The Policy Research Programme, Department of Health, UK.

We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

Defining the causal relationship between a microbe and encephalitis is complex. Over 100 different infectious agents may cause encephalitis, often as one of the rarer manifestations of infection. The gold-standard techniques to detect causative infectious agents in encephalitis in life depend on the study of brain biopsy material; however, in most cases this is not possible. We present the UK perspective on aetiological case definitions for acute encephalitis and extend them to include immune-mediated causes. Expert opinion was primarily used and was supplemented by literature-based methods. Wide usage of these definitions will facilitate comparison between studies and result in a better understanding of the causes of this devastating condition. They provide a framework for regular review and updating as the knowledge base increases both clinically and through improvements in diagnostic methods. The importance of new and emerging pathogens as causes of encephalitis can be assessed against the principles laid out here.

Encephalitis means inflammation of the brain matter. Despite being a rare condition, encephalitis is of public health importance worldwide because it has high morbidity and mortality. Yet, many details about its epidemiology have yet to be elucidated. This review attempts to summarise what is known about the epidemiology of the infective causes of encephalitis and is based on a literature search of the Medline archives. Infection is the most common cause identified, with viruses being the most important known aetiological agents. Incidence varies between studies but is generally between 3.5 and 7.4 per 100,000 patient-years. Encephalitis affects peoples of all ages; however, incidence is higher in the paediatric population. Although both sexes are affected, most studies have shown a slight predominance in males. Encephalitis occurs worldwide; some aetiologies have a global distribution (herpesviruses) while others are geographically restricted (arboviruses). Although definite epidemiological trends are evident, it is difficult to make generalisations as few population-based studies exist, most cases are not reported to health authorities, and many possible pathogens are implicated but in most cases a cause is never found. A better understanding of the epidemiology of this devastating disease will pave the way for better prevention and control strategies.

Our findings support the hypothesis that new and emerging infectious agents, or new forms of immune-mediated encephalitis, may be responsible for cases currently of unknown cause and encourage the ongoing global effort to identify these. Our review highlights research areas that might lead to a better understanding of the causes of encephalitis and ultimately reduce the morbidity and mortality associated with this devastating condition.