The deafening silence of Plasmodium falciparum asymptomatic infections
Malaria in The Gambia is seasonal, with virtually all cases occurring during or just after the four month-long wet season. As there is very little transmission during the dry season, the reservoir for Plasmodium falciparum parasites is thought to be within asymptomatic chronic infections. How the parasite can survive in the same human host for more than 8 months is not understood.
Dr Claessens and his team first conducted a longitudinal study in 1500 participants in the Upper River Region of The Gambia from 2014 to 2017 over 16 timepoints. In total, 436 P. falciparum positive samples, mainly from asymptomatic infections, were successfully genotyped with 89 SNPs. Average identity by descent (IBD) between different infection genotypes was very low even within a single local village, but isolates from the same household were three times more likely to be genetically related than those from elsewhere within the village. Parasites isolated during the dry seasons showed higher IBD relatedness to those from the previous wet season than to the following one, showing that haplotype diversity is renewed during every wet season.
Secondly, this research recruited 17 carriers who remained asymptomatically infected with P.falciparum for over 6 months during the dry season. Using long-read and short-read sequencing technologies, the parasite genome and transcriptome of these parasites is being characterised at each monthly timepoint, with a particular focus on variant surface antigens (var/rif/stevor).
Biochemist by training, his malaria research career started when Antoine was awarded a Wellcome Trust PhD at Edinburgh University, during which he discovered that P. falciparum group-A var genes were necessary for binding to endothelial cells in an in vitro model for cerebral malaria. During his post-doc at the Sanger Institute, Antoine showed how mitotic ectopic recombination creates new “chimeric” var genes using next-generation sequencing tools. He was then awarded an MRC fellowship based at the London School of Hygiene & Tropical Medicine (LSHTM) and at the MRC-Gambia for a Plasmodium falciparum population genomic study. From the bench to bioinformatics via the bush, Antoine is now an all-rounder malariologist starting his own group (GATAC-Malaria) as a Chargé de Recherche Inserm at LPHI and MIVEGEC, Montpellier, France.