A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates.

Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs). Monovalent VLPs elicited neutralizing antibody responses and protected mice and nonhuman primates (NHPs) against homologous challenges, but they were not cross-protective. In contrast, NHPs immunized with trivalent VLPs were completely protected against aerosol challenge by each of these three EEVs. Passive transfer of IgG from immunized NHPs protected mice against aerosolized EEV challenge, demonstrating that the mechanism of protection was humoral. Because they are replication incompetent, these trivalent VLPs represent a potentially safe and effective vaccine that can protect against diverse encephalitis viruses.

The ecology and epidemiology of Ross River and Murray Valley encephalitis viruses in Western Australia: examples of One Health in Action.

Arboviruses are maintained and transmitted through an alternating biological cycle in arthropods and vertebrates, with largely incidental disease in humans and animals. As such, they provide excellent examples of One Health, as their health impact is inextricably linked to their vertebrate hosts, their arthropod vectors and the environment. Prevention and control requires a comprehensive understanding of these interactions, and how they may be effectively and safely modified. This review concentrates on human disease due to Ross River and Murray Valley encephalitis viruses, the two major arboviral pathogens in Australia. It describes how their pattern of infection and disease is influenced by natural climatic and weather patterns, and by anthropogenic activities. The latter includes human-mediated environmental manipulations, such as water impoundment infrastructures, human movements and migration, and community and social changes, such as urban spread into mosquito larval habitats. Effective interventions need to be directed at the environmental precursors of risk. This can best be achieved using One Health approaches to improve collaboration and coordination between different disciplines and cross-sectoral jurisdictions in order to develop more holistic mitigation and control procedures, and to address poorly understood ecological issues through multidisciplinary research.

[Counsel for traveling children]. / Conseils pour enfants voyageurs.

Consultation of child traveler has two main objectives: to assess of health risk related to the child's health status and history and also the risk related to travel environment; to counsel and prescribe preventive measure to reduce these travel health risks. The evaluation is based on physical examination and a detailed interview including personal history and information regarding the regions of proposed travel. Up to date knowledge of the epidemiology of visited sites, preventive measures and presumptive treatment is required. Essential health recommendations include, in case of exposure, prevention of malaria, arthropod borned diseases and vaccine preventable diseases. For all destinations advice regarding prevention of diarrhea, accident risks and aggravation of preexisting chronic diseases is needed. Universal primary prevention counselling is valuable for all travellers regardless of their age. In the case of children, special attention must be given to food and water hygiene, sun and heat exposure, swimming risks and transports security measures. Evaluation of risk and health education take time and often several visits are needed to complete the immunization schedule before departure.

Human arboviral encephalitis.

Worldwide, arboviral illnesses constitute the most important international infectious threat to human neurological health and welfare. Before the availability of effective immunizations, approximately 50,000 cases of Japanese encephalitis occurred in the world each year, one-fifth of which cases proved lethal and a much larger number were left with severe neurological handicaps. With global climate change and perhaps other factors, the prevalences of some arboviral illnesses appear to be increasing. Arboviral illnesses, including Japanese encephalitis, tick-borne encephalitis, Yellow fever, and others, are emerging as possible global health care threats because of biological warfare. This chapter will review ecology, pathophysiology, diagnosis, management, and outcome of the forms of arboviral encephalitis that are of greatest importance in North America, together with some of the most important arboviral encephalitides prevalent in other parts of the world.

Murray Valley encephalitis: a review of clinical features, diagnosis and treatment.

Murray Valley encephalitis virus (MVEV) is a mosquito-borne virus that is found across Australia, Papua New Guinea and Irian Jaya. MVEV is endemic to northern Australia and causes occasional outbreaks across south-eastern Australia. 2011 saw a dramatic increase in MVEV activity in endemic regions and the re-emergence of MVEV in south-eastern Australia. This followed significant regional flooding and increased numbers of the main mosquito vector, Culex annulirostris, and was evident from the widespread seroconversion of sentinel chickens, fatalities among horses and several cases in humans, resulting in at least three deaths. The last major outbreak in Australia was in 1974, during which 58 cases were identified and the mortality rate was about 20%. With the potential for a further outbreak of MVEV in the 2011-2012 summer and following autumn, we highlight the importance of this disease, its clinical characteristics and radiological and laboratory features. We present a suspected but unproven case of MVEV infection to illustrate some of the challenges in clinical management. It remains difficult to establish an early diagnosis of MVEV infection, and there is a lack of proven therapeutic options.

[Study on the characteristics of major mosquito-borne infectious diseases in Three Gorges Reservoir Area from 1997 to 2008].

OBJECTIVE: Characteristics and tendency of mosquito and major mosquito-borne diseases (including epidemic encephalitis B and malaria) were analyzed in the Three Gorges Reservoir Area from 1997 to 2008. METHODS: Information on surveillance data related to mosquito-borne infectious diseases and on mosquito density and category, from 1997 to 2008 was collected from Health Surveillance System in Three Gorges Reservoir Area. Data regarding meteorological factors and construction of Three Gorges Reservoir was also collected. Pearson and Poisson models were used. RESULTS: From 1997 to 2008, in the Three Gorges Reservoir Area, the incidence rates of epidemic encephalitis B and malaria were decreasing. Positive correlations were shown between indoor and outdoor mosquito density as well with temperature with coefficient as 0.281 and 0.355 respectively. Correlations of mosquito-borne diseases with indoor and outdoor mosquito density were positive, with correlation coefficient as 0.340 and 0.328 respectively. CONCLUSION: There seemed lack of evidence to prove that negative influences had occurred on the incidence of mosquito-borne infectious diseases or the mosquito density after the Three Gorges Reservoir water storage came into being in 2003, however, long-time surveillance program needs to be carried out to gather information on this issue.

Vaccination for tropical mosquito borne encephalitis.

Tropical mosquito borne encephalitis is an important condition in neurology. This bring public health burden for many countries. An important way to face up these infections is the vaccination. In this article, the author will detail and discuss on vaccination for two important tropical mosquito borne encephalitis, Japanese encephalitis and West Nile virus infection.

[Flavivirus encephalitis].

The member of the genus Flavivirus family Flaviviridae are arthropod-transmitted viruses. This genus includes vector-borne neurotropic viruses such as the tick-borne encephalitis virus serocomplex and the Japanese encephalitis virus serocomplex. Flavivirus encephalitis is the generic term for encephalitis caused by viruses belonging to this genus. The Japanese encephalitis virus is still active in Japan, and the tick-borne encephalitis virus is prevalent in Hokkaido, the northern region of Japan. The West Nile fever/encephalitis epidemic has been active in North and South America since 1999.

Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus.

The Japanese encephalitis virus (JEV) serocomplex, which also includes Murray Valley encephalitis virus (MVEV), is a group of antigenically closely related, mosquito-borne flaviviruses that are responsible for severe encephalitic disease in humans. While vaccines against the prominent members of this serocomplex are available or under development, it is unlikely that they will be produced specifically against those viruses which cause less-frequent disease, such as MVEV. Here we have evaluated the cross-protective values of an inactivated JEV vaccine (JE-VAX) and a live chimeric JEV vaccine (ChimeriVax-JE) against MVEV in two mouse models of flaviviral encephalitis. We show that (i) a three-dose vaccination schedule with JE-VAX provides cross-protective immunity, albeit only partial in the more severe challenge model; (ii) a single dose of ChimeriVax-JE gives complete protection in both challenge models; (iii) the cross-protective immunity elicited with ChimeriVax-JE is durable (>or=5 months) and broad (also giving protection against West Nile virus); (iv) humoral and cellular immunities elicited with ChimeriVax-JE contribute to protection against lethal challenge with MVEV; (v) ChimeriVax-JE remains fully attenuated in immunodeficient mice lacking type I and type II interferon responses; and (vi) immunization with JE-VAX, but not ChimeriVax-JE, can prime heterologous infection enhancement in recipients of vaccination on a low-dose schedule, designed to mimic vaccine failure or waning of vaccine-induced immunity. Our results suggest that the live chimeric JEV vaccine will protect against other viruses belonging to the JEV serocomplex, consistent with the observation of cross-protection following live virus infections.

Vaccination against mosquito borne viral infections: current status.

Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japanese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne diseases such as malaria, dengue infection and West Nile virus infection. In this article, the author reviews the issues on vaccination of some important tropical mosquito borne infectious diseases.

Emergence and virulence of encephalitogenic arboviruses.

Each arbovirus that causes encephalitis is geographically restricted by the availability of appropriate vectors and reservoir hosts. These viruses evolve regionally by recombination, reassortment and point mutation and can "emerge" as causes of human encephalitis through extension to new geographic regions or by selection of more virulent or more efficiently transmitted virus variants. The properties of arboviruses that result in encephalitis involve efficient replication in peripheral tissues after initiation of infection, production of a viremia, entry into the central nervous system and efficient replication in neurons with spread to additional populations of neurons. Many of these steps are determined by properties of the envelope glycoproteins responsible for cellular attachment, but changes in noncoding regions of the genome, as well as in other structural and nonstructural proteins, also contribute to neurovirulence.

Epizootic activity of Murray Valley encephalitis and Kunjin viruses in an aboriginal community in the southeast Kimberley region of Western Australia: results of mosquito fauna and virus isolation studies.

We undertook annual surveys of flavivirus activity in the community of Billiluna in the southeast Kimberley region of Western Australia between 1989 and 2001 [corrected]. Culex annulirostris was the dominant mosquito species, particularly in years of above average rains and flooding. Murray Valley encephalitis (MVE) virus was isolated in 8 of the 13 years of the study from seven mosquito species, but more than 90% of the isolates were from Cx. annulirostris. The results suggest that MVE virus is epizootic in the region, w ith activity only apparent in years with average or above average rainfall and increased numbers of Cx. annulirostris. High levels of MVE virus activity and associated human cases were detected only once (in 1993) during the survey period. Activity of MVE virus could only be partially correlated with wet season rainfall and flooding, suggesting that a number of other factors must also be considered to accurately predict MVE virus activity at such communities.

Vaccines and animal models for arboviral encephalitides.

Arthropod-borne viruses ("arboviruses") cause significant human illness ranging from mild, asymptomatic infection to fatal encephalitis or hemorrhagic fever. The most significant arboviruses causing human illness belong to genera in three viral families, Togaviridae, Flaviviridae, and Bunyaviridae. These viruses represent a significant public health threat to many parts of the world, and, as evidenced by the recent introduction of the West Nile virus (WNV) to the Western Hemisphere, they can no longer be considered specific to any one country or region of the world. Like most viral diseases, there are no specific therapies for the arboviral encephalitides; therefore, effective vaccines remain the front line of defense for these diseases. With this in mind, the development of new, more effective vaccines and the appropriate animal models in which to test them become paramount. In fact, for many important arboviruses (e.g. California serogroup and St. Louis encephalitis viruses), there are currently no approved vaccines available for human use. For others, such as the alphaviruses, human vaccines are available only as Investigational New Drugs, and thus are not in widespread use. On the other hand, safe and effective vaccines against tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus (JEV) have been in use for decades. New challenges in vaccine development have been met with new technologies in vaccine research. Many of the newer vaccines are now being developed by recombinant DNA technology. For example, chimeric virus vaccines have been developed using infectious clone technology for many of the arboviruses including, WNV, JEV, and TBEV. Other successful approaches have involved the use of naked DNA encoding and subsequently expressing the desired protective epitopes. Naked DNA vaccines have been used for TBEV and JEV and are currently under development for use against WNV. The development of less expensive, more authentic animal models to evaluate new vaccines against arboviral diseases will become increasingly important as these new approaches in vaccine research are realized. This article reviews the current status of vaccines, both approved for use and those in developmental stages, against the major arboviral encephalitides causing human disease. In addition, research on animal models, both past and present, for these diseases are discussed.

Zooprophylaxis or zoopotentiation: the outcome of introducing animals on vector transmission is highly dependent on the mosquito mortality while searching.

BACKGROUND: Zooprophylaxis, the diversion of disease carrying insects from humans to animals, may reduce transmission of diseases such as malaria. However, as the number of animals increases, improved availability of blood meals may increase mosquito survival, thereby countering the impact of diverting feeds. METHODS: Computer simulation was used to examine the effects of animals on the transmission of human diseases by mosquitoes. Three scenarios were modelled: (1) endemic transmission, where the animals cannot be infected, eg. malaria; (2) epidemic transmission, where the animals cannot be infected but humans remain susceptible, e.g. malaria; (3) epidemic disease, where both humans and animals can be infected, but develop sterile immunity, eg. Japanese encephalitis B. For each, the passive impact of animals as well as the use of animals as bait to attract mosquitoes to insecticide was examined. The computer programmes are available from the author. A teaching model accompanies this article. RESULTS: For endemic and epidemic malaria with significant searching-associated vector mortality, changing animal numbers and accessibility had little impact. Changing the accessibility of the humans had a much greater effect. For diseases with an animal amplification cycle, the most critical factor was the proximity of the animals to the mosquito breeding sites. CONCLUSION: Estimates of searching-associated vector mortality are essential before the effects of changing animal husbandry practices can be predicted. With realistic values of searching-associated vector mortality rates, zooprophylaxis may be ineffective. However, use of animals as bait to attract mosquitoes to insecticide is predicted to be a promising strategy.

Sentinel Chicken Surveillance Program in Australia, July 2002 to June 2003.

Detection of flavivirus seroconversions in sentinel chicken flocks located throughout Australia is used to provide an early warning of increased levels of Murray Valley encephalitis (MVE) and Kunjin (KUN) virus activity in the region. During the 2002-2003 season low levels of flavivirus activity were detected in northern Australia compared to previous years. MVE and KUN virus activity was detected in the Kimberley and Pilbara regions of Western Australia and the Northern Territory but not in north Queensland, New South Wales or Victoria. This is similar to the previous season. There were no reported cases of disease caused by either virus.

Pre-West Nile virus outbreak: perceptions and practices to prevent mosquito bites and viral encephalitis in the United States.

Mosquitoes can transmit over 100 of the viruses that can cause encephalitis, meningitis, and hemorrhagic disease in humans (Chin 2000; Gubler 1996; Monath 1989). While much is known about the ecology, epidemiology, and clinical manifestations of the arboviral encephalitides (Campbell et al. 2002; Centers for Disease Control and Prevention 1997; Gubler 1998; Hayes 1989; Hubálek and Halouzka 1999), little empirical research exists regarding the U.S. population's knowledge of mosquitoes and arboviral encephalitis, particularly prior to the U.S. outbreak of West Nile virus (WNV) in 1999. A nationally representative 55-item survey instrument was successfully administered to 1,500 adults in the United States and an additional 250 adults in six states in the Northeast (Connecticut, Delaware, New Jersey, New York, Pennsylvania, and Rhode Island) regarding mosquitoes and mosquito-borne viral encephalitis. A summary outcome measure for mosquito bite prevention was created. Analyses revealed that the following were statistically significant predictors of behaviors taken to prevent mosquito bites: being concerned about being bitten by mosquitoes, perceived effectiveness of staying indoors in late afternoon and early evening was protective, perceived effectiveness that mosquito repellent is not harmful to health, owning dogs and/or cats as pets, being married, and being > or = 18-44 years old. Being concerned about being bitten by mosquitoes was the most robust predictor of behavioral action to prevent mosquito bites (OR = 7.3; 95% CI = 4.3, 12.2). Observed misperceptions and inadequate knowledge regarding insect repellents suggest increased promotion of the safety and efficacy of DEET-containing insect repellents is warranted.