Understanding the ecology of Ross River virus; novel approaches and insights into non-human reservoirs

Abstract

Arboviruses contribute a significant burden to human and animal health. Circulation of arboviruses comprises three components; blood-sucking arthropods, vertebrate hosts, and viruses that can infect vertebrates and invertebrates. Interaction of these components is dependent on ecological factors (such as species distributions and climate), epidemiological factors (including vector and host immunity) and behavioural determinants (such as vector feeding host preference or host defensive behaviours). Identifying these drivers of disease emergence can be complicated but informs efforts to mitigate on-going circulation. This dissertation generates new perspectives on the transmission dynamics of Australia’s most common arbovirus, Ross River virus (RRV), with a particular focus on non-human reservoirs. Specifically, I (a) critically analysed current and historic knowledge for non-human reservoirs and vector feeding patterns, (b) examined the natural exposure of RRV in human, free-living and domestic vertebrate populations, and (c) assessed the vertebrate and vector community ecology across areas of varying human notification rates. I began by undertaking a systematic literature review (Chapter 2) assessing evidence for non-human reservoirs of RRV. This chapter synthesised published serological, virus isolation and experimental infection studies in light of the long-held dogma that marsupials are the primary reservoir of RRV. A key finding of this chapter was emerging evidence that placental mammals and birds were also capable of transmitting RRV to mosquito vectors, suggesting a broader reservoir potential than marsupials alone. To further assess the current and historic knowledge, a meta-analysis was performed on mosquito blood meal analysis studies (Chapter 3). It was evident from this chapter that Australian mosquitoes have highly varied feeding patterns which did not reflect their taxonomic classification or larval ecology. To understand the natural exposure of RRV in vertebrate populations I used both existing literature and performed serological surveys. Although humans are largely thought to be RRV dead-end hosts (species which are incapable of pathogen amplification), circulation of the virus in human populations is well documented and provides insights into spatial-temporal patterns of transmission relevant to the understanding of non-human reservoirs. In Chapter 4, I assessed spatial-temporal patterns of seroprevalence in human populations reported from across the natural distribution of RRV in Australia and the Pacific Island Countries from 1958 to present day. A key finding was that RRV circulated in human populations at least since 1975 when human seropositivity between 20 and 34% was reported in Indonesia and Papua New Guinea. This is important because these countries have different vertebrate fauna to Australia, suggesting different transmission cycles. I then assessed RRV exposure in non-human vertebrate species, focussing on South East Queensland, a RRV endemic area (Chapter 5). Samples were collected through a network of veterinary clinics over a 12-month period, and a total 595 samples from 31 species were obtained. The results showed that taxonomic relatedness is not an important determinant for seropositivity, but rather the ecology and physiology of a species including diet, body size and longevity is most important for exposure to RRV. This study not only tests the greatest diversity of vertebrate species in a single RRV seroprevalence study, but is also novel because it provides methodological advances for analysing seroprevalence data for other zoonotic pathogens. In my last data chapter (Chapter 6), I assessed the vertebrate-vector communities across sites with varied RRV human notification rates. Field surveys assessing ‘abundance’ and ‘diversity’ in light of human notifications were undertaken for six months. Human notifications were positively correlated with vertebrate biomass and total mosquito abundance. Although informative in highlighting variables for ongoing investigations, the data from this chapter was insufficient to determine whether this pattern was unique to the specific habitats in which the data was collected, or a true relationship between disease in humans and non-human reservoirs. Nevertheless, this result lends support to the complex transmission dynamics of RRV and the need to apply multi-disciplinary approaches to understand transmission. Throughout the dissertation, I present compelling new evidence that species other than marsupials are involved in the transmission ecology of RRV. My analyses support the notion that transmission is locally dependent on the availability, diversity and ecology of vertebrate hosts, in combination with the diversity and abundance of mosquito vectors. Moreover, by uncovering the feeding patterns of vectors, identifying exposure rates of vertebrate species, in combination with abundance and availability of both vectors and vertebrates, the research in this dissertation provides much of the information required to build a next-generation matrix model for RRV. Throughout the dissertation I have addressed my research aims and present important new methodological techniques (such as combining serological and ecological analyses) for assessing vertebrate reservoirs of arboviruses, whilst carrying out investigations of disease ecology.