oa Editorial [Hot Topic: The Challenge of Viral Encephalitis: From Etiological Diagnosis to Efficient Antiviral Drug Discovery (Guest Editor: Laurent Dacheux)]

Human encephalitis is a complex neurological syndrome constituting a challenging public health problem. This severe disease, defined as the combination of an inflammation of the brain parenchyma and neurological dysfunction, is associated with high rates of mortality and morbidity. Several causes of encephalitis have been identified, but infectious agents remain the most common. These agents include various microorganisms, with viruses the most frequently implicated. Over the last two decades, several studies have provided insight into the overall clinical, epidemiological and etiological picture of viral encephalitis, but our knowledge remains far from complete. The incidence of the main viral etiological agents of encephalitis, including herpesviruses (herpes simplex viruses and varicella zoster virus in particular), enteroviruses, several arboviruses and nonarthropod-borne viral zoonotic pathogens, such as the rabies and nipah viruses, has been determined. However, the inventory of viruses responsible for encephalitis is not exhaustive, with gaps depending on the strategy or standardized procedures used for virus identification and the tools available for diagnosis. A high proportion of acute encephatitis cases remain of unknown etiology and it seems likely that other viruses are responsible for these cases. Moreover, this inventory is not fixed and it should be updated based on geographic, socioeconomic, public health or even climatic considerations (particularly for arboviruses). This need for change is exemplified by the introduction of an unprecedented number of encephalitic viruses, which have emerged or spread worldwide over the last decade, particularly in the Southeast Asian and Western Pacific regions. The treatment strategies for patients suffering from viral encephalitis remain extremely limited. Indeed, other than for herpesviruses (more precisely, herpes simplex viruses), no drug has yet been clearly demonstrated to be efficient, with validated activity against a broad range of the viral agents of encephalitis identified to date. The management of patients is based principally on symptomatic treatment. There is therefore a great need for research in this field, and current efforts are focused on the development of novel antiviral drugs, with the prospect of rapidly delivering effective treatments for this devastating syndrome. In this context, the special topic of Infectious Disorders - Drug Targets in this issue is viral encephalitis, and attempts have been made to cover very different and complementary aspects of the field. An up-to-date overview of several diagnosis tools for virus identification, focusing in particular on the most recent advances, presented by K. Mutton and M. Guiver, in “Laboratory Techniques for Human Viral Encephalitis Diagnosis”. A selection of five major viruses causing encephalitis in humans is then presented, each starting from the specific biological background of the virus and moving on to the various molecular targets and antiviral drugs that have been tested to date, are available or in development. We begin with herpes simplex viruses, presented by F. Rozenberg, C. Deback and H. Agut in their review “Herpes simplex encephalitis: from virus to therapy”. These viruses are among the most common causes of viral encephalitis in humans, but they also provide an example of the successful development and use of an effective antiviral drug, in the form of acyclovir. The next two viruses presented are the rabies and Japanese encephalitis viruses. Rabies is a deadly reemerging virus and Japanese encephalitis virus is an emerging agent. Effective prophylactic vaccination exists for both these viruses, but they nonetheless continue to cause high rates of death, particularly in developing countries, and no active antiviral drugs are available. The state-of-the art concerning potential new strategies for the prevention and cure of infections caused by rabies virus is reviewed by L. Dacheux, O. Delmas and H. Bourhy in their article entitled Human “Rabies Encephalitis Prevention and Treatment: Progress Since Pasteur's Discovery”. Dutta K., A. Nazmi and A. Basu present a complete review of recent advances in our knowledge of Japanese encephalitis virus and antiviral drug development in “Chemotherapy in Japanese encephalitis: are we there yet?”. Finally, two examples of challenging antiviral drug developments for two other major emerging viruses responsible for encephalitis are presente. The first of these two examples is henipaviruses, reviewed by F. Vigant and B. Lee in their article “Hendra and nipah infection: pathology, models and potential therapies”. The final example is provided by enteroviruses, presented by T.C. Chen and S.R. Shih, in their review entitled “Drug Discovery in Enteroviral Infections”. I am convinced that the high quality and relevance of each of these state-of-the-art reviews will ensure that they of considerable interest to the scientific community working in the field of viral encephalitis in humans, and also to the larger community of scientists involved in the challenging enterprise of developing innovative new antiviral drugs....