SOCIAL ISSUES AND SEX IN P. FALCIPARUM: IMPLICATIONS FOR MALARIA ELIMINATION

Large-scale programs that rapidly reduce malaria parasite biomass in a community can exert strong selective pressures on the parasite population. One of the major evolutionary forces determining parasite survival, growth, or reproduction strategies is competition among genetically diverse parasites within hosts. Evolutionary theory predicts that parasites experiencing conspecific competition within the human host should divert investment in reproduction to maximize replicative capacity that allows them to exploit the most resources (erythrocytes). Therefore, bottlenecks caused by elimination campaigns that reduce the genetic diversity of Plasmodium falciparum (PF) and increase its similarity due to inbreeding and recent common ancestry are expected to affect the balance between asexual growth and transmission.

Preliminary data from southern Mozambique suggest that the dramatic decreases in PF transmission achieved through an elimination program are associated with reductions in parasite genetic diversity and increases in the number of gametocytes produced by infections, thus supporting the concept that PF may modulate investment in sex to maximize its competitive fitness within the host.

For the purpose of this project, the research team will use a gender-specific, multiple-gametocyte-marker, real-time reverse transcription quantitative PCR assay to quantify gametocyte production in PF collected from pregnant women in the elimination district (Magude), compared to women residing in the control district (Manhiça). The investigators will also measure antimalarial antibodies (against both sexual and asexual stages) and lysophosphatidylcholine in plasma samples to rule out whether differences in gametocyte-specific markers are due to decreases in gametocyte-specific immunoactivity or metabolic differences in the human population, respectively.

Second, the researchers will analyze whole-genome sequences of PF to search for signatures of selection in regulatory regions and sequences of genes involved in gametocyte development and test their association with gametocyte-specific transcriptional patterns.

Finally, the team will assess whether parasite ecology in the host affects investment in gametocyte production by determining the relationship of gametocyte-specific transcript levels with the diversity and genetic relatedness of infections, and by testing in vitro the effect of competitive interactions on gametocyte conversion rates and transcriptional programming.

Identifying the biological mechanisms mediating adaptive regulation of PF sexual stage production in response to human interventions may enable the design of optimal strategies for the elimination of transmissible stages of the parasite.

Project details

Basic Science
Genetics and Genomics

Jan 2020

$150,083

Spain