SexMal

Duración

Sep 2021 - Aug 2024

Coordinador

Alfredo Mayor

Financiadores

Ministerio de Ciencia, Agencia Estatal de Investigación, Ayuda PID2020-118328RB-I00

Large-scale malaria elimination programs that quickly reduce the malaria parasite biomass in a community can cause strong selection pressures on the parasite population. One of the major evolutionary forces that can determine parasite strategies for survival, growth, or reproduction is the competition between genetically-diverse parasite strains within the host.

Preliminary data in southern Mozambique suggest that the drastic declines in Plasmodium falciparum transmission achieved through an elimination program are associated with reductions in parasite genetic diversity and increases in gametocyte carriage, therefore supporting the concept that Pf can modulate sexual investment to maximize its within-host competitive ability.

Aim and methods

• To test if the Pf reproductive transcriptional program changes after substantial drops in malaria transmission driven by a malaria elimination initiative:
  •  Use qRT-PCR assay to test for enhanced gametocyte production and female-biased ratios in Pf isolates collected from pregnant women in an elimination district (Magude) compared to women residing in a control district (Manhiça).
  • Measure antimalarial antibodies (sexual vs. asexual stages) and lysophosphatidylcholine in plasma samples to discard that differences in gametocyte-specific markers are due to declines in transmission reducing activity or metabolic differences in the human population.
• Analyze Pf whole genome sequences to search for signatures of selection on regulatory regions and coding sequences of genes involved in gametocyte development and test for their association with gametocyte-specific transcriptional patterns.
• Assess if in-host parasite ecology affects gametocyte investment and determine the relationship of gametocyte-specific transcript levels with Pf genetic diversity and relatedness:
  • Testing in vitro the effect of competitive interactions on gametocyte conversion rates and transcriptional program.

Expected Outcomes

Identifying biological mechanisms mediating the adaptive regulation of Pf reproductive investment in response to human interventions that improve the design of optimal approaches for malaria elimination through adequately targeting the transmissible stages.

Total Funding

121,000 EUR