Genetic diversity of Plasmodium falciparum in human malaria cases in Mali

Cécile Nabet, Safiatou Doumbo, Fakhri Jeddi, Salimata Konaté, Tommaso Manciulli, Bakary Fofana, Coralie L’Ollivier, Aminata Camara, Sandra Moore, Stéphane Ranque, Mahamadou A. Théra, Ogobara K. Doumbo, Renaud Piarroux

In Mali, Plasmodium falciparum malaria is highly endemic and remains stable despite the implementation of various malaria control measures. Understanding P. falciparum population structure variations across the country could provide new insights to guide malaria control programmes. In this study, P. falciparum genetic diversity and population structure in regions of varying patterns of malaria transmission in Mali were analysed. A total of 648 blood isolates adsorbed onto filter papers during population surveillance surveys (December 2012-March 2013, October 2013) in four distinct sites of Mali were screened for the presence of P. falciparum via quantitative PCR (qPCR). Multiple loci variable number of tandem repeats analysis (MLVA) using eight microsatellite markers was then performed on positive qPCR samples. Complete genotypes were then analysed for genetic diversity, genetic differentiation and linkage disequilibrium. Of 156 qPCR-positive samples, complete genotyping of 112 samples was achieved. The parasite populations displayed high genetic diversity (mean He = 0.77), which was consistent with a high level of malaria transmission in Mali. Genetic differentiation was low (FST < 0.02), even between sites located approximately 900 km apart, thereby illustrating marked gene flux amongst parasite populations. The lack of linkage disequilibrium further revealed an absence of local clonal expansion, which was corroborated by the genotype relationship results. In contrast to the stable genetic diversity level observed throughout the country, mean multiplicity of infection increased from north to south (from 1.4 to 2.06) and paralleled malaria transmission levels observed locally. In Mali, the high level of genetic diversity and the pronounced gene flux amongst P. falciparum populations may represent an obstacle to control malaria. Indeed, results suggest that parasite populations are polymorphic enough to adapt to their host and to counteract interventions, such as anti-malarial vaccination. Additionally, the panmictic parasite population structure imply that resistance traits may disseminate freely from one area to another, making control measures performed at a local level ineffective.