John S. Mackenzie

Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses

Mosquito-borne flaviviruses provide some of the most important examples of emerging and resurging diseases of global significance. Here, we describe three of them: the resurgence of dengue in tropical and subtropical areas of the world, and the spread and establishment of Japanese encephalitis and West Nile viruses in new habitats and environments. These three examples also illustrate the complexity of the various factors that contribute to their emergence, resurgence and spread. Whereas some of these factors are natural, such as bird migration, most are due to human activities, such as changes in land use, water impoundments and transportation, which result in changed epidemiological patterns. The three examples also show the ease with which mosquito-borne viruses can spread to and colonize new areas, and the need for continued international surveillance and improved public health infrastructure to meet future emerging disease threats.

Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus.

Since it was first described in Australia in 1994, Hendra virus (HeV) has caused two outbreaks of fatal disease in horses and humans, and an isolated fatal horse case. Our preliminary studies revealed a high prevalence of neutralizing antibodies to HeV in bats of the genus PTEROPUS:, but it was unclear whether this was due to infection with HeV or a related virus. We developed the hypothesis that HeV excretion from bats might be related to the birthing process and we targeted the reproductive tract for virus isolation. Three virus isolates were obtained from the uterine fluid and a pool of foetal lung and liver from one grey-headed flying-fox (Pteropus poliocephalus), and from the foetal lung of one black flying-fox (P. alecto). Antigenically, these isolates appeared to be closely related to HeV, returning positive results on immunofluorescent antibody staining and constant-serum varying-virus neutralization tests. Using an HeV-specific oligonucleotide primer pair, genomic sequences of the isolates were amplified. Sequencing of 200 nucleotides in the matrix gene identified that these three isolates were identical to HeV. Isolations were confirmed after RNA extracted from original material was positive for HeV RNA when screened on an HeV Taqman assay. The isolation of HeV from pteropid bats corroborates our earlier serological and epidemiological evidence that they are a natural reservoir host of the virus.

Ecology and Geographical Expansion of Japanese Encephalitis Virus

Japanese encephalitis virus (JEV) (Flavivirus: Flaviviridae) is a leading cause of encephalitis in eastern and southern Asia. The virus is maintained in a zoonotic cycle between ardeid wading birds and/or pigs and Culex mosquitoes. The primary mosquito vector of JEV is Culex tritaeniorhynchus, although species such as Cx. gelidus, Cx. fuscocephala, and Cx. annulirostris are important secondary or regional vectors. Control of JEV is achieved through human and/or swine vaccination, changes in animal husbandry, mosquito control, or a combination of these strategies. This review outlines the ecology of JEV and examines the recent expansion of its geographical range, before assessing its ability to emerge in new regions, using the hypothetical establishment in the United States as a case study.

The natural history of Hendra and Nipah viruses

Pteropid bats (flying foxes), species of which are the probable natural host of both Hendra and Nipah viruses, occur in overlapping populations from India to Australia. Ecological changes associated with land use and with animal husbandry practices appear most likely to be associated with the emergence of these two agents.

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.

Genetic analysis of West Nile New York 1999 encephalitis virus

Analysis of the genome of the flavivirus responsible for the 1999 New York City encephalitis epidemic cloned from human brain by reverse-transcription polymerase chain reaction Indicates its identity as a lineage I West Nile virus (WNV; WNV-NY1999) closely related to WNVs previously isolated In the Middle East.

The zoonotic flaviviruses of Southern, South-Eastern and Eastern Asia, and Australasia: the potential for emergent viruses.

The genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south‐eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick‐borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito‐borne, six are tick‐borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya‐Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread.

Japanese encephalitis as an emerging virus: the emergence and spread of Japanese encephalitis virus in Australasia.

Japanese encephalitis (JE) virus has a great propensity to spread, expanding its range through much of southeastern Asia in the past four decades (Umenai et al. 1985; Burke and Leake 1988; Vaughn and Hoke 1992; Monath and Heinz 1996). In the 1990s, JE spread into southern Pakistan (Igarashi et al. 1994) and to Haryana State (Prasad et al. 1993) and Kerala State (Dhanda et al. 1997) in northwestern and southwestern India, respectively. In the east, JE has invaded the eastern Indonesian archipelago, New Guinea, and the Torres Strait of northern Australia (Hanna et al. 1996b; Mackenzie et al. 1997a). The eastward spread of JE from the Oriental to the Australasian zoogeographic region and the threat this poses to the Pacific is the focus of this chapter. It is also interesting to note that there are also certain parallels in the emergence of JE in the Australasian region with the recent emergence of West Nile (WN) virus in North America, and particularly the emergence of the two viruses in novel zoogeographic regions.

Immunodominant epitopes on the NS1 protein of MVE and KUN viruses serve as targets for a blocking ELISA to detect virus-specific antibodies in sentinel animal serum

Two mosquito-borne flaviviruses, Murray Valley encephalitis (MVE) and Kunjin (KUN), are the aetiological agents of Australian encephalitis. MVE causes a severe and potentially fatal form of the disease while KUN is responsible for only a few relatively mild cases. Therefore it is important that serological tests used in flavivirus surveillance differentiate between infections with these two viruses. However, this has been hampered in the past by the close antigenic relationships between flaviviruses in traditional serological assays. An epitope blocking ELISA using MVE-specific and KUN-specific monoclonal antibodies (mAb) reacting to the non-structural protein NS1 of these viruses and a flavivirus group-specific mAb reacting to the envelope (E) protein was assessed for testing sentinel animals for seroconversion to specific flavivirus infections. Using these assays we were able to detect serum antibodies to a variety of flavivirus in laboratory infected rabbits, and naturally infected chickens and in the case of primary infections, differentiate those caused by KUN or MVE. These assays are now used routinely in our laboratory for testing chicken sera from sentinel flocks in the Kimberley and Pilbara regions of north Western Australia.

Climate change and dengue: a critical and systematic review of quantitative modelling approaches

BackgroundMany studies have found associations between climatic conditions and dengue transmission. However, there is a debate about the future impacts of climate change on dengue transmission. This paper reviewed epidemiological evidence on the relationship between climate and dengue with a focus on quantitative methods for assessing the potential impacts of climate change on global dengue transmission.MethodsA literature search was conducted in October 2012, using the electronic databases PubMed, Scopus, ScienceDirect, ProQuest, and Web of Science. The search focused on peer-reviewed journal articles published in English from January 1991 through October 2012.ResultsSixteen studies met the inclusion criteria and most studies showed that the transmission of dengue is highly sensitive to climatic conditions, especially temperature, rainfall and relative humidity. Studies on the potential impacts of climate change on dengue indicate increased climatic suitability for transmission and an expansion of the geographic regions at risk during this century. A variety of quantitative modelling approaches were used in the studies. Several key methodological issues and current knowledge gaps were identified through this review.ConclusionsIt is important to assemble spatio-temporal patterns of dengue transmission compatible with long-term data on climate and other socio-ecological changes and this would advance projections of dengue risks associated with climate change.