Michael D. A. Lindsay

Arboviruses causing human disease in the Australasian zoogeographic region

SummaryOver 65 arboviruses have been reported from countries in the Australasian zoogeographic region, but only a few have been implicated in human disease. These include the flaviviruses Murray Valley encephalitis (MVE), Kunjin (KUN), Kokobera (KOK), and dengue, particularly types 1 and 2; the alphaviruses Ross River (RR), Barmah Forest (BF), and Sindbis (SIN); and the bunyaviruses, Gan Gan and Trubanaman. In this paper recent epidemiological and clinical results pertaining to these viruses are reviewed, with major emphasis on MVE and RR viruses. The extensive early studies of Australian arboviruses have been reviewed by Doherty [49, 50], and their ecology and vectors more recently by Kay and Standfast [87]. In addition, the biology of MVE and KUN [113] and RR [87, 114] viruses have been the subjects of more detailed reviews.The Australasian zoogeographic region is defined as countries east of the Wallace and Weber lines, two hypothetical lines in the Indo-Australian archipelago where the fauna of the Australasian and Oriental regions meet. Seroepidemiological studies of human arboviral infections have suggested that the Japanese encephalitis flavivirus and the chikungunya alphavirus occur only in the Oriental region, whereas the related MVE and RR viruses, respectively, are restricted to the Australasian region [85, 148]. Serological results from Wallacea, the zone between the Wallace and Weber lines, are not so clear-cut [85]. This review is therefore restricted to countries east of Wallacea, specifically New Guinea and Australia.

Discovery of a Widespread Infestation of Aedes albopictus in the Torres Strait, Australia

ABSTRACT Aedes albopictus is a container-breeding Stegomyia mosquito that has dispersed widely from its origins in Southeast Asia. Because Ae. albopictus is a known dengue vector and a potential vector of a variety of arboviruses and it can tolerate cooler climates than Aedes aegypti, Australian quarantine and health authorities have strategies to detect and eliminate it from international ports. Following the detection of 42 adult Ae. albopictus in BG-Sentinel traps set on Yorke island in the Torres Strait of Australia in April 2005, extensive surveys were conducted to determine the distribution of Ae. albopictus in the Torres Strait and adjoining Cape York Peninsula. A total of 17 islands and the northern peninsula area of Cape York Peninsula were surveyed by collection of larvae and pupae from flooded containers and human bait collections of adult mosquitoes with aspirators and sweep nets. Aedes albopictus was detected on 10 islands and comprised 100% of the day-biting container-breeding mosquitoes on Yorke and Stephens Islands. No Ae. albopictus were detected in the mainland sites on Cape York. Retrospective genetic analysis of larvae collected in April 2004 and April 2005 on Yorke Island indicated that Ae. albopictus was present in low densities in 2004 and that there were 3 genetically distinct mitochondrial haplotypes on Yorke Island in April 2005. Additionally, on Yorke Island there is evidence that Ae. albopictus is displacing Aedes scutellaris.

Identification of australian arboviruses in inoculated cell cultures using monoclonal antibodies in ELISA

Summary An ELISA using a panel of specific monoclonal antibodies was developed to identify all alpha and flaviviruses isolated from mosquitoes caught throughout Australia. This technique is sensitive and rapid and is more specific than the traditional methods used to identify flaviviruses. The ability to identify unknown virus isolates from field‐caught mosquitoes quickly and accurately improves the efficiency of arbovirus surveillance programs and allows health authorities to give an early warning of an increased health risk from a mosquito‐borne virus in a particular region.Abbreviations: BF, Barmah Forest; CPE, cytopathic effect; Mab, monoclonal antibody; MVE, Murray Valley encephalitis; RR, Ross River.

The changing epidemiology of Murray Valley encephalitis in Australia: the 2011 outbreak and a review of the literature.

Murray Valley encephalitis virus (MVEV) is the most serious of the endemic arboviruses in Australia. It was responsible for six known large outbreaks of encephalitis in south-eastern Australia in the 1900s, with the last comprising 58 cases in 1974. Since then MVEV clinical cases have been largely confined to the western and central parts of northern Australia. In 2011, high-level MVEV activity occurred in south-eastern Australia for the first time since 1974, accompanied by unusually heavy seasonal MVEV activity in northern Australia. This resulted in 17 confirmed cases of MVEV disease across Australia. Record wet season rainfall was recorded in many areas of Australia in the summer and autumn of 2011. This was associated with significant flooding and increased numbers of the mosquito vector and subsequent MVEV activity. This paper documents the outbreak and adds to our knowledge about disease outcomes, epidemiology of disease and the link between the MVEV activity and environmental factors. Clinical and demographic information from the 17 reported cases was obtained. Cases or family members were interviewed about their activities and location during the incubation period. In contrast to outbreaks prior to 2000, the majority of cases were non-Aboriginal adults, and almost half (40%) of the cases acquired MVEV outside their area of residence. All but two cases occurred in areas of known MVEV activity. This outbreak continues to reflect a change in the demographic pattern of human cases of encephalitic MVEV over the last 20 years. In northern Australia, this is associated with the increasing numbers of non-Aboriginal workers and tourists living and travelling in endemic and epidemic areas, and also identifies an association with activities that lead to high mosquito exposure. This outbreak demonstrates that there is an ongoing risk of MVEV encephalitis to the heavily populated areas of south-eastern Australia.

Emergence of Barmah Forest virus in Western Australia.

To the editor: Barmah Forest (BF) virus is a mosquito-borne alphavirus, found only in Australia, which causes outbreaks of polyarthritis in humans. The disease is very similar to epidemic polyarthritis caused by infection with Ross River virus, another Australian alphavirus. BF virus was first isolated from mosquitoes in the State of Western Australia in 1989. After this, small clusters of human cases were diagnosed in the arid northern and central regions of Western Australia in 1992, and the first substantial outbreak of human disease due to infection with BF virus (BF virus disease) occurred in the southwestern region of the state during the spring and summer (September-March) of 1993-94 (2). No evidence of BF virus activity had been found in these regions before these events, which suggests that the virus had only recently been introduced to Western Australia. This report describes the timing and distribution of BF virus disease in humans and the isolation of the virus from mosquitoes in Western Australia, which corroborate the view that BF virus is an emerging virus in this state. The ecology of Australian arboviruses that cause human disease, including BF virus, has recently been reviewed (3). BF virus was first isolated from Culex annulirostris mosquitoes collected at the Barmah Forest in northern Victoria (southeastern Australia) in 1974 (4). It was first shown to infect humans in New South Wales (central-eastern and southeastern Australia) in 1986 (5) and was reported as a cause of clinical disease in humans in 1988 (6). The most common clinical features include polyarthritis, arthralgia, myalgia, fever, rash, and lethargy (7); in some cases, symptoms may persist for more than 6 months (2). Although the symptoms are similar to those caused by infection with Ross River virus, there is little cross-reaction between the two viruses in serologic tests (8), and differentiating between infections caused by either is generally not difficult. The first true outbreak of BF virus disease occurred concurrently with an outbreak of Ross River virus infection at Nhulunbuy in the Northern Territory in early 1992 (9). The principal vectors of BF are believed to be mosquitoes, and although the vertebrate hosts of BF virus are not known, serologic surveys in eastern Australia have suggested that marsupials are involved in the natural cycle. BF virus was first detected in Western Australia in 1989. Since then, 73 isolates of the virus have been obtained from mosquitoes trapped in several different regions of Western Australia (Table 1). The first human cases of BF virus disease in Western Australia were reported in 1992, and 67 serologically confirmed cases have now been diagnosed. The locations of towns where human cases have occurred or where mosquitoes that yielded BF virus were collected are shown in Figure 1. Eight isolates of the virus were obtained from five different mosquito species (Table 1) collected at Billiluna, a small, remote aboriginal community in an arid area in the southeastern Kimberley region in April 1989 (10). The infected mosquitoes were collected 3 weeks after heavy local rains. Only moderate wet season rains were recorded in the remainder of the Kimberley region, and no cases of BF virus disease were reported from any region in Western Australia that year. There have been no subsequent isolations of BF virus from mosquitoes collected at Billiluna, despite annual collections in the region. No human cases have been reported from Billiluna. The first cases of BF virus disease in Western Australian were reported almost 3 years later, either individually or in small clusters from towns in the arid East Kimberley, Pilbara, Gascoyne, Murchison and Southeast (Goldfields) regions between April and September (Autumn-Spring) 1992. Most activity was reported from the towns of Exmouth (six cases) and Carnarvon (four cases). All of these cases occurred during or just after much larger outbreaks of disease caused by Ross River virus. This suggested that BF and Ross River viruses may have similar mosquito vectors and require similar environmental conditions for successful transmission. The main environmental factor contributing to the 1992 outbreaks of Ross River virus disease was extremely heavy rain in these normally arid regions during autumn and winter (11). BF virus was isolated from five species of mosquito in the Fortescue region of the Pilbara and from three species in the West Gascoyne, just prior to, and during, these arid-region outbreaks. In coastal regions of the Pilbara, the main vector of BF virus appears to be Aedes vigilax, a salt marsh-breeding species. Large numbers of this species develop after very high tides or heavy rains on salt marshes. It is also the main vector of Ross River virus in these regions (12). Several other temporary freshwater ground pool-breeding species in the subgenus Ochlerotatus, particularly Ae. eidsvoldensis and Ae. EN Marks’ species #85, were found to be infected with the virus in inland areas or coastal areas where such pools develop. These preliminary investiga1 This report is adapted from and expands on a previous bulletin. (1) Dispatches

First reported case of transfusion-transmitted Ross River virus infection

PathWest Laboratory Medicine WA detected RRV IgM antibodies using an inhouse indirect immunofluorescence antibody (IFA) test, but no RRV antibodies were detected using an inhouse haemagglutination inhibition (HI) antibody test 10 days after blood donation. RRV IgM antibodies are detected by IFA testing within a few days of onset of illness and routinely persist for several weeks or, occasionally, months or years. IFA tests are less prone to false-positive results compared with enzyme immunoassays. The HI antibody test primarily detects IgG antibodies, which appear within several weeks but after the IgM response.

Molecular epidemiology and evolution of mosquito-borne flaviviruses and alphaviruses enzootic in Australia

Three distinct patterns in the molecular epidemiology and evolution are evident among the alphaviruses and flaviviruses enzootic in Australia. One pattern, exemplified by MVE and KUN viruses, is of a single genetic type evolving slowly and uniformly in geographically widely separated regions of Australia with no evidence of independent divergence. The second pattern, exemplified by RR virus, is of separate genotypes evolving in different geographic regions with significant nucleotide divergence between genotypes. The third pattern, exemplified by SIN virus, is of a succession of temporally related genotypes that extend over most of the Australian continent, with relatively low levels of nucleotide divergence within a genotype, and which are each replaced by the subsequent genotype. These patterns are associated in part due to the nature and dispersal of their vertebrate hosts. Nucleotide divergence rates for Australian alphaviruses are similar to those reported elsewhere. Genomic relationships between Australian flavivirus members of the JE virus serological complex and between Australian alphaviruses are discussed, and evidence is presented for a possible new genomic lineage of SIN virus.

Investigation of the southern limits of Murray Valley encephalitis activity in Western Australia during the 2000 wet season.

Western Australia experienced its worst-ever outbreak of the mosquito-borne Murray Valley encephalitis (MVE) virus during the 2000 wet season. Highest-on-record rainfall throughout much of the state during the 2000 wet season gave rise to extensive mosquito breeding and increased MVE virus transmission, resulting in nine cases of encephalitis. Activity of MVE virus in Western Australia is monitored by detecting MVE virus-specific antibodies in serum from sentinel chickens, located at towns and communities throughout the north of the state. However, during 2000, all 28 flocks of chickens seroconverted to MVE virus, including a flock located >600 km further south than MVE virus activity had ever previously been recorded. Furthermore, the majority of the nine cases of encephalitis occurred outside the enzootic Kimberley region. We therefore undertook a major serosurvey of domestic chicken flocks both south and east of the previously defined regions of virus activity. The results suggest that MVE virus activity extended as far south as the Midwest and northern Goldfields during 2000. A new southern limit of activity of MVE virus is therefore proposed. The results have implications for managing outbreaks of MVE virus in Western Australia and have enabled us to locate additional sentinel flocks as part of the MVE surveillance program for future years.

The Effect of Climate on the Incidence of Vector-Borne Viral Diseases in Australia: The Potential Value of Seasonal Forecasting

Over 80 vector-borne viruses have been described in Australia, although relatively few have been associated with clinical disease in humans or domestic animals. These viruses are classified as arboviruses (an abbreviation of arthropod-borne viruses), and by defmition are transmitted between blood-feeding arthropod vectors (mosquitoes, biting midges and ticks) and vertebrate hosts, undergoing cycles of replication in both hosts alternately. The major viral diseases of humans are mosquito-borne and include Ross River and Barmah Forest viruses, both members of the Alphavirus genus of the family Togaviridae; and Murray Valley encephalitis, Kunjin, Japanese encephalitis, and dengue viruses of the Flavivirus genus of the family Flaviviridae. The major viral diseases of livestock are transmitted by biting midges (Culicoides sp.) and include bovine ephemeral fever virus, a member of the Ephemerovirus genus of the family Rhabdoviridae; bluetongue viruses of the Orbivirus genus of the family Reoviridae; and Akabane virus, a member of the Simbu group in the Bunyavirus genus of the family Bunyaviridae.

Prevalence of neutralising antibodies to Barmah Forest, Sindbis and Trubanaman viruses in animals and humans in the south-west of Western Australia

A study was undertaken in the south-west of Western Australia to investigate potential vertebrate hosts of Barmah Forest virus (BFV), Sindbis virus (SINV) and Trubanaman virus (TRUV) following isolation of these viruses from mosquitoes collected during routine surveillance for arboviruses. Over 3000 animal and human sera collected between 1979 and 1995 were tested for the presence of neutralising antibodies to each of the viruses. The overall prevalence of antibodies to BFV, SINV and TRUV was 0.4%, 0.3% and 1.6%, respectively. Antibodies to BFV were detected only in quokkas (3.2%), horses (1.2%) and humans (0.9%). No definitive evidence of infection with BFV was detected in samples collected prior to 1992, supporting previous suggestions that BFV was introduced into the region after this time. Antibodies to SINV were detected in western native cats (16.7%), emus (4.5%), rabbits (0.8%) and horses (0.7%), and evidence of TRUV infection was most common in western grey kangaroos (21.1%), feral pigs (3.6%), rabbits (2.4%), foxes (2.3%), quokkas (1.6%) and horses (1.6%).