Temporal and spatial dynamics of Plasmodium falciparum clonal lineages in Guyana

• DOI: 10.1371/journal.ppat.1012013
• Publication Date: 2024-06-13T17:57:12Z
• Authors: Mathieu Vanhove; Philipp Schwabl; Collette Clementson; Angela M. Early; Margaret Laws; Frank Anthony; Célia Florimond; Luana Mathieu; Kashana James; Cheyenne Knox; Narine Singh; Caroline O. Buckee; Lise Musset; Horace Cox; Reza Niles-Robin; Daniel E. Neafsey
• Keywords: Piperaquine; Nonsynonymous substitution; Plasmodium (life cycle)

Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. In low transmission settings, parasites recombine with themselves, and clonal lineage is propagated rather than broken up by outcrossing. We investigated whether stochastic/neutral factors drive persistence abundance falciparum lineages in Guyana, a country relatively malaria transmission, but only setting Americas which an important artemisinin resistance mutation (pfk13 C580Y) has been observed. performed whole genome sequencing on 1,727 samples collected from infected patients across five-year period (2016-2021). characterized relatedness between each pair monoclonal infections (n = 1,409) through estimation identity-by-descent (IBD) also typed sample for known or candidate drug mutations. A total 160 multi-isolate clones (mean IBD ≥ 0.90) were circulating Guyana during study period, comprising 13 highly related clusters 0.40). we observed decrease frequency associated partner (piperaquine) (pfcrt C350R) limited co-occurence pfcrt C350R duplications plasmepsin 2/3, epistatic interaction piperaquine resistance. additionally 61 nonsynonymous substitutions increased markedly over as well novel pfk13 (G718S). However, P. dynamics appear to be largely driven stochastic factors, contrast other geographic regions, given carrying polymorphisms do not demonstrate enhanced higher comparable unrelated The use multiple combination therapies may have contributed disappearance C580Y mutation.