Candidate Immediate and Long-term Research Goals: Chandy John is currently a fellow in Pediatric Infectious Diseases/Geographic Medicine at Case Western Reserve University. During the past two years, he has investigated immune responses to the P. falciparum liver-stage antigen-1 in a highland area of Kenya with highly seasonal malaria transmission. His primary areas of interest are the differences in the immune responses of children and adults to P. falciparum antigens and the duration of immune responses to these antigens. The immunological and epidemiologic components of this study represent new approaches for the investigator. Mentored training in these areas will be important to his development as an independent researcher. The proposed study has significant potential for continued future research, specifically comparison of immunity in this area with immunity in a holoendemic area and evaluation of the antigens studied in pilot vaccine trials. The study will provide experience that will enable him to pursue his long-term goal of an academic career with a research focus on the epidemiology of malarial immunity in children and adults. Research Project: Malaria epidemics in highland Kenya may be due in part to prolonged periods of low P. falciparum transmission in the dry season. A consequent decrease in immunologic boosting by P. falciparum antigens may lead to diminished frequencies of the antigen-specific T cells and B cells that maintain partial immunity to malarial infection. The aims of this project are to determine: 1) whether T and B cell responses to P. falciparum antigens are lower in children than in adults in this area, 2) whether these responses decrease in both children and adults during a period of low transmission, and 3)whether diminished responses correlate with increased susceptibility to infection. Two prospective longitudinal studies will compare antigen-specific T and B cell precursor frequencies and antibody levels in groups of 100 adults and 75 children at times of high and low transmission. The second study will be followed by a treatment/reinfection study. All study subjects will be treated with quinine and sulfadoxime/pyrimethamine, and time to reinfection and level of parasitemia at the time of reinfection will be correlated with duration and level of T and B cell responses. An understanding of the relationship of the duration of immune responses to P. falciparum antigens to susceptibility to infection and disease is important in the evaluation of these antigens as malaria vaccine candidates.