Project Grant F30AI197454

UNCOVERING THE GENETIC EPIDEMIOLOGY AND TRANSMISSION DYNAMICS OF P. OVALE SPECIES IN THE HUMAN HOST AND MOSQUITO VECTOR IN SUB-SAHARAN AFRICA - PROJECT SUMMARY/ABSTRACT MALARIA IS A MOSQUITO-BORNE, PARASITIC INFECTION CAUSED PRIMARILY BY SIX PLASMODIUM SPECIES. THOUGH THE MAJORITY OF CASES AND DEATHS ARE CAUSED BY P. FALCIPARUM (PF), PARASITES PREVIOUSLY IDENTIFIED AS BELONGING TO THE P. OVALE SPECIES COMPLEX (PO), P. OVALE CURTISI (POC) AND P. OVALE WALLIKERI (POW), ARE UNDERSTUDIED AND UNDERAPPRECIATED CAUSES OF MALARIA IN SUB-SAHARAN AFRICA (SSA) AND IN TRAVELERS TO THE REGION. THEIR UNIQUE BIOLOGY RESULTS IN LOW- PARASITEMIA INFECTIONS AND A POTENTIAL FOR RELAPSE FOR YEARS AFTER PRIMARY INFECTION. THESE FACTORS MAKE THEM CHALLENGING TO CONTROL UNDER CURRENT MALARIA ELIMINATION PARADIGMS, CONTRIBUTING TO CONCERN THAT THEY MAY BECOME A SIGNIFICANT CONTRIBUTOR TO DISEASE IN THE FUTURE. PO COINFECTION WITH PF IS FREQUENTLY OBSERVED IN PO-ENDEMIC SETTINGS AT PREVALENCES MORE COMMON THAN EXPECTED BY CHANCE, AND EVIDENCE FROM COINFECTIONS INVOLVING OTHER PLASMODIUM SPP SUGGEST MULTI-SPECIES INFECTIONS CAN IMPACT PARASITE TRANSMISSIBILITY AND DISEASE VIRULENCE. DESPITE PO'S RELEVANCE TO MALARIA EPIDEMIOLOGY IN SSA, THERE IS REMARKABLY LITTLE UNDERSTANDING OF PO EPIDEMIOLOGY AND TRANSMISSION DYNAMICS. IN THIS RESEARCH TRAINING PLAN, I PROPOSE TO STUDY THE TRANSMISSION DYNAMICS OF PO INFECTIONS IN THE HUMAN HOST AND MOSQUITO VECTOR, USING HIGH RESOLUTION MOLECULAR DIAGNOSTICS AND GENOTYPING. MY PLAN ALSO PROVIDES THE OPPORTUNITY TO INVESTIGATE PF-PO MIXED INFECTIONS AND THE IMPACT OF PARASITE-PARASITE INTERACTIONS ON PARASITE KINETICS AND INFECTION CHARACTERISTICS. TO COMPLETE MY PROPOSED RESEARCH, I WILL LEVERAGE THE BURKINA FASO INTERNATIONAL CENTER OF EXCELLENCE FOR MALARIA RESEARCH (ICEMR), WHICH CONTAINS A MULTI-YEAR LONGITUDINAL HOUSEHOLD-BASED COHORT STUDY AND MOSQUITO XENOSURVEILLANCE STUDY. I WILL CONDUCT MOLECULAR QUANTIFICATION OF PO PARASITEMIA, INCLUDING THE INFECTIOUS GAMETOCYTE STAGES, ON BLOOD SAMPLES SAMPLED FROM COHORT PARTICIPANTS OVER TWO YEARS. COMPLEXITY OF INFECTION AND POPULATION STRUCTURE OF PO INFECTIONS WILL BE CHARACTERIZED USING MULTIPLEXED AMPLICON SEQUENCING. I FURTHER PROPOSE TO INVESTIGATE VECTOR COMPETENCE BY QUANTIFYING PO PREVALENCE IN MOSQUITOES COLLECTED THROUGH THE ICEMR'S XENOSURVEILLANCE EFFORTS; IN ADDITION, I WILL CONDUCT EXPERIMENTAL FEEDING ASSAYS WITH LAB-COLONIZED ANOPHELES FED WITH POC- OR POW- INFECTED BLOOD FROM ICEMR COHORT PARTICIPANTS. BURKINA FASO IS AN IDEAL SETTING FOR THIS STUDY DUE TO ITS BEING HYPERENDEMIC FOR MALARIA, WITH ONGOING SYMPATRIC TRANSMISSION OF NON-FALCIPARUM SPECIES. THIS WORK WILL SIGNIFICANTLY ADVANCE UNDERSTANDING OF THE HOST-PARASITE-VECTOR ASPECTS OF PO EPIDEMIOLOGY AND CONTRIBUTE TO TARGETED MALARIA CONTROL EFFORTS IN THE FUTURE.