Dalla Lana School of Public Health

A comprehensive study of the causes and outcomes of encephalitis in England has become one of the top 10 most cited papers in the Lancet Infectious Diseases. The study was conducted by England’s Health Protection Agency, but the Chief Investigator, Natasha Crowcroft, led the study for the most part from Canada in her role as Chief of Infectious Diseases at Public Health Ontario and Associate Professor at Laboratory Medicine and Pathobiology and the Dalla Lana School of Public Health, University of Toronto.

Encephalitis is a rare, but often deadly, inflammation of the brain. A person may develop changes in mental state, such as confusion or drowsiness, a loss of consciousness, seizures, or a lapse into coma. The most common known cause of encephalitis is infection by a virus, such as the herpes simplex virus. But, in many cases, a cause is never found, which makes it difficult to devise new treatments or develop interventions to prevent serious complications. Around 700 people in England develop acute encephalitis every year and about 7% of these cases are fatal.

Over 200 patients with encephalitis were studied in this, the largest study of its kind in England. A cause was found for 63% of cases; the most frequent was herpes simplex virus (19%). However, because of the many unknown causes among the cases of encephalitis (37%), the authors uncovered the potential for hidden yet-to-be discovered infectious diseases.

Prompt distinction between causes of acute encephalitis is essential to ensure appropriate care. The recommended treatment for most cases of encephalitis is an antiviral called acyclovir, which is effective in treating encephalitis cases caused by the herpes virus. However, this is of no help for patients with antibody-related encephalitis (8%), for whom immunosuppressive treatment can be effective when started early. One priority for clinicians that has emerged is to consider antibody-mediated encephalitis so that the correct diagnosis is made and treatment is provided. It is hoped these findings will help clinicians to diagnose and treat patients as early as possible.

Vaccination has substantially reduced the number of encephalitis cases associated with vaccine-preventable diseases. Some vaccines may very rarely cause encephalitis and it is reassuring that no cases were identified in this study.

This important study has led to the production of UK national clinical case definitions for encephalitis and better laboratory methods and algorithms for identifying causes of this devastating syndrome. It has demonstrated a model approach and methodology for the detection of emerging infections. The overall approach was designed to provide a platform for future studies including, for example, an evaluation of the burden of disease, the long-term impact on quality of life, and a study of neuroimaging and outcome. It has led to an ongoing partnership between UK and Canadian researchers. It has also triggered interest from multi-disciplinary experts from around the world with an interest in encephalitis, benefitting patients worldwide.