In a high-risk population, the rHEV vaccine was effective in the prevention of hepatitis E. (ClinicalTrials.gov number, NCT00287469 [ClinicalTrials.gov].).
Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, beta-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation.
Viremia, fecal shedding and antibody responses to hepatitis E virus (HEV) infections are poorly understood. To better characterize HEV infections, these responses were examined in 67 patients with acute markers for hepatitis E who were admitted to the Infectious Disease Hospital in Kathmandu, Nepal in 1993. A single stool and multiple sera from each patient were examined using polymerase chain reaction to detect HEV RNA. Sera were also examined for antibodies to HEV. Viremia, fecal shedding, and IgM and IgG to HEV were detected in 93%, 70%, 79%, and 87% of 67 patients, respectively. Viremia or fecal shedding (or both) were detected in 14 patients from whom IgM and IgG to HEV were not detected. Viremia lasted at least 2 weeks in nearly all subjects and at least 39 days in 1 subject. Our results suggest that viremia is a common occurrence in patients infected with HEV.
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