The clinical epidemiology of scrub typhus in humans, chiggers and rodents

Thesis

Research on the natural history of scrub typhus took place predominantly before the 1970s. This project developed modern techniques to revisit fundamental aspects of the epidemiology and ecology of the disease in Thailand and Laos. Three sites of high scrub typhus disease transmission were identified. Vector chiggers and small mammal hosts were collected, identified and tested for Orientia tsutsugamushi, the causative agent and mapped using GIS. The complex ecological interactions of infected and uninfected vectors and hosts with habitats and seasons were investigated. A low-input targeted enrichment sequencing method was developed and applied to a subset of positive samples. Over 18 months, 244 small mammals and ~17,000 chiggers were tested resulting in 279 O. tsutsugamushi PCR positive samples. Sixty-nine positive human samples were collected. Overall 8.6% of individual chiggers and 25.9% of chigger pools tested positive. At most sites <1% of individual chiggers tested positive, whereas at the 3 highest-risk site 18% were positive. No consistent high-risk area of infection was identified within our study sites (~9km²). High-risk sites were associated with a lower diversity of chigger species, higher proportion of recognized vector species and a higher mean number of chiggers attached to hosts. The end of the dry season was most strongly associated with O. tsutsugamushi positivity. The extremely low quantities of DNA in these samples combined with the complex genome assembly created numerous challenges for sequencing and bioinformatics analysis. Phylogenetic clustering was evident among samples collected from the same sites, although strains with greater genetic differences also appear to co-exist even on the same host. In Thailand and Laos, human infections rise dramatically during the rainy season. However, corresponding proportions of infected chiggers remained stable, suggesting that human behaviour plays a critical role. Improving our understanding of risk behaviour could yield relatively simple interventions to reduce disease acquisition through public health education.

Authors: Elliott, I

• Alternative title: Scrub typhus epidemiology
• DOI: 10.5287/ora-erkbzzekk
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English