Pseudorabies virus encephalitis in humans: a case series study.

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine.

Human encephalitis caused by pseudorabies virus infection: a case report.

Pseudorabies virus (PRV) primarily infects swine but can infect cattle, dogs, and cats. Several studies have reported that PRV can cross the specie barrier and induce human encephalitis, but a definitive diagnosis of human PRV encephalitis is debatable due to the lack of PRV DNA detection. Here, we report a case of human PRV encephalitis diagnosed by the next-generation sequencing (NGS) of PRV sequences in the cerebrospinal fluid (CSF) of a patient. A male pork vendor developed fever and seizures for 6 days. NGS results showed PRV sequences in his CSF and blood. Sanger sequencing showed that PRV DNA in the CSF and PRV antibodies in both the CSF and blood were positive. MRI results revealed multiple inflammatory lesions in the bilateral hemisphere. Based on the clinical and laboratory data, we diagnosed the patient with PRV encephalitis. This case suggests that PRV can infect humans, causing severe viral encephalitis. People at risk of PRV infection should improve their self-protection awareness.

Dynamic cerebrospinal fluid analyses of severe pseudorabies encephalitis.

We reported a severe human pseudorabies encephalitis case and described a dynamic clinical manifestation with cerebrospinal fluid analyses and cytological and serological evaluation, which may elucidate the mechanism of PRV infection and facilitate clinical diagnosis and treatment in human.

Aujeszky's disease (pseudorabies) virus detection in cerebrospinal fluid in experimentally infected pigs.

The presence of Aujeszky's disease virus in cerebrospinal fluid of experimentally infected pigs was studied using the techniques of virus isolation and PCR. Pigs, some of which were previously vaccinated against Aujeszky's disease, were inoculated with different doses of the Aujeszky's disease NIA-3 strain. At the time of death or sacrifice, a sample of cerebrospinal fluid was taken and tested for the presence of virus using the mentioned techniques. Virus was isolated only from one sample, while it was detected by PCR in most of them. The higher sensitivity of the PCR technique and the possible presence of antiviral antibodies in the cerebrospinal fluid are reasons that can be argued to explain this fact. By PCR, the virus was detected more efficiently when digested cerebrospinal fluid cells were used as DNA source than when using whole cerebrospinal fluid, suggesting that the virus could be cell-associated. Aujeszky's disease virus could not be detected by PCR in pigs which survived the acute phase of the infection and were euthanased at 8 weeks post-inoculation, when they were latently infected. This indicated that the cerebrospinal fluid is not an adequate sample for the diagnosis of latency. Since Aujeszky's disease virus was detected from most of the tested samples, we believe that this could be an adequate procedure for the quick diagnosis of Aujeszky's disease.

Neuropathogenesis of pseudorabies: leakage of anti-viral antibody and serum constituents into cerebrospinal fluid of infected pigs.

Antibody levels to pseudorabies virus (PRV) in cerebrospinal fluid (CSF) were compared to serum levels from immunized and infected pigs. Antibody was measured by single-dilution indirect solid-phase radioimmunoassay (IRIA). There was significantly higher CSF anti-PRV IgG relative to serum anti-PRV IgG (anti-PRV index, %) from infected pigs (1.390%, n = 14) than from vaccinated ones (0.141-0.149%, n = 5 and 7). The index from vaccinated and challenged pigs was intermediate (0.627%, n = 16), suggesting that vaccination cannot abrogate but can reduce the severity of encephalitis. Piglets with maternal antibody contained minimal CSF antibody similar to that of vaccinated animals. The CSF anti-PRV antibody was detected in piglets infected with as low as 10(2) TCID50 at 15 days postinfection. In infected pigs, the elevated CSF anti-PRV level was due to a leakage of serum antibody through a possible blood-brain barrier (BBB) impairment but not due to intrathecal antibody synthesis. Multiple regression analysis showed that the leakage was more time dependent than dose dependent. Leakage was detected until at least 4 weeks after disappearance of acute clinical symptoms. We have associated different levels of CSF anti-viral antibody with various infection or vaccination conditions.