Publication
Clinical malaria incidence following an outbreak in Ecuador was predominantly associated with Plasmodium falciparum with recombinant variant antigen gene repertoires
Publisher:
Cold Spring Harbor Laboratory
Date:
15-04-2021
DOI:
10.1101/2021.04.12.21255093
Abstract: To better understand the factors underlying the continued incidence of clinical episodes of falciparum malaria in E-2020 countries targeting elimination, we have characterised Plasmodium falciparum disease transmission dynamics after a clonal outbreak on the northwest coast of Ecuador over a period of two years. We apply a novel, high-resolution genotyping method, the “ var code” based on a single PCR to fingerprint the DBLα region of the 40-60 members of the variant surface antigen-encoding var multigene family. Var genes are highly polymorphic within and between genomes, with var repertoires rapidly evolving by outcrossing during the obligatory sexual phase of P. falciparum in the mosquito. The continued incidence of clinical malaria after the outbreak in Ecuador provided a unique opportunity to use var codes to document parasite microevolution and explore signatures of local disease transmission on the time scale of months to two years post-outbreak. We identified nine genetic var codes circulating locally with spatiotemporal parasite genetic relatedness networks revealing that ersification of the clonal outbreak parasites by sexual recombination was associated with increased incidence of clinical episodes of malaria. Whether this was due to chance, immune selection or sexual recombination per se is discussed. Comparative analyses to other South American parasite populations where P. falciparum transmission remains endemic elucidated the possible origins of Ecuadorian var codes. This analysis demonstrated that the majority of clinical cases were due to local transmission and not importation. Nonetheless, some of the var codes that were unrelated to the outbreak var code were found to be genetically related to other South American parasites. Our findings demonstrate the utility of the var code as a high-resolution surveillance tool to spatiotemporally track disease outbreaks using variant surface antigen genes and resolve signatures of recombination in an E-2020 setting nearing elimination.