-malarial drugs is strongly justifed by the emer‑ gence of Plasmodium falciparum resistance. In 2014–2015, a phase 2b clinical study was conducted to evaluate the efcacy of a single oral dose of Artefenomel (OZ439)–piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria. Methods: Blood samples collected before treatment ofered the opportunity to investigate the proportion of mul‑ tidrug resistant parasite genotypes, including P. falciparum kelch13 mutations and copy number variation of both P. falciparum plasmepsin 2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes. Results: Validated kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated with piperaquine (PPQ) resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (>30%). Conclusions: These fndings were considered to sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to investigate in vitro susceptibility profles to PPQ of African isolates with multiple copies of the Pfpm2 gene and estimate the risk of development of PPQ resistance in Africa