Malaria Epidemiology at the Clone Level

Abstract

Genotyping to distinguish between parasite clones is nowadays a standard in many molecular epidemiological studies of malaria. It has become crucial in drug trials and to follow individual clones in epidemiological studies, and to understand how drug resistance emerges and spreads. Here, we review the applications of the increasingly available genotyping tools and whole-genome sequencing data, and argue for a better integration of population genetics findings into malaria-control strategies.

Keywords: SNP; drug resistance; microsatellite; parasite migration; relapse; whole-genome sequencing.

Figure 1. Parasite population structure and malaria control

Dots of similar colors represent genetically related parasites, while dots of different color represent unrelated parasites. Arrows represent suspected parasite migration patterns. A) Limited gene flow between parasite populations, and as the result genetically different populations, suggests that after successful malaria elimination in one region the risk of re-introduction is small. Such analysis is usually done on the region to country level, e.g. parasites populations in different provinces might be compared and provinces for elimination identified. B) Population structure assuming that parasites spread from foci of high transmission (represented by large dots) to surrounding areas. In the example malaria control targeted towards the first focus (in red) would be expected to reduce transmission to the close surroundings with genetically similar parasites, but would not have an impact on the second focus (in blue), containing genetically different parasites. Foci of transmission would be small (e.g. a homestead), and parasite spread is expected across a few kilometers. C) Outbreak caused by an imported case to a previously malaria-free region, resulting in clonal population structure (top), vs. ongoing transmission of a genetically diverse population (bottom).

Figure 2. Initial blood-stages and relapses of genetically diverse parasites

Possible pattern of blood-stage parasites in an individual with multiple mosquito bites and relapses. After the initial inocula of genetically related sporozoites resulting from meiotic recombination, the primary infection and subsequently the first relapse are related and share most alleles. After a second inocula of an unrelated clone, and a second relapse of the first inocula, two unrelated clones can be detected in the blood stream.