UC Berkeley

Acute encephalitis syndrome (AES) is a disease condition characterized be presence of fever, and altered consciousness with or without presence of seizures or a neurological deficit. This definition is broad, and AES may be caused by a wide variety of neurotropic viruses, bacteria, protozoa, fungi or may even be non-infectious in etiology. Most AES is however considered to be due to a viral encephalitis, a condition which is common in many developing countries. The epidemiologic features of AES, especially in adults are still not well defined, and this study is first of its kind from India.

This dissertation consists of three original studies and two systematic literature reviews. We first performed a retrospective chart review of all patients with fever presenting to a single hospital in central India, to determine proportions of patients with AES, and to understand diagnostic and management practices in this condition. We found that AES accounts for about 20% of all acute fevers, has a high mortality, remains frequently undiagnosed, and is mostly empirically treated as malaria. In the subsequent year we designed a descriptive study to understand the temporal and spatial profile, and survival characterictics. We also conducted a case-control study to understand risk factors for AES. We found that most AES occurs in hot and humid months of the year, and proximity to a river or stream may be associated with development of the disease. About half of all patients with AES died within 30 days of disease, and low Glasgow coma score, and need for assisted ventilation significantly predicted hazard for mortality. In our extensive laboratory testing of cerebrospinal fluid and serum samples obtained from 152 AES cases suspected of having viral encephalitis, we found 31 (17%) patients who had a confirmed viral etiology. Enteroviruses were the commonest etiology (9.2% of all AES cases) followed by flaviviruses (4.3% of all AES cases). Based on serology 16 (8.8%) patients had probable leptospirosis. In a third of all cases etiology remained unknown. Low socioeconomic status was the only risk factor significantly associated with AES. These studies have provided novel insights into epidemiology of AES in India, and it is likely that most adult AES is due to water borne enteroviruses rather than vector borne flaviviruses as previously believed