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Japanese encephalitis among hospitalized pediatric and adult patients with acute encephalitis syndrome in Hanoi, Vietnam 1995.

The etiologic spectrum of acute encephalitis syndrome (AES) has not been well defined in Vietnam. Cohort and case-control studies were performed on all adult and pediatric AES patients admitted to the Neurology Service of Bach Mai Hospital between June 5 and August 3, 1995. Among pediatric AES patients, 31 (67%) of 46 had acute Japanese encephalitis (JE), compared with only two (6%) of 33 adult AES patients (P < 0.0001). For confirmed JE cases, serum specimens obtained 15-21 days after symptom onset had the highest mean anti-JE IgM signal-to-noise (P/N) ratios (8.08 + 1.09 SE). A serosurvey of adult household members did not reveal any cases of recent subclinical JE infection, although 26% had evidence of past JE infection. The use of bed netting was nearly universal but did not appear to reduce the risk of AES or JE. Given the high incidence of JE, particularly among children, Vietnam seems well suited for the development of a targeted JE vaccination strategy.

Acute Disease↗

Powassan virus encephalitis resembling herpes simplex encephalitis.

A boy from New York traveling in Nova Scotia had olfactory hallucinations and other signs of temporal lobe involvement, leading to a diagnosis of herpes simplex encephalitis. The patient was treated with vidarabine and made a complete recovery. However, hemagglutination inhibition, complement fixation, and neutralization tests identified Powassan virus (POW) as the pathogen. Shortly before his trip to Nova Scotia, the patient had traveled in an area where POW encephalitis had occurred in humans (the eastern part of the state of New York), and he also came in contact with a known reservoir of POW infection (a groundhog) at home.

Child↗

Comparison of chickens and pheasants as sentinels for eastern equine encephalitis and St. Louis encephalitis viruses in Florida.

Pheasants and chickens were compared as sentinels for monitoring the transmission of arboviruses of public health significance in Florida during 1991-93. Results suggest that pheasants are better sentinels for eastern equine encephalitis (EEE) virus. They detected virus transmission 3-6 weeks earlier in epizootic years, 2-4 times more frequently during the season, and twice as many birds within a flock seroconverted during a given week. Pheasants detected virus transmission at 2 sites during 2 interepizootic years when chickens failed. Although pheasants detected St. Louis encephalitis (SLE) virus activity somewhat later than did chickens, they had greater seroconversion rates than did chickens. Although both bird species can be used to monitor EEE and SLE viruses, pheasants are more sensitive than chickens as sentinels for EEE virus and as sensitive as chickens as sentinels for SLE virus.

Animals↗

Circulation of eastern equine encephalitis, western equine encephalitis, Ilhéus, Maguari and Tacaiuma viruses in equines of the Brazilian Pantanal, South America.

Neutralizing antibodies to EEE (6.7%), WEE (1.2%), ILH (26.6%), MAG (28.2%) and TCM (15.7%) viruses were found in sera of 432 equines of the Brazilian Pantanal, area where undiagnosed horse deaths are frequently observed. A 4-fold rise in CF titer to EEE virus was detected in acute and convalescent sera of an encephalitis horse sacrificed in 1992. Antibodies to EEE, ILH, MAG and TCM viruses were detected in horses less than 2 years old indicating recent circulation of these viruses in the Pantanal. The evidence of recent equine encephalitis associated with rising CF titer to EEE warrants a more intensive study with attempts to isolate virus from horses with clinical manifestations of encephalitis.

Animals↗

Infection of a poikilothermic cell line (XL-2) with eastern equine encephalitis and western equine encephalitis viruses.

Eastern Equine Encephalitis (EEE) was in Cuba before the 1940s; the virus has been isolated from horses, birds, and rodents during epizootic as well as interepizootic periods. The only isolation of Western Equine Encephalitis (WEE) virus was from a sick pigeon found in the vicinity of Havana University. Both viruses can cause human disease; the isolation of WEE virus from the centre of an urban area emphasises the need for the prompt isolation and rapid identification of these agents. The object of this work was to compare the sensitivity of a continuous cell line (XL-2) from the toad, Xenopus laevis, with primary chick embryo cell cultures (CEC) routinely used for isolation as well as assay of these viruses. Both cell systems were infected with EEE virus isolated from horse brain and WEE virus isolated from a sick pigeon. A clear cytopathic effect (CPE) consisting of rounding and detachment of cells was observed in both cell cultures infected with the two viruses. By 18 hours post-infection, there was partial destruction of the cell monolayer and by 24 hours the CPE was total. The infectious titre of EEE and WEE viruses in XL-2 and CEC were similar. Both viruses produced small plaques (0.5-1.0 mm diameter) in XL-2 cells. Studies on the sensitivity of the XL-2 cells for direct isolation of the two viruses from field samples and for the detection of Cuban flaviviruses by the immunofluorescence test are in progress.

Alphavirus↗

Immunogenicity, genetic stability, and protective efficacy of a recombinant, chimeric yellow fever-Japanese encephalitis virus (ChimeriVax-JE) as a live, attenuated vaccine candidate against Japanese encephalitis.

Yellow fever (YF) 17D vaccine virus, having a 60-year history of safe and effective use, is an ideal vector to deliver heterologous genes from other medically important flaviviruses. A chimeric YF/Japanese encephalitis (JE) virus (ChimeriVax-JE virus) was constructed by insertion of the premembrane and envelope (prME) genes of an attenuated human vaccine strain (SA14-14-2) of Japanese encephalitis (JE) virus between core and nonstructural (NS) genes of a YF 17D infectious clone. The virus grew to high titers in cell cultures and was not neurovirulent for 3- to 4-week-old mice at doses </=6 log10 plaque forming units (pfu) inoculated by the intracerebral (IC) route. In contrast, commercial YF 17D vaccine was highly neurovirulent for weanling mice by the same route. Mice inoculated subcutaneously with one dose of >/=10(3) pfu of ChimeriVax-JE virus were solidly protected against intraperitoneal challenge with a virulent JE virus. Genetic stability of the chimera was assessed by sequential passages in cell cultures or in mouse brain. All attenuating residues and the avirulent phenotype were preserved after 18 passages in cell cultures or 6 passages in mouse brains.

Animals↗

Induction of alternatively spliced spermidine/spermine N1-acetyltransferase mRNA in the human kidney cells infected by venezuelan equine encephalitis and tick-borne encephalitis viruses.

293 and RH cells derived from human embryo kidney were infected by Venezuelan equine encephalitis and tick-borne encephalitis viruses and cDNA libraries representing cellular mRNAs induced or suppressed due to the infection were prepared using suppressive subtractive hybridization. Among the up-regulated clones the RT-PCR and Northern analyses revealed an unusual transcript of the spermidine/spermine N1-acetyltransferase (SSAT) gene that was shown to be an alternatively spliced form containing an additional 110-bp exon. The alternatively spliced transcript is polyadenylated and can be expected to yield only a truncated 71 amino acid polypeptide. This first evidence of the host gene alternatively spliced mRNA induction by RNA viruses raises the questions of its biological role, regulation mechanisms of alternative splicing, and significance for the virus life cycle.

Acetyltransferases↗

Tick-borne encephalitis--a European health challenge. Conference report of the 8th meeting of the International Scientific Working Group on Tick-borne Encephalitis (ISW TBE).

The annual 2006 meeting of the International Scientific Working Group on Tick-borne Encephalitis (ISW TBE) raised the topic "Tick-borne Encephalitis--a European Health Challenge". TBE incidence has more or less increased in all European countries with a TBE risk in the last years (excepting Austria). Additionally, TBE has become an international public health problem because of increasing mobility of people travelling to risk areas. TBE vaccination should be recommended when people travel to endemic regions and come into contact with nature, regardless of the duration of the stay. As no clear recommendations for travellers exist, it will be one of the major future challenges of the ISW TBE to increase problem awareness outside endemic regions and create general recommendations, which are valid for at least all European countries.

Austria↗

Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.

OBJECTIVE: To describe a case of limbic encephalitis which initially presented as viral limbic encephalitis and during the clinical evaluation a renal carcinoma was diagnosed. CASE REPORT: Patient with history of peripheral paresis of right facial nerve, 1 month after symptoms appearance and treatment, developed fever, vomiting, grand mal seizure, decreased level of consciousness, confusion, hallucinations and agitation. The patient initially presented a clinical picture of viral LE. which confirmed by CSF. MRI brain showed areas with pathological intensity signal in the region of limbic system unilateral. During the clinical evaluation a renal carcinoma was discovered and a nephrectomy has been performed. CONCLUSIONS: Although PLE typically presents as a chronic or subacute disease, it may be fulminant and clinically indistinguishable from an acute HSVE. This association pose the problem of a possible relation between this two syndromes and the correct diagnosis is very important, because there are effective treatments.

Acute Disease↗

A synthetic peptide based on the NS1 non-structural protein of tick-borne encephalitis virus induces a protective immune response against fatal encephalitis in an experimental animal model.

Linear immunogenic peptides corresponding to amino acid sequences from the NS1 non-structural protein from tick-borne encephalitis virus (strain Sophyin) were predicted using established algorithms and synthesized. Of the 12 peptides predicted, 11 were able to induce peptide-specific antibodies in BALB/c mice but only 1 of these 11 was able to induce antibodies, which reacted with the native protein in a radio-immune precipitation assay. This peptide corresponds to amino acids 37--55, and forms one of the predicted structurally conserved alpha helices of the virus NS1 protein. It was able to protect 60% of animals against lethal challenge with the homologous highly pathogenic tick-borne encephalitis virus strain, and adoptive transfer experiments indicated the involvement of the antibodies induced by this peptide in its protective activity in mice.

Amino Acid Sequence↗

Pharmacokinetics of human tick-borne encephalitis virus antibody levels after injection with human tick-borne encephalitis immunoglobulin, solvent/detergent treated, FSME-BULIN S/D in healthy volunteers.

This study assessed tick-borne encephalitis virus (TBEV) neutralizing antibody levels after injection of FSME-BULIN S/D (human tick-borne encephalitis immunoglobulin; 0.2 ml/kg body weight) in healthy volunteers. After screening of 18 volunteers for TBEV antibody titers, 12 healthy volunteers with TBEV antibody titers < 5 were entered into the pharmacokinetic part of the study. TBEV antibody titers were analyzed before injection and after 24 h, 48 h, 3 d, 4 d and 8 d. Vital signs, adverse events and laboratory tests for safety were analyzed after intramuscular injection with the immunoglobulin at 4 sites in the gluteal muscles. Injection with 0.2 ml/kg of FSME-BULIN S/D induced a fast increase in, and sustained titers of, neutralizing antibody levels against TBEV. The injections were well tolerated and the safety profile of the product was fully acceptable.

Adult↗

Transmission patterns of St. Louis encephalitis and eastern equine encephalitis viruses in Florida: 1978-1993.

Sentinel chickens were maintained at field sites in 40 Florida counties for varying periods between 1978 and 1993. For each county, the total number of St. Louis encephalitis virus (SLE) or eastern equine encephalitis (EEE) virus seroconversions were divided by the number of chickens exposed to calculate a mean annual seroconversion rate. These rates were used to evaluate the annual and geographical distributions of these viruses within Florida. For SLE, the rates in counties that reported human SLE cases during a widespread epidemic in 1990 were compared with adjusted mean annual seroconversion rates calculated by excluding the epidemic year seroconversion data. In general, actual rates were higher than adjusted rates in counties where human SLE cases were reported in 1990. Similar calculations were made for EEE virus that was unusually abundant in northern Florida during the spring and summer of 1991. In general, EEE virus was distributed in the panhandle and northern regions and SLE virus in the central and southern regions of the state. However, this distribution was not exclusive, and during years of high transmission, either virus can extend beyond its normal range. The annual distribution of SLE and EEE viruses was sporadic, ranging from years with little detectable activity to years with widespread, high-level transmission.

Animals↗

Chimeric Japanese encephalitis virus/dengue 2 virus infectious clone: biological properties, immunogenicity and protection against dengue encephalitis in mice.

A molecular clone of Japanese encephalitis virus (JE virus) was derived from the JE virus Nakayama strain and used to produce infectious JE virus in cell culture. The engineered JE virus resembled the parental JE virus in cell-culture properties and was related closely to other JE virus strains based on nucleotide sequence analysis. The JE virus clone was used as a genetic background for construction of a chimeric virus containing the structural proteins prM and E of Dengue virus, serotype 2. The chimeric JE/dengue 2 virus generated authentic dengue 2 structural proteins as assessed by immunoassays for the dengue E protein. It exhibited a small plaque size and less efficient growth in various cell lines than the parental JE virus. JE/dengue 2 virus was non-neuroinvasive for young adult mice, but displayed partial neurovirulence at doses up to 4 log p.f.u. given intracerebrally. Immunization of 3-week-old mice with JE/dengue 2 virus yielded neutralizing-antibody titres against dengue 2 virus and conferred protection against dengue encephalitis caused by neuroadapted dengue 2 virus. A rise in post-challenge neutralizing-antibody titres against dengue 2 virus in surviving mice suggests that immunization is associated with establishment of a memory antibody response in this model. This study demonstrates the capacity of JE virus to serve as a vector for expression of heterologous flavivirus structural proteins. Similar to previous studies with other chimeric flaviviruses, this approach may be useful as a genetic system for engineering experimental vaccines against Dengue virus and other medically important flaviviruses.

Animals↗

Detection of west Nile and Japanese encephalitis viral genome sequences in cerebrospinal fluid from acute encephalitis cases in Karachi, Pakistan.

Reverse transcriptase-polymerase chain reaction (RT-PCR) on 24 cerebrospinal fluid (CSF) specimens collected between February and August 1992 detected genome sequence of West Nile (WN) virus in 8 specimens and Japanese encephalitis (JE) virus in a single specimen. The results, combined with the data by IgM-ELISA on CSF indicated that a significant proportion of acute encephalitis cases in Karachi, Pakistan, were caused by WN virus infection, while JE virus caused a small fraction.

Acute Disease↗

Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge.

Naked DNA vaccines expressing the prM and E genes of two tick-borne flaviviruses, Russian spring summer encephalitis (RSSE) virus and Central European encephalitis (CEE) virus were evaluated in mice. The vaccines were administered by particle bombardment of DNA-coated gold beads by Accell gene gun inoculation. Two immunizations of 0.5 to 1 microg of RSSE or CEE constructs/dose, delivered at 4-week intervals, elicited cross-reactive antibodies detectable by enzyme-linked immunosorbent assay and high-titer neutralizing antibodies to CEE virus. Cross-challenge experiments demonstrated that either vaccine induced protective immunity to homologous or heterologous RSSE or CEE virus challenge. The absence of antibody titer increases after challenge and the presence of antibodies to E and prM, but not NS1, both before and after challenge suggest that the vaccines prevented productive replication of the challenge virus. One vaccination with 0.5 microg of CEE virus DNA provided protective immunity for at least 2 months, and two vaccinations protected mice from challenge with CEE virus for at least 6 months.

Animals↗

Prevalence of antibodies to tickborne encephalitis and West Nile flaviviruses and the clinical signs of tickborne encephalitis in dogs in the Czech Republic.

Blood sera from 151 dogs from areas of the Czech Republic endemic for human tickborne encephalitis (TBE) were examined for the presence of antibodies to TBE and West Nile (WN) flaviviruses by the haemagglutination-inhibition test Antibodies to TBE virus at titres equal to or exceeding 40 were found in five dogs. Antibodies to WN virus were detected in only one dog that also had a high antibody titre to TBE, suggesting this was a cross-reaction between the two closely related viruses. Three of the dogs (all rottweilers) with a TBE titre of 320 had clinical signs of meningoencephalitis or encephalitis. They all survived after treatment for the clinical signs. It was proved by seroconversion that the disease was caused by the TBE virus in one of these three dogs, and it seems very likely that the virus was responsible for the disease in the other two.

Animals↗

Arbovirus studies in the Guajira region of Venezuela: activities of eastern equine encephalitis and Venezuelan equine encephalitis viruses during an interepizootic period.

Repeated outbreaks of Venezuelan equine encephalitis (VEE) in humans and equines in the Guajira region of Venezuela suggested a sylvatic focus of an epizootic subtype of VEE virus. A surveillance system was established, and virus isolations were attempted from 67,760 mosquitoes as well as sentinel hamsters. Sixteen isolates of eastern equine encephalitis (EEE) and a strain of Itaqui virus were recovered from mosquitoes, and 60 isolates of EEE, two of VEE, and two of Itaqui viruses were recovered from tissues of sentinel hamsters. The VEE virus isolates were shown to be closely related antigenically to prototype VEE ID and the EEE virus isolates were shown to be more closely related to the South American than the North American variety of EEE virus. Evidence for the presence of VEE and EEE viruses in small wild vertebrates was obtained from serologic testing. This study showed, for the first time, the enzootic presence of both VEE ID and EEE viruses during a nonepizoodemic period in the Guajira region.

Alphavirus↗

Isolation of Murray Valley encephalitis virus from the brains of three patients with encephalitis.

Murray Valley encephalitis virus was isolated from the brains of three patients who died from encephalitis during the 1974 epidemic. Isolation of the virus from autopsy material was successful when death occurred within two weeks of the onset of illness; however, no isolations were made from specimens collected before death or from autopsy material obtained from patients who died more than two weeks after the onset of symptoms. The virus was recovered most frequently in embryonated eggs, but two strains were isolated in cell culture.

Adolescent↗