**14. Treatment, prevention and control**

shown good specificity in the diagnosis of JEV in both blood and CSF samples but it has poor sensitivity as the virus is often cleared from the peripheral circulation/CSF by the time the test is performed. With the advent of monoclonal antibodies as potential diag‐ nostic tool (Chávez *et al.,* 2010), the rapid detection of JE antigen in cerebrospinal fluid has become possible. The different diagnostic tests have been given in Table 2. However, the most rapid and potential diagnostic tool for JE diagnosis have been shown to be MAC-ELISA (Robinson *et al.,* 2010) and indirect fluorescent antibody. MRI of the brain can also be used in diagnosis. MRI changes can be co-related (Misra *et al.,* 2011) with the

Immunization against JE is cost effective strategy for control and prevention of JE. It has been reported globally that there is a decrease in incidence rates of JE in endemic areas which are administered with high immunization. The 3 most important types of JE vac‐ cines, administered in current era are: the mouse brain derived, purified, inactivated vac‐ cine based on either the Nakayama or Beijing strains of the JE virus; the cell culture derived inactivated JE vaccine based on the viral Beijing P3 strain and the cell culture derived live attenuated JE vaccine based on the SA 14‐14‐2 strain of the JE virus. In JEV infection, the immunity against prM, E and NS1 proteins is more effective than that of other viral proteins in host defense. (Gao et al., 2010). Currently available vaccines against JE include chemically inactivated vaccines (INV) and a live attenuated vaccine (LAV). Although a mouse brain derived INV produced by BIKEN had been the only in‐ ternationally approved vaccine and has been used worldwide since the 1960s. But it had a drawback as there were reports of severe adverse events including acute disseminated encephalomyelitis (ADEM) in people vaccinated with it. In early 2009, Vero cell derived INVs produced by Intercell (Austria) and BIKEN (Japan) were licensed. Although these INVs are useful in developed markets, INVs are not ideally suited for nationwide vacci‐ nation programs for many endemic countries, since INVs require multiple doses to in‐ duce long lasting immunity. LAVs are thus a useful alternative and have been used for decades in China, and other Asian countries, but their substrate and the production methods have still not been approved in other markets, which serve as a drawback to this vaccine. (Ishikawa et al., 2011). Live-attenuated virus vaccines (LAVs) and inactivat‐ ed virus vaccines (INVs) serve against flaviviral disease, they are potent and economical but do not suit immunocompromised patients. INVs are safer, but are more expensive to produce and less potent. Hence there is an immense need of devicing new and im‐

Type I IFNs are critical for controlling pathogenic virus infections and can enhance immune responses. Hence their impact on the effectiveness of live-attenuated vaccines involves a bal‐ ance between limiting viral antigen expression and enhancing the development of adaptive immune responses. The influence of type I IFNs on these parameters has been examined fol‐ lowing immunization with RepliVAX WN, a single-cycle flavivirus vaccine (SCFV). Repli‐

type of encephalitis and duration of illness.

172 Encephalitis

**13. Vaccines: Immunization against JE**

proved products.

There is no specific treatment or anti-viral agent for JEV infection, it is proving to be a per‐ sistent threat. Monoclonal antibodies (Yamanaka et al., 2010), corticosteroids, interferonα-2a or ribavirin were not that effective in clinical outcome. The effect of rosamarinic acid (RA) has been shown as an effective anti-viral agent that reduces JE viral load along with proin‐ flammatory cytokines in experimental animal. Neutrophils have been also shown to have degradative effect on JEV. Usage of anti-sense molecules (vivo-morpholino) directed against the viral genome, in combating the virus through inhibiting viral replication has been dem‐ onstrated (Nazmi et al., 2010). Mycophenolic acid (Sebastian et al., 2011) inhibits JE virus by inhibiting its replication.

**15. Conclusion and future implications**

sense of urgency is required to address this matter.

, Sneham Tiwari1

1 Centre for Cellular and Molecular Biology (CCMB−CSIR), Uppal, India

College of Medicine, Florida International University, Miami, USA

**Acknowledgements**

**Author details**

Lucknow, India

Shailendra K. Saxena1

Madhavan P. N. Nair3

Viral encephalitis has proved to be a huge disaster globally, which has engulfed several lives and has shattered various economies. It has been a hot topic amongst the researchers today globally and various ways necessary to combat against the virus are on the way. In‐ tense research for the knowabouts of the virus is carried in several countries, devising strat‐ egies to fight with the virus. As a result of severe efforts, JE has been virtually eliminated in most of the countries after the immunization with inactivated mouse brain-derived vaccine, during last four decades. Because of absence of treatment strategies personal protection is the only apt way to reduce disease incidence. Mosquito control is the sole available preven‐ tive measure for JEV transmission. Research on JEV needs to be initiated at much wider scale, which should include development of effective anti-viral agents and vaccine strat‐ egies. Immunization is needed in JE prone areas. Over use of the vaccines should be avoided otherwise the virus might develop resistance against drugs which are administered fre‐ quently. Quarantine checks should be done at international immigration and emigration points, to keep a check on the spread of virus via foreign travelers. Vector control program should be designed in a way that they can control the risk of vectors in an efficient way. General awareness camps should be organized in rural areas to spread alertness in the local population and confronting them with hygiene management and preventive measures. Sys‐ tematic and combinatorial approach with the joint efforts of scientists, molecular biologists, doctors, drug developers, policy makers and local population is the need of hour. A high

Japanese Encephalitis Virus: The Complex Biology of an Emerging Pathogen

http://dx.doi.org/10.5772/54111

175

Authors are grateful to Dr Ch. Mohan Rao, Director, Centre for Cellular and Molecular Biol‐ ogy (Council of Scientific and Industrial Research, India), for the encouragement and sup‐ port for this work. NIH Awards (R37DA025576; R01MH085259) support S.K.S. and M.P.N.

, Rakhi Saxena1

2 Department of General Pathology & Microbiology, Saraswati Medical & Dental College,

3 Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim

, Asha Mathur2

and

Prevention methods are very important for minimizing JE infection (Saxena *et al.,* 2008). Childhood immunization is done by using inactivated mouse brain-derived vaccine which is based on either the Nakayama or Beijing strains of the JE virus, the cell culture derived, inactivated JE vaccine based on the Beijing P-3 strain ; and the cell cultures derived, live – attenuated vaccine based on the SA 14-14-2 strain (Halstead *et al.,* 2011) of the JE virus. Re‐ combinant poxvirus vectors expressing the E and NS1 proteins of the JEV boosting a good immune response in mice models can be used as a vaccine. The prevention of vector –man contact is very good preventive method this can be done by eliminating potential mosquito breeding areas, environmental sanitation, waste water management by treating the water with larvicide either by *Gambusa* (larva-eating fish), drying and wetting of rice fields, fre‐ quent vaccination should be implemented, and as well as personal protective measures. Re‐ ports have shown that induction of nitric oxide synthase plays a protective role against JEV (Saxena *et al*., 2001). Diethyldithiocarbamate has been also experimentally shown to inhibit JEV infection. Future predictions of the disease and drug designing can be enhanced by computer aided design databases, which can design *in silico* the most efficient drugs which can be tested experimentally and then can be clinically tried. For the development of appro‐ priate and effective therapy there is an immediate need to understand host factors role in JEV –induced neuropathogenesis (Gupta *et al.,* 2011). Effective anti-viral drugs have yet to be found. Medicines are given mainly to relieve symptoms. Vaccination for people at risk, eliminate mosquito breeding grounds, improve drainage, maintain clean piggeries, use in‐ sect repellent and mosquito nets are some of the preventive measures which should be com‐ monly undertaken.

The strategy for prevention and control of JE should include major components such as awareness among general public on the prevention and control of the disease, vector control and immunization. Environmental control is also one important factor as it has been studied that there is a positive impact of urbanization and economic development in the reduction of JE transmission, as clean and sanitized economies will not support environment necessa‐ ry for mosquito breeding. Land areas under cultivation with impact of agrochemicals may work for reduction of vector density. Along with good environmental strategies vector con‐ trol is also an important aspect. Maintenance of low vector densities is the need of hour.

Spraying, larviciding and aerial application are the method used for reduction of vector den‐ sities. However, alternatives to aerial application like spraying/fogging/Ultra Low Volume (ULV) application are also under consideration. Along with this long term i.e. non‐chemical vector control such as water management is also helpful. Use of agrochemicals to control pests may have had indirect effect on vector control. Also, use of larvivorous fish may also be applicable in permanent water bodies. Personal protection is very important as vectors can feed on humans in outdoors, hence over vegetation and shaded humid places should be bit ignored. Minimizing outdoor activity for reducing the exposure time to mosquitoes and wearing long sleeved clothes are some habits needed to be undertaken consideration along with public information and awareness.
