Adaptation of Plasmodium falciparum to its transmission environment

Abstract

Success in eliminating malaria will depend on whether parasite evolution outpaces control efforts. Here, we show that Plasmodium falciparum parasites (the deadliest of the species causing human malaria) found in low-transmission-intensity areas have evolved to invest more in transmission to new hosts (reproduction) and less in within-host replication (growth) than parasites found in high-transmission areas. At the cellular level, this adaptation manifests as increased production of reproductive forms (gametocytes) early in the infection at the expense of processes associated with multiplication inside red blood cells, especially membrane transport and protein trafficking. At the molecular level, this manifests as changes in the expression levels of genes encoding epigenetic and translational machinery. Specifically, expression levels of the gene encoding AP2-G-the transcription factor that initiates reproduction-increase as transmission intensity decreases. This is accompanied by downregulation and upregulation of genes encoding HDAC1 and HDA1-two histone deacetylases that epigenetically regulate the parasite's replicative and reproductive life-stage programmes, respectively. Parasites in reproductive mode show increased reliance on the prokaryotic translation machinery found inside the plastid-derived organelles. Thus, our dissection of the parasite's adaptive regulatory architecture has identified new potential molecular targets for malaria control.

Partitioning the influence of ecology across scales on parasite evolution

“…Recent gene expression data from human malaria infections suggest that parasites down‐regulate gametocyte production in regions with high transmission intensity (Rono et al. ), consistent with our model predictions that coinfection and epidemic expansion should select for reduced transmission investment. High transmission intensity confounds epidemiology, frequency of coinfection, and acquired host immune responses, all of which are predicted to select for reduced transmission investment and more aggressive proliferation (e.g., Greischar et al.…”

Two hyperparasitaemic Plasmodium falciparum cases successfully treated with Artemisinin-based Combination Therapy

“…Recent change in the malaria control operations in Mangalore [24] and national malaria control programme [23] have led to a significant reduction in malaria transmission in India. Hypergametocytaemia (54%) with 1:1 of male and female gametocytes ratio in second patient further confirms the hypothesis that in low-transmission areas, parasites invest more in transmission to new hosts via reproduction and less in within-host replication than parasites found in high-transmission areas [25].…”

Two-Faced Immunity? The Evidence for Antibody Enhancement of Malaria Transmission

“…Between 1990 and 2007, slide prevalence of malaria parasites decreased from 68 to 30%, while over the same period the proportion of mosquitoes with sporozoites increased from 5 to 14% [70]. The increased transmission was linked to higher gametocyte biomass in infected individuals, which could occur if commitment rates were driven up by increased expression of the AP2-G protein [71].…”