Much Needed Studies of the Three Players of Chagas Disease in Central America: Vertebrate Blood Meal Sources and EcoHealth, a New Vector Species Description, and Key Phylogenetic Analysis of the Trypanosome Parasite

摘要

The protozoan parasite Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae) is the etiological agent of Chagas disease, reported by the World Health Organization (WHO) as responsible for over 10,000 deaths in 2015. Chagas disease is considered a Neglected Tropical Disease by the WHO, this designation highlights the challenges to overcoming the disease as it afflicts the most vulnerable populations, mainly the rural poor in Latin America. Understanding T. cruzi transmission dynamics is particularly difficult because it can be vectored by over 150 species of Triatominae insects, and all mammal species are potential hosts. Thus, results from one locale may not be generalizable to other regions. Chagas disease was discovered in Brazil by Carlos Chagas (1909) over a century ago, yet there is still a serious lack of information from North America (NA) and Central America (CA); the majority of vector and parasite research is focused on South America. The research presented in this dissertation addresses the three main players with respect to the gap of information from NA and CA. I used entomological information along with a variety of molecular tools (i.e. from conventional PCR to genome wide sequencing) and a diversity of genetic markers (i.e. the nuclear internal transcribed spacer (ITS-2), the mitochondrial cytochrome b (cytb), among others) in three studies. The first evaluated base-line ecological conditions in three regions of Central America prior to Ecohealth interventions designed to reduce human-parasite contact. The second described and characterized a new species of insect vector, Triatoma huehuetenanguensis. The third, investigated the evolutionary history and population genetics of the major T. cruzi genetic lineages circulating across NA and CA regions. The results of the first study stress the importance of considering local conditions for vector control success. The second study highlights that undescribed vector species represent a challenge to vector control strategies. The third study showed three major genetic lineages circulating across NA and CA that are distinct from South America, a finding that is fundamental not only for drug development, but to develop accurate diagnostic tools and to understand clinical outcomes of the disease in the region. The population genetic analysis of samples from Guatemala and El Salvador revealed that genetic diversity has a geographic component with parasite movement occurring at both large and small geographic scales, with important implications for the epidemiology of Chagas disease.