Academic literature on the topic 'Ross River Virus'

Sera from twelve species of native and five species of introduced mammals collected on the south coast of New South Wales between 1982 and 1988 were tested for antibodies to the following arboviruses: Ross River virus (621 animals tested); Barmah Forest virus (371); Gan Gan virus (337); Trubanaman virus (378). Serum neutralising antibodies to Ross River virus were found in bandicoots, wallabies, kangaroos, cattle, goat and horses; to Barmah Forest virus in kangaroo, cattle and horses; to Gan Gan virus in kangaroos, wallabies, rat, cows, horses and sheep; and to Trubanaman virus in kangaroos, wallabies, cows and horses. Titres to Ross River virus in seropositive native animal sera ranged from 32 to 1024 and those in seropositive domesticated animal sera ranged from 8 to 32 768. Prevalence of serum antibodies in macropodids, cattle and horses was: Ross River virus, 68, 19, 62%; Barmah Forest virus, 4, 26, 9%; Gan Gan virus, 44, 13, 13%; Trubanaman virus, 60, 3, 10% respectively. Evidence suggests that: (1) kangaroos and wallabies are major vertebrate hosts for Ross River virus; (2) the role of bandicoots warrants further investigation; (3) horses may be important amplifying hosts of the virus, which causes epidemic polyarthritis in man in Australia.

ABSTRACT Glycoprotein PE2 of Sindbis virus will form a heterodimer with glycoprotein E1 of Ross River virus that is cleaved to an E2/E1 heterodimer and transported to the cell plasma membrane, but this chimeric heterodimer fails to interact with Sindbis virus nucleocapsids, and very little budding to produce mature virus occurs upon infection with chimeric viruses. We have isolated in both Sindbis virus E2 and in Ross River virus E1 a series of suppressing mutations that adapt these two proteins to one another and allow increased levels of chimeric virus production. Two adaptive E1 changes in an ectodomain immediately adjacent to the membrane anchor and five adaptive E2 changes in a 12-residue ectodomain centered on Asp-242 have been identified. One change in Ross River virus E1 (Gln-411→Leu) and one change in Sindbis virus E2 (Asp-248→Tyr) were investigated in detail. Each change individually leads to about a 10-fold increase in virus production, and combined the two changes lead to a 100-fold increase in virus. During passage of a chimeric virus containing Ross River virus E1 and Sindbis virus E2, the E2 change was first selected, followed by the E1 change. Heterodimers containing these two adaptive mutations have a demonstrably increased degree of interaction with Sindbis virus nucleocapsids. In the parental chimera, no interaction between heterodimers and capsids was visible at the plasma membrane in electron microscopic studies, whereas alignment of nucleocapsids along the plasma membrane, indicating interaction of heterodimers with nucleocapsids, was readily seen in the adapted chimera. The significance of these findings in light of our current understanding of alphavirus budding is discussed.

Ross River virus (RRV) is a mosquito-borne alphavirus and the aetiological agent of epidemic polyarthritis (EPA). Arthropod borne-Alphaviruses that are related to RRV, such as Chikungunya virus, Sindbis virus and Barmah Forest virus, are usually associated with epidemics of infectious arthritides in different parts of the world. In humans, RRV-induced disease symptoms include fever, rash, myalgia and pain and stiffness of the joints. Muscle and joint pain are the most debilitating symptoms in RRV patients and the best treatment available is non-steroidal anti-inflammatory drugs (NSAID). Previous studies in mice have demonstrated that RRV infection results in inflammation of skeletal muscle and joints and that macrophages play a primary role in disease. The present study was carried out to further elucidate the underlying mechanisms mediating RRV-induced muscle and joint pathology. Previous studies have reported that encephalitic alphaviruses trigger apoptosis of brain cells in mice and that blocking apoptosis reduces mortality rates. In the present study, the ability of RRV to induce muscle apoptosis was investigated in vitro, using a murine myoblast cell line (C1C12), and in vivo, using a mouse model of RRV disease. RRV-infected C1C12 myofibres displayed an array of morphological and biochemical makers of apoptosis. Apoptosis was also observed in the skeletal muscle of RRV-infected C57BL/6J mice. Blocking apoptosis by general caspase inhibition resulted in milder disease symptoms, reduced myofibre damage and decreased inflammation of muscle and joint tissues. The total number of cell infiltrates as well as the number of macrophages infiltrating muscle was significantly reduced by the treatment with a caspase inhibitor. The effects of RRV infection on the skeletal system were also investigated. Primary human osteoblast cells were infected with RRV and monitored for viral-induced cytopathic effect. Osteoblasts supported rapid virus growth and, by 48 hours after infection, succumbed to viral-induced necrosis. In addition, histological examination of bone tissue from RRV-infected C57BL/6J mice showed clear evidence of bone resorption. Tibias from infected mice showed an increased number of activated osteoclasts, a reduction in bone density and thinning of cortical bone. The expression of host factors involved in inflammatory responses and bone remodelling was studied in RRV-infected myofibres and osteoblast cell cultures and in the muscle and joint tissues from infected mice. RRV-infected muscle cells and tissue showed elevated mRNA levels for the chemokines CCL-2, CCL3, CCL5 and CXCL1, all of which are known to mediate the migration of monocytic cells. With the exception of CXCL1, these chemokines were also found to be up-regulated in RRV-infected osteoblast cultures and in joint tissues from infected mice. Muscle and joint tissue from infected mice also showed elevated mRNA levels for type I and type II interferons, TNF- and NOS2. In addition, joint tissues from infected animals contained high levels of IL-6 and IL-1, two cytokines known to mediate bone remodelling. Finally, the therapeutic potential of the drug bindarit was investigated using the mouse model of RRV disease. Bindarit is a known inhibitor of CCL-2 and TNF- and has been found to prevent protein denaturation. Treatment with bindarit resulted in mice developing milder disease symptoms, reduced muscle damage and decreased inflammation of muscle and joint tissues. In particular, bindarit significantly reduced macrophage infiltration into skeletal muscle tissue. This thesis has contributed to the understanding of RRV pathogenesis. It has identified novel mechanisms of RRV-induced muscle and bone pathology and provided further evidence that associate pro-inflammatory host factors to RRV disease. This work has also demonstrated that bindarit should be considered as a candidate for treating RRV disease in humans.

Ross River virus is one of the most severe communicable diseases in Australia. During the 1995/96 outbreak of Ross River virus in south-western Australia, over 1 ,300 human cases were reported. Since the symptoms of the disease are sometimes too weak to be diagnosed, it is important to determine the number of humans who actually contracted the virus during outbreaks. To do this, several mathematical models with different hypotheses are constructed and analysed mathematically. The threshold mathematical conditions of these models suggest that as well as the size of the vector mosquito population, the population size and length of viraemia periods; of host populations and the infection rates between the hosts and vectors play the main roles in the transmission. Several parameters in the transmission are currently unknown, so only simple models of RRV transmission are computer-simulated. Some of the unknown parameters are extrapolated from published studies of other arboviruses. The sensitivities of the models to some of the unknown parameters are also examined. Simulation results indicate the sero-conversion rates and ratios of clinical to subclinical human infections during the outbreaks which occurred in the Peel and Leschenault districts in Southwestern Australia.

[Truncated abstract] Ross River virus (RRV) causes the most common arboviral disease in Australia, with approximately 5000 new cases reported each year, making this virus a major public health concern. The aim of this thesis was to link results from virological, pathogenesis and epidemiological studies to further define RRV disease in the south-west (SW) of Western Australia (WA), a region of endemic and epizootic RRV activity. A crosssectional seroprevalence study was used to show that 7.8 percent of SW communities were seropositive to RRV, comparable to other regions of Australia with similar temperate climates to the SW . . . RRV-specific IgM antibodies were found to persist for at least two years following RRV infection. A murine model was used to conclusively show differences in pathogenesis between RRV genotypes, the SW and northern-eastern (NE) genotypes, which are known to circulate throughout Australia. The SW genotype, unique to the SW of WA induced only poor neutralising antibody production and nonneutralising antibodies after the acute phase of infection. In comparison, the NE genotype which currently predominates in mosquito populations in the SW of WA, induced the most efficient neutralising antibody response and consequently produced the mildest disease in the mouse. These data in the mouse suggest that the infecting genotype will mostly likely influence disease outcome in humans and could at least partially explain why more severe and persistent disease has been reported from the SW of WA. Collectively, results from this thesis provide an important benchmark against which future investigations into BFV and RRV diseases can be measured.

Ross River virus (RRV) is an Alphavirus distributed throughout Australia. It is transmitted by mosquitoes and is known to cause moderate to severe disease symptoms in humans. Along with other alphaviruses such as Sindbis virus and Chikungunya virus, RRV is known to cause arthritic symptoms, characterised by muscle and joint inflammation. Several investigations have established the role of macrophage cells and pro-inflammatory host factors in the development of RRV-induced disease. In this study, we attempted to determine differences between RRV passaged in mammalian and mosquito cells. There is strong evidence that arthropod-borne viruses are able to display enhanced infectivity when passaged into arthropod cell line. We showed that mosquito cell-derived RRV (mos-RRV) was able to replicate to higher titres than mammalian cell-derived RRV. We also showed that mos-RRV failed to induce Type I IFN-associated antiviral responses. The second aim of this study was to investigate the role of TNF-ᬠa pro-inflammatory cytokine implicated in arthritic diseases, in the development of RRV disease. We treated RRV-infected C57BL/6J mice with a commercially available TNF-ᠩnhibitor drug and monitored disease signs. We found that the TNF-ᠩnhibitor does not ameliorate RRV disease (RRVD) symptoms, and that it does not prevent muscle and joint inflammation. We analysed histological sections of muscle and joint tissue of Enbrel-treated and untreated, RRV-infected cells. We also determined and compared host cytokine expression profiles. Finally, we sought to determine the requirement for natural killer (NK) cells in RRV disease. NK cells have been detected in the synovium of RRV-infected patients since early studies, but their role in disease pathogenesis remains unclear. Using a NK-dysfunctional mouse (C57BL/6J-Lystbg), we showed that mice lacking a functional NK system are more susceptible to RRV disease than wildtype, C57BL/6J mice. We monitored disease symptoms following RRV infection and assessed muscle and joint inflammation in Lystbg and C57BL/6J mice. This thesis examines mechanisms of viral infection and immune evasion employed by RRV, as well as into the role of host cells and cytokines in RRVD pathogenesis disease mechanisms. We showed that a functional NK cell system is required for the regulation of RRV-induced muscle and joint inflammation. Our characterisation of the use of a commercial TNF-ᠩnhibitor in RRV-induced disease in mice may provide information on the role of TNF-ᠩn viral arthritis, and may help towards developing safe and effective treatment.

Ross River virus (RRV) belongs to the genus Alphavirus and is a medically important arbovirus that causes musculoskeletal disease in humans with symptoms such as arthralgia, arthritis and myalgia. Disease symptoms consistent with RRV infection were first recorded in 1928 in Australia. Currently, with approximately 5,000 cases of RRV infection reported each year in Australia, RRV is the most widely spread arbovirus throughout the South Pacific region. At present there are no specific therapeutics or vaccines available. RRV disease is treated with analgesics and non-steroidal anti-inflammatory drugs to provide symptomatic relief. Therefore, it is important to investigate RRV disease mechanisms so as to better understand disease pathogenesis, which could lead to identifying potential targets for therapeutic intervention. The host Type I interferon (IFN) system is the primary innate antiviral defence mechanism. The antiviral effects of type I IFN act to both suppress viral replication and modulate innate and adaptive immune responses during viral infection. However, the interplay between the host type I IFN responses and alphavirus infection is currently poorly understood. This thesis focuses on the role of type I IFN system in RRV infection and disease pathogenesis.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
Science, Environment, Engineering and Technology
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The physical and immunological consequences to BALB/c and CBA murine neonates of in utero infection with Ross River virus [RRV] were compared to previously reported teratogenic and tolerogenic properties of other togaviruses. X-ray imaging as a means of determining the incidence, type and extent of teratogenesis induction in neonatal mice lacked sufficient resolution for the determination of structural abnormalities. A previously described histological technique for identifying cartilage and bone defects [Mabruk et al., 1988] was unsatisfactory as disintegration of neonatal material occurred upon storage. This study modified the method to include an inital fixation step in normal buffered formalin prior to Alcian Blue staining, a ten-fold increase in the concentration of the clearing agent and an extension of reagent exposure times. No skin defects nor skeletal deformities, reported in similar studies with related viruses, were noted in the present investigation. Skeletal changes observed following embryonic exposure to RRV at 8 to 18 days gestation were similar to those seen in uninfected control mice. Such changes, which included bones missing or not visible in the extremities of mice, were attributed to incomplete skeletal development resulting from variations both in the murine gestational period [19 to 21 days] and in the collection of neonates post-partum [within 12 hours of birth]. Changes to the structure [malformation] and orientation [misalignment] of the sternebrae, noted in the present investigation, were considered variable but normal representations of ossification centres within the sternum. No difference in the incidence or severity of these anatomical disturbances was observed between uninfected and RRV infected mice in this study. Although the development of six bones within the sternum were expected, 6% [5/83] of neonatal BALB/c mice demonstrated a supernumerary sternebra. This observation was not significant for uninfected and RRV-infected populations. Further, one uninfected CBA mouse presented with only five sternebrae. Consequently, it is concluded that in utero exposure to RRV, strain T48, does not induce teratogenic changes to BALB/c or CBA foetuses. The induction of neonatal immunological tolerance in uninfected mice and mice exposed in utero to RRV was assessed using an indirect enzyme linked immunosorbent assay [ELISA] to quantify the murine serum titres of anti-RRV lgM and lgG subclass antibodies. Further, a virus titration method was utilised to assay murine sera for virus content. Four experimental groups of mice were investigated : U and I defined as uninfected and infected respectively; 0 and M defined as offspring and mother respectively. Serum titres of anti-RRV lgM antibody remained similar or increased significantly during the testing period. In contrast, the serum titres of anti-RRV lgG antibodies were obseNed to significantly increase only in those offspring suckled on uninfected mothers [U0UM and l0UM groups] and to significantly decrease only in those offspring suckled on infected mothers [U0 1M and 10 1M groups]. Further, a significant reduction in the incidence of viraemia and median serum titre of virus was obseNed only in BALB/c mice born to, and subsequently suckled on, uninfected mothers. For both BALB/c and CBA mouse strains, comparisons between groups of mice [U0 UM and 10 UM; U0 1M and 10 1J indicated that the serum titres of anti-RRV lgG subclass and lgM antibodies remained similar or were significantly elevated in the uninfected offspring during the 2 week period following intraperitoneal [i.p.] injection with RRV. Other comparisons [U0UM and U0 1M; 10 UM and 10 1J indicated that although the serum titres of anti-RRV lgG subclass antibodies were similar or significantly elevated in those mice suckled on infected mothers at 1 and 3 days following i.p. injection, this trend was reversed at 14 days post-injection. For these same comparisons, serum titres of RRV-specific lgM antibody remained similar or were significantly higher in those mice suckled on uninfected mothers for the entire testing period. In addition, more offspring born to, and subsequently suckled on, uninfected mothers were viraemic, with significantly higher serum titres of virus, than any other experimental group. Generally, inter-strain comparisons for each experimental group indicated that serum titres of anti-RRV antibodies were either similar in both mouse strains or significantly elevated in CBA mice. Significant variation in the incidence of viraemia and median serum titre of virus was observed only in those mice born to, and subsequently suckled on, uninfected mothers. At 3 days post-injection, more CBA mice were viraemic, with higher serum titres of virus, than BALB/c mice. Post-partum transfer of maternal immunoglobulin moderated the lgG and lgM immune responses in uninfected mice suckled on infected mothers, affirming the importance of maternal antibody in neonatal anti-viral protection. This investigation presents important information on the effects of in utero exposure to RRV in the murine model. A distinct deficiency in lgG production was demonstrated in mice infected in utero with virus then challenged postpartum. Further characterisation of this immunodeficiency indicated that all the lgG pathways in BALB/c mice were affected, while in CBA mice only the lgG1 and lgG3 subclasses were reduced. No correlation between prenatal exposure to RRV and lgM production was evident. These results provide the first evidence for the induction of neonatal immunological tolerance in BALB/c and CBA mice following in utero exposure to RRV. This thesis proposes clonal anergy of B cells, capable of responding to RRV, as the primary mechanism responsible for the immunologically non-responsive state observed in this study. However, the ancillary role of clonal abortion of RRV-specific Band T cell clones in the induction of murine neonatal tolerance cannot be dismissed. The future investigation of specific aspects identified in this study are of considerable importance in vaccine development. The possibility of adverse effects of a live vaccine on an unborn child would greatly affect the decision as to whether a RRV vaccine should be live attenuated or killed.

[Truncated abstract] In an era of emerging and resurging infectious diseases, understanding the ecological processes that influence pathogen activity and the influences of anthropogenic change to those are critical. Ross River virus (RRV, Togoviridae: Alphavirus) is a mosquito-borne zoonosis occurring in Australia with a significant human disease burden. In the southwest of Western Australia (WA) RRV is principally vectored by Aedes camptorhynchus Thomson (Diptera: Culicidae), which is halophilic. The inland southwest, the Wheatbelt region, of WA is substantially affected by an anthropogenic salinisation of agricultural land called dryland salinity, which threatens to influence transmission of this arbovirus. This study assessed the ecological impacts of dryland salinity on mosquitoes, mammalian hosts and their interactions to influence the potential for RRV transmission. Many aquatic insect taxa colonise ephemeral water bodies directly as adults or by oviposition. Using a manipulative experiment and sampling from ephemeral water bodies in the Wheatbelt, I demonstrated that salinity of water bodies can modify colonisation behaviour and the distribution of some organisms across the landscape. Halosensitive fauna selected less saline mesocosms for oviposition and colonisation. In particular, Culex australicus Dobrotworksy and Drummond and Anopheles annulipes Giles (Diptera: Culicidae), potential competitors with Ae. camptorhynchus, avoided ovipostion in saline mesocosms and water bodies in the field. This finding suggests salinity influences behaviour and may reduce interspecific interactions between these taxa and Ae. camptorhynchus at higher salinities. Using extensive field surveys of ephemeral water bodies in the Wheatbelt I found mosquitoes frequently colonised ephemeral water bodies, responded positively to rainfall, and populated smaller water bodies more densely than larger water bodies. The habitat characteristics of ephemeral water bodies changed in association with salinity. Consequently there were both direct and indirect associations between salinity and colonising mosquitoes. Ultimately the structure of mosquito assemblages changed with increasing salinity, favouring an increased regional distribution and abundance of Ae. camptorhynchus. The direct implication of this result is secondary salinisation has enhanced the vectorial potential for RRV transmission in the WA Wheatbelt. ... This thesis contributes to an emerging body of research aimed at delineating important ecological processes which determine transmission of infections disease. Collectively the findings in this study suggest dryland salinity enhances the potential for RRV activity in the Wheatbelt. Currently, human RRV notifications in the Wheatbelt do not reflect the salinity-RRV transmission potential in that area, but appear to be associated with dispersal of RRV from the enzootic coastal zone of southwest WA. I speculate dryland salinity is a determinant of potential for RRV transmission, but not activity. Dryland salinity is predicted to undergo a two to four fold expansion by 2050, which will increase the regional potential for RRV activity. Preservation and restoration of freshwater ecosystems may ameliorate the potential for transmission of RRV and, possibly, human disease incidence.

Insect pests (such as mosquitoes) and their associated impacts have become important social, economic and environmental health issues. Mosquitoes transmit diseases, are widely perceived as a nuisance and are becoming a serious health concern for the public. The incidence of contracting mosquito-transmitted diseases has markedly increased in recent decades in Australia (Russell 1994). Currently, Ross River virus is the most prevalent mosquito-transmitted viral disease in Australia with up to 8,000 cases reported annually (Curran et al. 1996). The absence of documented evidence about the full social costs of mosquito-transmitted diseases is a critical issue as there is currently no economic rationale underlying existing resource allocation for intervention programs. This study of the full social costs of Ross River virus was conducted between April and July 2002. Demographic, health-state and disease-related data were collected using survey questionnaires for 201 notified Ross River virus victims from across Queensland. Two self-administered surveys were conducted at the time approximately onset and six months from onset while a phone survey was conducted at 12 months after onset. Direct impacts such as the costs of health care (medical consultations, pathology services and medicines), non health care resources (treatment-related transport) and indirect impacts such as the opportunity cost of lost productivity (due to disability and treatment-related waiting times) of the viral illness were recorded in the questionnaires and were valued using market prices. A non-market valuation method (willingness-to-pay), in conjunction with a self-assessed standard health measure (Short Form 36) were used to quantify more intangible health-related quality of life effects such as change in physical, mental and social functioning. Estimated full social costs of the disease were analysed across age and gender groups. Based on the mean cost estimates for the study sample, the total disease costs have been extrapolated by local government areas as the appropriate administrative areas. A wide range of social and economic costs of the virus has been addressed in this thesis. However, the derived costs cannot be summed into a total estimate as several of these values overlap in terms of coverage. Therefore, only the major cost components, with a minimum of overlap, have been used to estimate the aggregate social cost of the disease. Given the methodological and empirical limitations of the study, the most accurate estimate of the average per capita full costs of Ross River virus in Queensland is estimated at $AUD (2002) 1,070 per case. The estimate of the full social cost of Ross River virus disease can be a vital input for many relevant policy applications. For example, disease costs together with resource costs of current interventions, are essential inputs for ongoing economic evaluations of mosquito control programs at local level. In this thesis, the cost minimisation approach has been presented to evaluate mosquito control programs at the local level where the policy analyst’s task is to minimise the overall social costs (that is, disease costs plus control costs). These economic evaluations have substantial potential benefits to society in terms of the efficient allocation of scarce resources. In addition, estimated disease cost is a significant input for economic impact assessment of regional disease outbreaks. It also can be used to highlight disease impact upon the economy and community and hence draw attention to the scale and scope of such problems to policy makers at all levels so that they can respond appropriately to the mosquito problem, and mosquito-transmitted diseases, as priority issues in the political agenda.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Australian School of Environmental Studies
Science, Environment, Engineering and Technology
Full Text

The incidence of many arboviral diseases is largely associated with social and environmental conditions. Ross River virus (RRV) is the most prevalent arboviral disease in Australia. It has long been recognised that the transmission pattern of RRV is sensitive to socio-ecological factors including climate variation, population movement, mosquito-density and vegetation types. This study aimed to assess the relationships between socio-environmental variability and the transmission of RRV using spatio-temporal analytic methods. Computerised data files of daily RRV disease cases and daily climatic variables in Brisbane, Queensland during 1985-2001 were obtained from the Queensland Department of Health and the Australian Bureau of Meteorology, respectively. Available information on other socio-ecological factors was also collected from relevant government agencies as follows: 1) socio-demographic data from the Australia Bureau of Statistics; 2) information on vegetation (littoral wetlands, ephemeral wetlands, open freshwater, riparian vegetation, melaleuca open forests, wet eucalypt, open forests and other bushland) from Brisbane City Council; 3) tidal activities from the Queensland Department of Transport; and 4) mosquito-density from Brisbane City Council. Principal components analysis (PCA) was used as an exploratory technique for discovering spatial and temporal pattern of RRV distribution. The PCA results show that the first principal component accounted for approximately 57% of the information, which contained the four seasonal rates and loaded highest and positively for autumn. K-means cluster analysis indicates that the seasonality of RRV is characterised by three groups with high, medium and low incidence of disease, and it suggests that there are at least three different disease ecologies. The variation in spatio-temporal patterns of RRV indicates a complex ecology that is unlikely to be explained by a single dominant transmission route across these three groupings. Therefore, there is need to explore socio-economic and environmental determinants of RRV disease at the statistical local area (SLA) level. Spatial distribution analysis and multiple negative binomial regression models were employed to identify the socio-economic and environmental determinants of RRV disease at both the city and local (ie, SLA) levels. The results show that RRV activity was primarily concentrated in the northeast, northwest and southeast areas in Brisbane. The negative binomial regression models reveal that RRV incidence for the whole of the Brisbane area was significantly associated with Southern Oscillation Index (SOI) at a lag of 3 months (Relative Risk (RR): 1.12; 95% confidence interval (CI): 1.06 - 1.17), the proportion of people with lower levels of education (RR: 1.02; 95% CI: 1.01 - 1.03), the proportion of labour workers (RR: 0.97; 95% CI: 0.95 - 1.00) and vegetation density (RR: 1.02; 95% CI: 1.00 - 1.04). However, RRV incidence for high risk areas (ie, SLAs with higher incidence of RRV) was significantly associated with mosquito density (RR: 1.01; 95% CI: 1.00 - 1.01), SOI at a lag of 3 months (RR: 1.48; 95% CI: 1.23 - 1.78), human population density (RR: 3.77; 95% CI: 1.35 - 10.51), the proportion of indigenous population (RR: 0.56; 95% CI: 0.37 - 0.87) and the proportion of overseas visitors (RR: 0.57; 95% CI: 0.35 - 0.92). It is acknowledged that some of these risk factors, while statistically significant, are small in magnitude. However, given the high incidence of RRV, they may still be important in practice. The results of this study suggest that the spatial pattern of RRV disease in Brisbane is determined by a combination of ecological, socio-economic and environmental factors. The possibility of developing an epidemic forecasting system for RRV disease was explored using the multivariate Seasonal Auto-regressive Integrated Moving Average (SARIMA) technique. The results of this study suggest that climatic variability, particularly precipitation, may have played a significant role in the transmission of RRV disease in Brisbane. This finding cannot entirely be explained by confounding factors such as other socio-ecological conditions because they have been unlikely to change dramatically on a monthly time scale in this city over the past two decades. SARIMA models show that monthly precipitation at a lag 2 months (=0.004,p=0.031) was statistically significantly associated with RRV disease. It suggests that there may be 50 more cases a year for an increase of 100 mm precipitation on average in Brisbane. The predictive values in the model were generally consistent with actual values (root-mean-square error (RMSE): 1.96). Therefore, this model may have applications as a decision support tool in disease control and risk-management planning programs in Brisbane. The Polynomial distributed lag (PDL) time series regression models were performed to examine the associations between rainfall, mosquito density and the occurrence of RRV after adjusting for season and auto-correlation. The PDL model was used because rainfall and mosquito density can affect not merely RRV occurring in the same month, but in several subsequent months. The rationale for the use of the PDL technique is that it increases the precision of the estimates. We developed an epidemic forecasting model to predict incidence of RRV disease. The results show that 95% and 85% of the variation in the RRV disease was accounted for by the mosquito density and rainfall, respectively. The predictive values in the model were generally consistent with actual values (RMSE: 1.25). The model diagnosis reveals that the residuals were randomly distributed with no significant auto-correlation. The results of this study suggest that PDL models may be better than SARIMA models (R-square increased and RMSE decreased). The findings of this study may facilitate the development of early warning systems for the control and prevention of this widespread disease. Further analyses were conducted using classification trees to identify major mosquito species of Ross River virus (RRV) transmission and explore the threshold of mosquito density for RRV disease in Brisbane, Australia. The results show that Ochlerotatus vigilax (RR: 1.028; 95% CI: 1.001 - 1.057) and Culex annulirostris (RR: 1.013, 95% CI: 1.003 - 1.023) were significantly associated with RRV disease cycles at a lag of 1 month. The presence of RRV was associated with average monthly mosquito density of 72 Ochlerotatus vigilax and 52 Culex annulirostris per light trap. These results may also have applications as a decision support tool in disease control and risk management planning programs. As RRV has significant impact on population health, industry, and tourism, it is important to develop an epidemic forecast system for this disease. The results of this study show the disease surveillance data can be integrated with social, biological and environmental databases. These data can provide additional input into the development of epidemic forecasting models. These attempts may have significant implications in environmental health decision-making and practices, and may help health authorities determine public health priorities more wisely and use resources more effectively and efficiently.

In 1998, the Southern Saltmarsh Mosquito Aedes camptorhynchus (‘Campto’) was accidentally transported from Australia to Hawke’s Bay in New Zealand, from where it dispersed to another 10 localities mainly on the North Island. After an investment of NZ$70 million over 10 years, this saltmarsh carrier of Ross River virus was eradicated in a world-first program which surprised many. How did it get there? How did it spread? How did the team cope when it arrived at Kaipara Harbour, said to be the largest harbour in New Zealand? This book draws together the entire unprecedented campaign, uncovering the twists and turns and nasty surprises the team had to deal with along the way. Written in an approachable way, it also contains new unpublished technical information which will be sought after by professionals.