Using whole Plasmodium falciparum genomes for monitoring of escape from diagnosis, drug treatment and vaccine-induced immunity in Central-West Africa

As malaria control programs continue to push for local malaria elimination, novel molecular tools embedded into ongoing surveillance systems are needed. Information generated from molecular methods allows for improved monitoring of parasite drug resistance and diagnostic evasion, therefore helping inform and adapt control strategies. The overall aim of this doctoral work is to use molecular monitoring of P. falciparum, the causative parasite of the most pathogenic form of malaria, to identify hidden reservoirs of the parasite, to monitor for rapid diagnostic test evasion, to understand parasite transmission dynamics and to inform on the next generation vaccine development. Whole genome sequencing data was generated from filter paper blood samples collected within the framework of yearly malaria indicator surveys conducted on Bioko Island, Equatorial Guinea to describe the island’s parasite transmission dynamics. The connectiveness of parasite populations within the island and importation from the African continent is delineated for the first time. A novel, portable PCR device together with a ready to use, lyophilized quantitative PCR assay was deployed locally on Bioko Island at larger scale to detect reservoirs of parasite carriers that potentially contribute to transmission, but evade detection by rapid diagnostic tests. Whole genome sequencing was further utilized to conduct the first whole genome sieve analysis with blood samples collected during a field efficacy study evaluating a whole organism malaria vaccine in West Africa. This sieve analysis identified candidate genes that may encode protective immune targets for next generation malaria vaccines. Ultimately, these molecular methods will allow for improved assessment of ongoing control methods and their impact on parasite populations, providing information for enhanced resource allocation, leading to continued progress towards malaria control and potential local elimination.