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Title: The molecular epidemiology of Trypanosoma cruzi infection in wild and domestic transmission cycles, with special emphasis on multilocus microsatellite analysis
Author: Llewellyn, Martin S.
ISNI:       0000 0004 2702 4918
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2008
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Trypanosoma cruzi is a zoonotic vector-bome unicellular parasite, with a highly complex silvatic ecology, and native to the Americas. Substantial genetic diversity has been identified in T. cruzi populations, with six phylogenetic groups or Discrete Typing Groups (DTUs) commonly recognised: TCI, TCIIa, TCIIb, TCIIc, TCIId, and TCIIe. The silvatic affinities of these groups are poorly defined, although broad associations between some lineages and distinct ecological niches are recognised. Additionally, a number of studies have demonstrated a degree of within-DTU diversity, and the current classification may be a poor reflection of the total diversity present. In this PhD thesis the genetic diversity of silvatic T. cruzi is examined, in conjunction with a limited number of domestic strains, to investigate the underlying ecological and epidemiological phenomena that dictate the population genetic structure of this parasite. >200 new T. cruzi and Trypanosoma rangeli isolates, including those from silvatic mammals, domestic and peridomestic triatomine bugs, were collected during fieldwork in Venezuela and Bolivia. Where possible, these isolates were genotyped to a DTU level, and the epidemiological significance of these data discussed. Original silvatic genotype data from this study were then compiled with >1000, historical records (1981-2007) for both mammals and triatomines. This dataset was subjected to basic statistical analysis, and strong support found for an association between parasite genotype, silvatic niche, and triatomine vector. Within-DTU genetic diversity was established for ~200 isolates from two widespread silvatic genotypes, TCI and TCIIc, using a genome-wide panel of 49 microsatellite markers, in tandem with sequence analysis. Substantial genetic diversity was identified in both lineages, coincident with weak spatial structuring. The possibility a population bottleneck was investigated within TCI derived from Andean rodent populations. Moreover, the possibility of a bottleneck was also examined in geographically dispersed human TCI isolates taken from lowland Venezuela. Associated epidemiological implications are discussed. Genetic diversity in TCI was additionally examined at a within-host level. A total of 211 clones were taken from eight mammals, and analysed using a subset of microsatellite markers. Again substantial genetic diversity was evident, with stable infection of the same mammal by a number of different stains. Limited evidence of genetic exchange was also observed, but could not be confirmed, and the implications of this are also discussed.
Supervisor: Gaunt, M. W. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral