Geographic Variation of Notified Ross River Virus Infections in Queensland, Australia, 1985-1996

The spatial and temporal variations of Ross River virus infections reported in Queensland, Australia, between 1985 and 1996 were studied by using the Geographic Information System. The notified cases of Ross River virus infection came from 489 localities between 1985 and 1988, 805 between 1989 and 1992, and 1,157 between 1993 and 1996 (chi2(df = 2) = 680.9; P < 0.001). There was a marked increase in the number of localities where the cases were reported by 65 percent for the period of 1989-1992 and 137 percent for 1993-1996, compared with that for 1985-1988. The geographic distribution of the notified Ross River virus cases has expanded in Queensland over recent years. As Ross River virus disease has impacted considerably on tourism and industry, as well as on residents of affected areas, more research is required to explore the causes of the geographic expansion of the notified Ross River virus infections.

Exploratory spatial analysis of social and environmental factors associated with the incidence of Ross River Virus in Brisbane, Australia

We used geographic information systems and a spatial analysis approach to explore the pattern of Ross River virus (RRV) incidence in Brisbane, Australia. Climate, vegetation and socioeconomic data in 2001 were obtained from the Australian Bureau of Meteorology, the Brisbane City Council and the Australian Bureau of Statistics, respectively. Information on the RRV cases was obtained from the Queensland Department of Health. Spatial and multiple negative binomial regression models were used to identify the socioeconomic and environmental determinants of RRV transmission. The results show that RRV activity was primarily concentrated in the northeastern, northwestern, and southeastern regions in Brisbane. Multiple negative binomial regression models showed that the spatial pattern of RRV disease in Brisbane seemed to be determined by a combination of local ecologic, socioeconomic, and environmental factors.

Difference in mosquito species (Diptera: Culicidae) and the transmission of Ross River Virus between coastline and inland areas in Brisbane, Australia

This study examined the distribution of major mosquito species and their roles in the transmission of Ross River virus (RRV) infection for coastline and inland areas in Brisbane, Australia (27°28′ S, 153°2′ E). We obtained data on the monthly counts of RRV cases in Brisbane between November 1998 and December 2001 by statistical local areas from the Queensland Department of Health and the monthly mosquito abundance from the Brisbane City Council. Correlation analysis was used to assess the pairwise relationships between mosquito density and the incidence of RRV disease. This study showed that the mosquito abundance of Aedes vigilax (Skuse), Culex annulirostris (Skuse), and Aedes vittiger (Skuse) were significantly associated with the monthly incidence of RRV in the coastline area, whereas Aedes vigilax, Culex annulirostris, and Aedes notoscriptus (Skuse) were significantly associated with the monthly incidence of RRV in the inland area. The results of the classification and regression tree (CART) analysis show that both occurrence and incidence of RRV were influenced by interactions between species in both coastal and inland regions. We found that there was an 89% chance for an occurrence of RRV if the abundance of Ae. vigifax was between 64 and 90 in the coastline region. There was an 80% chance for an occurrence of RRV if the density of Cx. annulirostris was between 53 and 74 in the inland area. The results of this study may have applications as a decision support tool in planning disease control of RRV and other mosquito-borne diseases.

Bayesian spatiotemporal analysis of socio-ecologic drivers of Ross River Virus transmission in Queensland, Australia

This study aims to examine the impact of socio-ecologic factors on the transmission of Ross River virus (RRV) infection and to identify areas prone to social and ecologic-driven epidemics in Queensland, Australia. We used a Bayesian spatiotemporal conditional autoregressive model to quantify the relationship between monthly variation of RRV incidence and socio-ecologic factors and to determine spatiotemporal patterns. Our results show that the average increase in monthly RRV incidence was 2.4% (95% credible interval (CrI): 0.1–4.5%) and 2.0% (95% CrI: 1.6–2.3%) for a 1°C increase in monthly average maximum temperature and a 10 mm increase in monthly average rainfall, respectively. A significant spatiotemporal variation and interactive effect between temperature and rainfall on RRV incidence were found. No association between Socio-economic Index for Areas (SEIFA) and RRV was observed. The transmission of RRV in Queensland, Australia appeared to be primarily driven by ecologic variables rather than social factors.

Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Ross River virus (RRV) is a mosquito-borne member of the genus Alphavirus that causes epidemic polyarthritis in humans, costing the Australian health system at least US$10 million annually. Recent progress in RRV vaccine development requires accurate assessment of RRV genetic diversity and evolution, particularly as they may affect the utility of future vaccination. In this study, we provide novel RRV genome sequences and investigate the evolutionary dynamics of RRV from time-structured E2 gene datasets. Our analysis indicates that, although RRV evolves at a similar rate to other alphaviruses (mean evolutionary rate of approx. 8x10(-4) nucleotide substitutions per site year(-1)), the relative genetic diversity of RRV has been continuously low through time, possibly as a result of purifying selection imposed by replication in a wide range of natural host and vector species. Together, these findings suggest that vaccination against RRV is unlikely to result in the rapid antigenic evolution that could compromise the future efficacy of current RRV vaccines.

Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection

Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

Ross River virus evolution : implications for vaccine development

Ross River virus is a mosquito-borne alphavirus that causes approximately 5000 cases of epidemic polyarthritis in Australia each year and has direct medical-associated costs of approximately US$15 million annually. While mosquito control programs are able, at best, to contain rather than prevent this disease, natural infection with Ross River virus confers lifelong protection against subsequent clinical infection. A killed-virus vaccine has been developed, which is in Phase III clinical trials. Analyses of intra-host genetic diversity and of long-term evolutionary changes in Ross River virus populations suggest that antigenic variation is unlikely to pose a threat to the efficacy of this vaccine.

Ross River virus arthritis

“Epidemics” of a benign disease causing polyarthralgia and rash were first described in Australia in 1927.63 Following the recovery of the causative agent and the advent of serologic tests able to diagnose Ross River virus infection, epidemic polyarthritis has been recognized as endemic in Australia and has occurred as epidemics in numerous Pacific nations. Approximately 4000 cases of epidemic polyarthritis are reported in Australia each year, with a peak of 7800 cases in 1996. Some confusion has been generated recently by use of the term Ross River fever to describe clinical Ross River virus infections because fever does not develop in more than half of those with clinical disease.59 Additional confusion has been generated by efforts to describe any polyarthritis caused by an Australian arbovirus as epidemic polyarthritis. The term epidemic polyarthritis should be used to describe only clinical disease caused by Ross River virus.