Malarial Ecology, Transmission, Immunology, Parasitology and Prophylaxis in Kenya

Abstract

Abstract : Under this Cooperative Agreement, work focused on Malaria Immunolgy and vaccine development, microbiology and drug development and vector studies. The recombinant RTSS circumsporozoite vaccine was tested and showed to be efficacious but waranted further studies. Field site development continued in Western Kenya in preparation for future more effective vaccine candidates. In between vaccine trials basic immunological research was undertaken which led to novel hypotheses for the increased risk of primigravida mothers to malaria complications and the propensity of children in regions with hyperendemic malaria such as in Nyanza province to present with severe anemia. Phase 1 and 2 drug studies were undertaken leading to filing of an NDA for oral atovaquone/proguanil for the treatment of uncomplicated falciparum malaria and the identification of a promising long acting 8-amino quinoline for malaria prophylaxis. The effectiveness of antimalarial regimens routinely used in Kenya were evaluated in in vitro drug sensitivities studies. Results from these studies have led to re-evaluation of the national recommendations for first and second-line drug use in the country. Additional work was performed in the area Plasmodial drug resistance and the foundation set for surveillance studies to determine the distribution of drug resistance genes, in particular DFHR point mutations in the region. An automated in vitro drug sensitivity system was successfully established during the closing months of this contract. The prevalence of antibiotic resistance in enteric pathogens was also determined during the course of this CA. Surveys were undertaken in Machakos, Entosopia and Mathere 4B with surprising results that may impact the future antibiotic use in specific communities within the country.