**7. Prognosis**

Prognosis depends on the particular type of arbovirus causing disease, and on the age and prior health status of the patient. The prognosis is worse in very young patients, elderly pa‐ tients, and patients with compromised immune systems. LAC encephalitis most often oc‐ curs in children, while WNV and SLV encephalitis usually occur in persons older than 50 years of age [20]. Encephalitis caused by EEV and JEV carries a high risk for serious neuro‐ logical damage and death. Death rates range all the way up to 20% for arboviral encephali‐ tis, and the rates of lifelong effects due to brain damage can reach 60% for some types of arboviruses.

## **8. Vaccine prevention for arboviral infections**

Infection with an arbovirus provides immunity to that specific virus, but not to other arbovi‐ ruses, suggesting that arboviral infection is a vaccine preventable disease. Thus, the devel‐ opment of new, more effective vaccines and the appropriate animal models in which to test them are paramount. Although for many important arboviruses, there are currently no ap‐ proved vaccines available for human use, while for some, safe and effective vaccines have been used for decades. For instance, a clinical approved inactivated vaccine against TBEV has been used in Russia, Germany, Austria, and China [93].

JEV is one of the few arboviruses for which a vaccine is available. The JEV vaccine made from infected mouse brain can achieve efficacies of at least 80% [94]. But because of the cost and safety concerns, development of a better JEV vaccine has been an ongoing project. For example, the development of a live-attenuated virus vaccine (SA14-14-2, for use in China and a part of Asia) and more recently, in March 2009, the FDA approved a new, inactivated cell-culture-derived JEV vaccine (IXIARO) for use in adult travelers over the age of 17 [95-98]. In addition, a live-attenuated yellow fever–Japanese encephalitis chimeric vaccine (IMOJEV™) was recently licensed in Australia and is under review in Thailand [98].

As for WNV, an approved and efficacious vaccine for humans is not available, even though equine WNV vaccines are in use [99]. However, it is anticipated that a WNV vaccine for hu‐ man use will be available within a couple of years. In addition, inactivated TBEV vaccine is currently available in Europe [100].

For others, such as the Alphaviruses, human vaccines are available only as Investigational New Drugs, and thus are not in widespread use.The rest of the arboviral vaccines are cur‐ rently undergoing clinical phase III trials, and are anticipated to be available for public us‐ age within 5 years if everything goes as planned. While some of these vaccines have currently only received approval for animal usage, newer versions for human use are in the process of being evaluated or developed.

New challenges in vaccine development have been met with new technologies in vaccine re‐ search. Many of the newer vaccines are now being developed by recombinant DNA technol‐ ogy [100]. For example, chimeric virus vaccines have been developed using infectious clone technology for many arboviruses including, WNV, JEV, and TBEV. Other successful ap‐ proaches 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 be‐ come increasingly important as these new approaches in vaccine research are realized.

However, technical issues do exist in the nature of these viruses. One of the unique biologi‐ cal features in a majority of arboviruses is the constitution of the genetic material. The posi‐ tive-sense single-stranded RNA genome can function as mRNA, which is capable of producing an infectious virus if the RNA is inside a biologically functional identity. To add the second layer of difficulty in vaccine development, arboviruses may have multiple life cy‐ cles, since the physical morphology of these virions may be a mosaic form *in vivo* [62]. These features may be one of the reasons why developing a vaccine against arboviruses is such a difficult task. Despite the potential dilemma, there are some successes; though continued improvement in developing arboviral vaccines that are capable of preventing encephalitis is an urgently needed and challenging task.

Other foreseeable methods for areas where arboviral encephalitis is prevalent include insec‐ ticide spraying, which may be used to control outbreaks. Wearing insect repellent and avoiding outdoor activities when mosquitoes are active may also be helpful.
