UC San Diego

Malaria is the most widespread serious parasitic disease worldwide, with over 2 billion people at risk of infection, over 300 million cases yearly, and over 1 million deaths every year. The primary vector in the Peruvian Amazon, Anopheles darlingi, is a highly anthropophilic rural mosquito. This thesis research focuses primarily on Plasmodium vivax malaria in the Peruvian Amazon, for three reasons: it is the most common form of malaria in the Peruvian Amazon; in comparison with Plasmodium falciparum, Plasmodium vivax malaria is understudied in this region; and the current malaria elimination call to action leads the need for new knowledge on this disease in the Peruvian Amazon. The goal of this thesis research is to contribute with the elimination of malaria transmission by means of testing the overarching central hypothesis that sociodemographics, relapsing Plasmodium vivax malaria, and the use of protein microarray analysis, are current aspects/tools that will help to stopping transmission of Plasmodium vivax malaria within rural villages near Iquitos, and eventually within the Amazon Region of Loreto, Peru. Three studies were conducted and published for this purpose. The first published manuscript analyzes socio- demographical and occupational activities of people at risk for malaria. This analysis allowed us to identify the main risk group among subjects working in the forest or agricultural activities and their partners at home. The second manuscript demonstrated new tools for malaria epidemiology studies: tandem repeat markers and restriction fragment length polymorphism msp3[alpha] markers that have high discriminatory capacity for determining the micro-geography of malaria transmission in the Peruvian Amazon. The third manuscript used genome- level protein microarray analysis to identify new antigens as serological tool to monitor infection status and transmission dynamics, and that proteins recognized by human IgG antibodies are more likely to have amino acid changes or single nucleotide polymorphisms than proteins coded by the genome as a whole, suggesting selection arising from host-pathogen interactions, immune or otherwise. The new P. vivax protein antigens have important potential as tools for sero-epidemiological analysis of surveillance, control and elimination strategies. More generally, these research in the Peruvian Amazon contribute to a better understanding of biological and socio-demographical characteristics of malaria transmission and fundamental properties of the human immune response to Plasmodium vivax