Malaria Molecular Epidemiology: An Evolutionary Genetics Perspective

Abstract

Malaria is a vector-borne disease that involves multiple parasite species in a variety of ecological settings. However, the parasite species causing the disease, the prevalence of subclinical infections, the emergence of drug resistance, the scale-up of interventions, and the ecological factors affecting malaria transmission, among others, are aspects that vary across areas where malaria is endemic. Such complexities have propelled the study of parasite genetic diversity patterns in the context of epidemiologic investigations. Importantly, molecular studies indicate that the time and spatial distribution of malaria cases reflect epidemiologic processes that cannot be fully understood without characterizing the evolutionary forces shaping parasite population genetic patterns. Although broad in scope, this review in the Microbiology Spectrum Curated Collection: Advances in Molecular Epidemiology highlights the need for understanding population genetic concepts when interpreting parasite molecular data. First, we discuss malaria complexity in terms of the parasite species involved. Second, we describe how molecular data are changing our understanding of malaria incidence and infectiousness. Third, we compare different approaches to generate parasite genetic information in the context of epidemiologically relevant questions related to malaria control. Finally, we describe a few Plasmodium genomic studies as evidence of how these approaches will provide new insights into the malaria disease dynamics. *This article is part of a curated collection.

FIGURE 1

Phylogeny of Plasmodium parasites based on the mitochondrial genome. The phylogenetic tree shows all the Plasmodium species parasitic to humans, including those that cause zoonotic malarias. Although not a comprehensive phylogeny, it evidences that parasites causing human malaria are not a monophyletic group.

FIGURE 2

Plasmodium life cycle. The Plasmodium haplontic life cycle comprises a vertebrate host and a dipteran vector. In human malarias, an infected female Anopheles mosquito inoculates haploid sporozoites into the host. These sporozoites invade the liver cells and mature into schizonts. The schizonts rupture, releasing merozoites that infect the red blood cells. Some species develop dormant liver stages or hypnozoites that can produce merozoites at a later time (relapse). A fraction of merozoites differentiates into gametocytes (micro- and macrogametocytes). All these stages are haploid. These gametocytes are then taken up by an Anopheles mosquito, in which zygote formation takes place (diploid stage). Due to the nature of the cycle, inbreeding is common. The zygote differentiates into ookinetes and oocysts, the latter with a syncytial cell or sporoblast containing thousands of nuclei in which meiosis takes place, producing haploid sporozoites.

FIGURE 3

Approaches in malaria molecular epidemiology. Shown are techniques and approaches commonly used to generate molecular information in the context of epidemiologic investigations.