Genetic diversity of malaria parasite and human host populations in Haiti: Implications for public health policy and practice

Malaria is an infectious disease caused by Plasmodium parasites transmitted by Anopheles mosquito to human. Despite elimination in most developed countries, over 198 million cases were reported in 2013 leading to over 500,000 deaths, making malaria one of the leading causes of deaths in developing countries. Renewed interest in eradication of malaria globally has resulted in reinvigorated questions to understand the biology and evolution of the parasite species. Population health studies on malaria are often paired with investigations into host inherited malaria resistance that is manifested in red blood cell disorders like sickle cell disease and glucose-6-phosphate dehydrogenase (G6PD) deficiency, which evolved in host populations in response to strong selective pressure from malaria. Parasite and host evolution have a major impact on global health, and utilizing information about the characteristics of genetic mutations associated with resistance has important implications for the prevention, diagnostics, and treatment of malaria and associated inherited red blood cell disorders. This dissertation explores these diseases in Haiti, located on the island of Hispaniola, the only malaria endemic island remaining in the Caribbean. The dissertation is broken into two parts: 1) Investigation on antimalarial resistance associated mutations and neutral variation to gain insight into the evolution of the malaria parasite population in Haiti and 2) Investigation into mutations associated with host resistance to malaria, specifically those that confer sickle cell hemoglobin and G6PD deficiency, and comparison of sickle cell genotype data to other methods for screening for sickle cell hemoglobin. For the parasite population, minimal molecular evidence for antimalarial resistance and evidence for a mostly stable parasite population was observed. For the human population, a high frequency of both sickle cell hemoglobin and G6PD deficiency mutations was observed, and best screening methods for these disorders were identified. In conclusion, the potential role that host factors play on malaria parasite evolution in Haiti, including the use or lack of antimalarial drugs and presence of inherited resistance mutations in the host population are discussed. The need for more parasite-host resistance genetic studies and the relevance to the global health initiative to eradicate malaria are also discussed.