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A case of narcolepsy-cataplexy associated with distemper encephalitis.

Narcolepsy associated with localized brain lesions is described in a 10-month-old Argentine Dogo. Neurological examination and MRI study suggested an inflammatory lesion of the left frontal lobe. Postmortem examination revealed diffuse encephalitis in the forebrain and marked necrotic lesions in the ventral pontine area. Immunohistochemistry for distemper virus antigen showed positive staining of the cytoplasm of many neurones of the pons and cerebral cortex. The pathological pattern was suggestive of post-vaccinal distemper encephalitis and the localization of the lesions was consistent with the neurological syndrome shown by the animal. At any event, the possibility of coincidental findings of distemper encephalitis and idiopathic narcolepsy must be accounted for.

Animals↗

Pleomorphism of fine structure of rabies virus in human and experimental brain.

Identification of the Negri bodies in the brain of an 8-year-old boy who died 8 days after a paralytic illness and 20 days after a dog bite, and who had received 9 injections of Semple's anti-rabies vaccine, provided evidence that he died of acute rabies encephalitis and not of post-vaccinal allergic encephalomyelitis. The Negri bodies in the human subject and those seen in the inoculated mouse differed in their morphological structure: the former consisted of a matrix of very fine granular material bearing larger granules or strands of higher electron-density resembling nucleic acids and representing products of host cell-virus interaction; and the latter showed better defined areas of granular matrix containing tubular, bullet-shaped and elongated forms of viral structures, and nucleocapsids or capsule-deficient cores, representing the virions, emerging from them. Fine structural examination of the patient's brain and of the inoculated mouse has provided evidence of the pleomorphism of the Negri bodies and the various stages of formation of viral material and virions in them, the animal alone showing the mature virions of rabies, and proving the infectivity of the Negri bodies of the human brain.

Animals↗

[Effect of interferon inducers on the development of specific resistance to tick-borne encephalitis].

Various natural and synthetic interferon inducers stimulate postvaccination immunity to tick-borne encephalitis virus in mice. This capacity was found not only in macromolecular synthetic polyribonucleotides such as (poly I)-(poly C), (poly G)-(poly C), (poly A)-(poly U) and substances with much lower molecular weight such as copolymers of vinylpyrrolidone with maleic anhydride, crotonic acid or metacrylic acid but also in a low molecular interferon inducer tiloron. These and other interferon inducers examined (endotoxin S-typhi, statolon) exhibited no parallelism between the intensity of their stimulating effect of immunogenesis and levels of interferon production induced in mice and the associated resistance to tick-borne encephalitis. The results indicate a possibliity of using various interferon inducers for stimulation of post-vaccination immunity to tick-borne encephalitis.

Animals↗

[The clinico-immunological validation of associated immunization].

Clinico-immunological studies on men were conducted using associated immunization by pair combinations of 8 commercial national vaccines (typhoid, plague, typhus, smallpox, tick-borne encephalitis, yellow-fever, cholera and sextaanatoxine). As for reactogenicity and immunological efficiency (serological studies), these pair associations can be subdivided into three main groups. The first group consists of pair combinations of vaccines that cannot exert any influence on immunogenicity of cause the development of frequent post-vaccination reaction or temporary disability (typhus, smallpox, tick-borne encephalitis, yellow-fever vaccines). These preparations are completely compatible in every combination. The second group includes plague and cholera vaccines that reduce its immunogenicity under the influence of more active antigens or increase its reactogenicity being associated with typhoid vaccine or sextaanatoxine. The third group is composed of typhoid vaccine and sextaanatoxine that have high reactogenicity and stable serological shifts. Associations of the first group are the most favourable for anti-epidemiological practice.

Adolescent↗

Plexus neuropathy following vaccination against tick-borne encephalitis and tetanus due to a sports related altered immune state.

A 45-year-old female patient who was practising sports on a competition level, developed a plexus neuropathy subsequent to a vaccination against tick-borne encephalitis (TBE) followed by an inoculation of tetanus toxoid six days later. After the TBE vaccination she continued to exercise intensely until symptoms of a neuritis were noticed. Pronounced endurance exercise has been described to alter the composition and function of the immune system. In our patient a decrease of T-helper cells and a significant lowered CD4/CD8 ratio could be detected. The possible link between an altered immune state and post-vaccinal neuropathy is discussed.

CD4-CD8 Ratio↗

Adverse reactions to tick-borne encephalitis vaccine: FSME-Immun.

Vaccination against tick-borne encephalitis with FSME-Immun vaccine was started in the Department of Infectious Diseases, University Medical School of Białystok, Poland, in 1992. No serious adverse reactions after vaccine administration were observed. Post-vaccine side effects were reported in 242 (11.3%) persons after the first dose (n = 2,135) and only in 14 patients (1.2%) after the second one (n = 1,183). These effects were mild and transitory. No relationship was observed between the frequency of adverse reactions, general or local, and the initial anti-TBE virus antibody titres or the age of the immunized individuals. Post-vaccine side effects were reported significantly more frequently among people not bitten by ticks.

Adolescent↗

An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitis virus vaccine.

The live attenuated vaccine strain of Venezuelan equine encephalitis virus (VEEV), TC-83, protects mice against challenge (subcutaneous and aerosol) with virulent VEEV but is not suitable for widescale human use. Elucidation of the immune response profile of protected mice should assist in the development of an improved vaccine. We determined the optimum dose of TC-83 required to consistently protect Balb/c mice from airborne challenge with the virulent Trinidad Donkey strain of VEEV and studied the development of humoral and cellular immune responses in protected mice between 6 h and 21 days post-vaccination. The most dramatic immune responses occurred in draining lymph nodes 24 h following vaccination with increased levels of activated B cells and T cells of both CD4(+) and CD8(+) subtypes. Activated monocyte/macrophages and natural killer cells were also seen between 6 h and 7 days post-vaccination. Serum contained detectable VEEV-specific IgG on day 5 post-vaccination with titres continuing to rise on days 7, 14 and 21. Isotypes of IgG measured on days 7 and 21 were predominantly of the IgG2a subclass, indicating that the immune response was Th1-mediated. Cytokine mRNA was quantified by RT-PCR and revealed production of the Th1 cytokine IFN-gamma and the inflammatory cytokine TNF-alpha, whereas the Th2 cytokine IL4 was not detected above control levels at any of the time points studied. This data describes key cellular immune responses at early times post-vaccination and is consistent with previous data demonstrating protection against aerosol challenge with VEEV in the absence of detectable levels of specific IgG or IgA antibody.

Aerosols↗

Magnetic resonance imaging findings in acute cerebellitis.

Cerebellitis, also known as acute cerebellar ataxia, is an inflammatory syndrome of cerebellar dysfunction that may reflect an infectious, post-infectious, or post-vaccination disorder. We present serial magnetic resonance imaging (MRI) findings in a partially reversible, idiopathic cerebellitis. Bilateral cerebellar parenchymal abnormalities were noted, including hyperintensities on T2-weighted images and cerebellar swelling. After contrast administration, the cerebellum showed abnormal bilateral enhancement. The authors state this represents the first report of abnormal contrast enhancement in this condition. The MRI lesions most likely reflect the reversible, inflammatory nature of the syndrome.

Acute Disease↗

Immunological response in HIV-positive patients vaccinated against tick-borne encephalitis.

BACKGROUND: Vaccination against infectious diseases is a recommended preventive measure in patients with impaired immunity. The aim of the study was to estimate the immunogenicity of the vaccine against tick-borne encephalitis (TBE) in HIV-infected patients and to determine its safety for this group. PATIENTS AND METHODS: The TBE vaccine FSME-IMMUN-inject was tested on 29 HIV-positive patients and the response compared to that of 40 healthy controls. The vaccination protocol for the HIV-positive group was modified by the addition of a fourth dose according to a 0/1/2/9-month schedule. RESULTS: No serious adverse reactions were observed in patients with deficient immunity. A better response was obtained in HIV-infected patients with CD4 counts >or= 500/microl (55% of the patients had levels of IgG antibody > 126 VIEU/microl) than in those with CD4 counts of 200-499/microl (40%). However, the difference did not reach significance. 85% of healthy controls achieved protective antibody titers after a full course of vaccination. CONCLUSION: The correlation between post-vaccine seroconversion and CD4 lymphocyte count showed that the FSME-IMMUN-inject vaccine can be considered to be a CD4 cell-independent vaccine. The examinations carried out 1 year after the completed vaccination protocol showed maintenance of the anti-TBE response acquired after the third vaccination in healthy subjects and in HIV-infected patients.

Adult↗

Notes on the pathogenesis of subacute sclerosing panencephalitis.

In the original description by van Bogaert and De Busscher of subacute sclerosing leukoencephalitis (SSLE), great emphasis was placed upon the involvement of the white matter, a feature that, in addition to the absence of inclusion bodies, differentiated it from subacute inclusion body encephalitis (SIBE) of Dawson. Subsequently, the common features, primarily clinical, electroencephalographic and immunological led to the consolidation of both into the entity known as subacute sclerosing panencephalitis (SSPE). The white matter lesions of SSLE are identical to those that are seen in progressive rubella encephalitis, subacute AIDS encephalomyelitis, tropical spinal paraparesis due to HTLV-1, and visna of Icelandic sheep, but, more importantly, are characterized by the perivascular edema, inflammation and demyelination known in acute, immune-mediated post-infectious and post-vaccinal acute disseminated encephalomyelitis (ADEM). Furthermore, in SSLE and in the other conditions resulting from a persistent viral infection, deposits of immune complexes can be demonstrated in the walls of small cerebral blood vessels. There is therefore strong evidence to suggest that in SSLE as well as in the other persistent viral infections, in addition to the actual invasion by the virus, there is a contemporaneous immune-mediated response to this virus which is responsible for most, perhaps even all of the disseminated, extensive demyelination observed in these conditions. It is also suggested that SSLE and SIBE, sharing a common etiology, may represent two different phenotypic expressions of the same process.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Vaccination against tick-borne encephalitis under therapeutic immunosuppression. Reduced efficacy in heart transplant recipients.

Patients after organ transplantation are at an increased risk of microbial infections and might benefit from active vaccination. Due to therapeutic immunosuppression the efficacy of immunizations is, however, reduced and difficult to predict. Efficacy of vaccination against tick-borne encephalitis (TBE) using an abbreviated immunization schedule was compared in 31 heart transplant recipients (age: 54.5 +/- 11.5 years, mean time after transplantation: 53.5 +/- 23.7 months) under cyclosporine-based immunosuppression and 29 controls. TBE vaccination was well tolerated by the transplant recipients; spectrum and frequency of adverse events were similar to controls. In the transplant patients, seroconversion rate (35% versus 100%; p < 0.001) and the geometric mean of post-vaccinal antibody titres (0.98 (SF: 2.3) U/ml versus 5.46 (2.2) U/ml; p < 0.001) were markedly reduced in comparison to the control group. No clinical or demographic predictors of vaccination success could be established in the transplant patients. Due to the limited efficacy, TBE vaccination cannot be recommended as a routine procedure in heart transplant recipients at risk of TBE virus infection. TBE vaccination may be performed safely in selected cases, but repeated titre controls to confirm vaccination success would be required.

Adult↗

Development of a quantitative real-time RT-PCR assay with internal control for the laboratory detection of tick borne encephalitis virus (TBEV) RNA.

BACKGROUND: Tick borne encephalitis virus (TBEV), is a human flavivirus causing tick borne encephalitis (TBE), a viral infection of the central nervous system endemic in Europe and Asia. OBJECTIVES: To develop a reverse transcription polymerase chain reaction (RT-PCR) assay based on quantitative real-time RT-PCR technology (TaqMan) for detection and quantification of TBEV RNA. The test includes an internal control (IC) to avoid false negative results. STUDY DESIGN: The system was established and validated using wild-type (WT) non-infectious synthetic RNA representing a fragment of the 3' non-coding region of the TBEV genome. In addition, synthetic RNA differing from the WT synthetic RNA by a unique probe binding region was used as IC to monitor the overall efficiency of the RT-PCR. RESULTS: The analytical sensitivity of the assay was at least ten copies of the TBEV synthetic transcript in presence of 50 copies of the IC. Successful amplification was obtained for different strains within the TBEV complex (Hypr, Hochosterwitz, Laibach, Elsass=Alsace, ZZ9, Wladiwostok). Among 14 serum and 21 cerebrospinal fluid (CSF) samples obtained from 28 patients with clinical suspicion of TBEV 1 CSF sample tested positive for TBEV RNA. In addition, no TBEV RNA could be detected in blood samples obtained from three vaccinated people 1 and 3 days post-vaccination. Thus indicating that a positive result is unlikely to be caused by recent vaccination. CONCLUSIONS: A quantitative, highly sensitive and specific real-time RT-PCR assay has been developed for the detection of TBEV RNA. Inclusion of an IC is important to monitor the possible occurrence of false-negative results caused by the presence of inhibitory factors. This assay should be an important asset for the routine laboratory detection of TBEV RNA.

3' Untranslated Regions↗

Humoral response and protection from experimental challenge following vaccination of raccoon pups with a modified-live canine distemper virus vaccine.

Eight 8-wk-old raccoon pups (Procyon lotor) with maternal canine distemper virus (CDV) neutralizing antibodies (NAb) and 24 8-wk-old seronegative pups were administered a commercial modified-live CDV vaccine (Galaxy, D, Solvay Animal Health, Inc., Kitchener, Ontario, Canada). All 24 seronegative raccoons had detectable serum CDV NAb titers 14 days after the initial dose. Titers rose to maximum levels 4 wk post-vaccination. Mean titers for groups of vaccinated seronegative pups were maintained between 1:256 and 1:2,048 for the remainder of the 3 mo observation period. Geometric means of the serum CDV NAb titer of eight seronegative pups given a single vaccine dose at 8 wk of age did not differ significantly from those of eight pups that were given serial doses at 8, 12, and 16 wk of age, or from those of eight pups vaccinated once at 16 wk of age. Seven unvaccinated 8-wk-old raccoon pups used as controls remained seronegative throughout the trial. Seven out of eight 8-wk-old pups with maternal antibodies, vaccinated at 8, 12, and 16 wk of age, failed to develop a rise in their CDV NAb titers until at least 18 wk of age, 2 wk after the third vaccination. Titers in eight unvaccinated raccoons with maternal antibodies declined steadily to undetectable levels at 20 wk of age. A half-life of 10.55 days was calculated for maternally-derived CDV NAb in raccoon pups. Sixteen vaccinated raccoons were protected from clinical disease following experimental oronasal challenge with a virulent raccoon strain of CDV, 13 to 23 wk after vaccination. Serum CDV NAb titers at the time of challenge ranged from 1:12 to 1:384 and increased during the period of observation. Three of four unvaccinated seronegative raccoons used as controls failed to mount any detectable CDV NAb and were euthanatized after developing clinical signs of canine distemper 26, 29, and 30 days post-challenge (PC). Necropsies confirmed the diagnosis. The fourth control raccoon exhibited transient equivocal clinical signs, mounted a sluggish humoral response, but was clinically normal when euthanatized 42 days PC. In this raccoon, there was focal non-suppurative encephalitis with intranuclear inclusion bodies typical of CDV infection.

Animals↗

Neutralization antibody responses induced by Japanese encephalitis virus vaccine.

Single doses of Japanese encephalitis (JE) vaccine of the Nakayama strain were given to members of the staffs of a hospital and 99 paired-sera were obtained. Neutralization antibody titers of the sera were determined against the Nakayama strain and E-50 strain, isolated from wild Culex tritaeniorhynchus using clone C6/36 of Singh's Aedes albopictus mosquito cell culture. Post-vaccination sera showed a significant neutralizing antibody response against both the Nakayama and E-50 strain. The geometrical mean neutralization titers of post-vaccination sera against the Nakayama and E-50 strains were in the same order, although the geometrical mean neutralization titer against the Nakayama strain was the higher in pre-vaccination sera. The antibody responses against the Nakayama strain and E-50 strain were somewhat different in detail: 7 individuals with a pre-vaccination neutralization titers of less than 10 showed antibody responses to the Nakayama strain, whereas 3 individuals of the same group did not show any detectable response to the E-50 strain.

Antibody Formation↗