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At least 19 recordsLinked to original sources

Molecular typing of enteroviruses associated with viral meningitis in Cyprus, 2000-2002.

Human enteroviruses are responsible for a wide spectrum of clinical diseases affecting many different organ systems. Although infection is usually asymptomatic, infections of the central nervous system manifested as meningitis or encephalitis can pose a serious public health problem, especially during outbreaks. In this study, samples from 218 patients diagnosed with enteroviral meningitis between January 2000 and December 2002 were analysed in order to assess the epidemiology of human enteroviruses as a cause of viral meningitis in Cyprus. A new typing strategy, based on partial sequencing of the 5' non-coding region (5'NCR), prediction of type, and selection of type-specific primers for sensitive VP1 PCR amplification, was developed. As clustering in the 5'NCR was concordant with clustering in the VP1 region, quick and reliable typing by VP1 sequencing was achieved without virus isolation in cell culture. The most frequent enterovirus serotypes identified were Human echovirus 30 (55.5%), Human echovirus 13 (15.1%), Human echovirus 6 (13.8%) and Human echovirus 9 (8.3%). Human coxsackieviruses B2, B1 and B5, Human echovirus 4, Human enterovirus 71 and Human coxsackievirus A6 represented rather rare serotypes. This is the first molecular epidemiological study of enterovirus meningitis in Cyprus. Serotype distribution corresponded basically with observations in other European countries, suggesting the spread of enteroviruses by tourism.

5' Untranslated Regions↗

Persistence of echovirus 6 in cloned human cells.

Establishment of a persistent infection by echovirus 6 in cloned human WISH cells (PI) was demonstrated. The cloned human WISH cells were maintained for 3.0 years (over 125 passages) and released virus continuously without cellular destruction. Neither temperature-sensitive virus mutants nor interferon appears to play a role in either establishment or maintenance of viral persistence. The majority of the virus produced by cloned human WISH cells is defective (2 X 10(6) particles per PFU) and differs from standard virus in its polypeptide profile and its inability to attach to parental WISH cells.

Cells, Cultured↗

A mixed epidemic associated with echovirus types 6 and 11: virologic, clinical and epidemiologic studies.

During 1979, an outbreak of mixed enterovirus infections occurred in Kansas City and adjacent communities. Sixty-six enteroviruses and 7 adenoviruses were recovered from 73 persons in a survey hospital population. Twenty-eight persons yielded echovirus type 11, 22, echovirus type 6, and 16 either echovirus type 9 or Coxsackieviruses group B, types 2 and 3. This study describes some of the clinical, virologic and epidemiologic characteristics of the outbreak. A major finding relates to the recovery of enteroviruses from cerebrospinal fluids with essentially normal leukocyte counts.

Adenovirus Infections, Human↗

The histopathology of enterovirus infections of new-born mice.

For 32 years we have provided a routine histopathological service on animals for the Regional Virus Laboratory, Ruchill Hospital, Glasgow. This article concerns mainly experimental coxsackievirus A, coxsackievirus B and echovirus infections in new-born mice. In addition to previously reported findings, we have sometimes observed degenerative and inflammatory changes in neurons related to the Gasserian, posterior root or autonomic ganglia. Not all deposits of brown fat are simultaneously the seat of inflammatory changes; rarely, inflammation of brown fat spills over into the adjacent yellow adipose or connective tissues. Brown fat may occasionally show hyperplasia. Ballooning of the tips of small intestinal villi with interstitial oedema and/or necrosis of villous tips may indicate enanthemata associated with coxsackievirus A2,5,7,8,10,23 as well as with coxsackievirus B1 and B4 infections. Similar appearances were seldom seen with echovirus infections. Focal bone-marrow necrosis and necrosis of cartilage were associated with one coxsackievirus A10 infection, and osteitis with one coxsackievirus B3 infection. The implications of these uncommon observations for human pathology remain to be determined.

Adipose Tissue, Brown↗

Zoster-like eruption due to echovirus 6.

A unilateral vesiculobullous eruption associated with fever was seen on the neck, shoulder, and upper part of the chest of a 7-year-old boy. Although three dermatomes in all were involved, the lesions resembled herpes zoster. The patient had had varicella in infancy. Culture of fluid from several bullae yielded echovirus 6; however, and serum neutralizing antibody to this virus rose in titer from 1:32 to 1:640. It is suggested that echovirus 6 and other enteroviruses may cause a number of vesicular eruptions that resemble herpes zoster and similar infections. Viral culture, while often difficult to obtain, is the only way to identify the cause of eruptions like this one.

Child↗

Simultaneous onset of type 1 diabetes mellitus in identical infant twins with enterovirus infection.

This report describes classical Type 1 insulin deficient diabetes mellitus (DM) arising in twins aged 14 months, both of whom had evidence of enterovirus infection. The diagnosis of Type 1 DM was made in the second twin within 12 days of the first. Enterovirus infection was detected in each twin at diagnosis by polymerase chain reaction (PCR). Both twins were negative for enterovirus by PCR 5 months following diagnosis, although both were then positive for islet cell antibodies. Sequencing of the amplicons produced by PCR suggested that the viruses from each twin were not the same but that they were both variants related to echovirus 6.

Age of Onset↗

Intrathecal synthesis of immunoglobulins in Neisseria meningitidis and echovirus 6 meningoencephalitis.

Infectious diseases of the central nervous system (CNS) constitute the main cause of death amidst the neurological diseases in pediatric patients in Cuba. This factor, among others, made us study the immune response in children with such disorders. Cerebrospinal fluid (CSF) and serum samples were collected from 69 patients: 26 with Neisseria meningitidis meningoencephalitis, and 43 with echovirus 6. IgA, IgM, IgG, and albumin were measured by immunodiffusion in serum and CSF. Local synthesis of immunoglobulins was calculated using Reiber's formula. The detection of intrathecal synthesis of IgG represents an important event in the majority of cases. Detection depends on the acuity of the process, the nature of the biologic agent and its virulence, and the immunological status of the patient. Local IgG synthesis is a very frequent finding in Neisseria meningoencephalitis and echovirus 6 meningoencephalitis. Intrathecally synthesized IgA in patients suffering from N. meningitidis meningoencephalitis is an important indication.

Adolescent↗

Neonatal Type I diabetes associated with maternal echovirus 6 infection: a case report.

AIMS/HYPOTHESIS: Neonatal diabetes mellitus is rare, and it has not been associated with beta-cell autoimmunity. Enteroviral infections during pregnancy have been implicated as a risk factor for the later development of Type I (insulin-dependent) diabetes mellitus. We now report of a baby girl who was born severely growth-retarded with neonatal insulin-deficient diabetes, and look for evidence of intrauterine enteroviral infections and beta-cell targeted autoimmunity. METHODS: Diabetes-associated autoimmunity was studied by measurement of several types of islet cell reactive autoantibodies. The infant's T-cell responses to insulin and enterovirus antigens were recorded and enterovirus antibodies were measured both from the mother and the child. RESULTS: Several types of diabetes-associated autoantibodies were detected postnatally, including insulin autoantibodies, conventional islet cell autoantibodies and glutamic acid decarboxylase antibodies, whereas no autoantibodies were observed in the mother. The infant's T-cells showed reactivity to insulin and purified enterovirus particles. Based on serological studies, the pathogenetic process could have been triggered by an echovirus 6 infection during pregnancy. The patient's diabetes has been permanent, although there were signs of endogenous insulin production for several months. Exocrine pancreatic insufficiency was diagnosed at the age of 1 year. CONCLUSION/INTERPRETATION: These observations suggests that enteroviral infections may induce beta-cell autoimmunity even in utero.

Autoimmunity↗

Molecular phylogeny of VP1, 2A, and 2B genes of echovirus isolates: epidemiological linkage and observations on genetic variation.

Phylogenetic relationships between 37 echovirus clinical isolates, most of them originating from an aseptic meningitis outbreak during 2001 in Greece, were investigated by RT-PCR and sequencing. The generic primers 292 and 222 were used to amplify about 300 bp of the 5' end of VP1 while primers EUG3a, 3b, 3c, and EUC2 amplified the entire coding sequence of the 2A and 2B genes. Phylogenetic trees were constructed for each genomic region using the clinical isolates' sequences and those of the prototype echoviruses in order to investigate the correlation of part of VP1 with the serotype as well as the genetic variation of the echovirus genome in 2A and 2B. The phylogenetic grouping pattern of the clinical isolates revealed that there is a correlation of serotype and genotype in the part of VP1 that was investigated, while this pattern is disrupted in the adjacent genomic regions that were sequenced. Sequence analysis of the adjacent 2A and 2B genes provided a different pattern of phylogenetic relationships and strong evidence of epidemiological linkage of most of the clinical isolates.

Amino Acid Sequence↗

Cumulative mutations in the genome of Echovirus 6 during establishment of a chronic infection in precursors of glial cells.

Although Enteroviruses are mainly described as responsible for acute diseases, their role in severe chronic pathology has been also established. Echovirus 6-like sequences have been detected by PCR analysis in central nervous system specimens from patients presenting with Amyotrophic Lateral Sclerosis. These findings suggested a persistent infection with viruses that underwent, genetic changes precluding viral particle release. To support this hypothesis, we developed a model system of Echovirus 6 chronic infection in precursors of glial cells. The nucleotide sequences of the 5'non-translated region (5'NTR), 2A and 3C regions of the virus developing persistent genome were analysed during establishment of the chronic phenotype. This study revealed that at day 160 of chronic infection, several mutations were observed: one mutation at nucleotide 108 upstream the domain II of the internal ribosome entry site (IRES) structure, one mutation at nucleotide 30 in the cloverleaf, and two mutations in the 2A region (translated in His48 to Tyr, and Ile 123 to Met). No mutations were detected in the 3C region. The impact of these mutations on viral replication have been analysed in a rabbit reticulocyte lysate (RRL) translation assay supplemented with HeLa cell lysate, and by plaque assay. Viruses with these mutations displayed a phenotype with a significant reduction of replication, while in vitro translation was not affected by the nucleotide 108 mutation. This model allowed the description of molecular changes observed in the genome of Echovirus 6 during the establishment of a chronic infection phenotype, and may be helpful for the understanding of the mechanisms leading Enteroviruses to develop chronic infections in man.

5' Untranslated Regions↗

[Lymphocytic meningitis in Spain: a possible epidemic situation in 2000].

UNLABELLED: In order to clarify the unexpected increase in 2000 of lymphocyticmeningitis analyzed in the Centro Nacional de Microbiología,Instituto de Salud Carlos III, Madrid, here we present their microbiological features. PATIENTS AND METHOD: Samples of 732 patients were tested by virological and serological methods to detect infections by neurotrophic agents. RESULTS: Infections were identified in 375 (51%) cases. Nopolio enteroviruses were identified in 90% cases. Echovirus 30 and 13 were mainly characterized, the latter for the first time in Spain. CONCLUSIONS: The emergence of Echovirus 13 may explain the past epidemic situation.

Adolescent↗

Viral meningitis due to echovirus types 6 and 9: epidemiological data from Western Australia.

During the autumn of 1992, Western Australia experienced a large viral meningitis outbreak of dual aetiology. Of the 161 cases, 64% were children under 15 years of age, with the highest notification rate being in children less than 5 years of age. Echovirus 9 caused 41% of cases and occurred mainly in the metropolitan areas of Western Australia whereas echovirus 6, which caused 37% of cases, was more widespread. An enterovirus was cultured from 70% of CSF specimens, 88% of faecal specimens and 68% of upper respiratory tract specimens. High CSF white cell counts and neutrophil predominance were common. Seven cases had normal CSF white cell counts even though an enterovirus was isolated from the CSF. Therefore, the CSF findings were of restricted value in excluding viral meningitis, and did not reliably distinguish between bacterial and viral meningitis.

Adolescent↗

Fatal neonatal echovirus 6 infection: autopsy case report and review of the literature.

A full-term, healthy male neonate was delivered by caesarian section to a 26-year-old primigravida woman who had a history of fever and upper respiratory tract infection. On the fourth day of life, the neonate developed a sepsis-like syndrome, acute respiratory and renal failure, and disseminated intravascular coagulopathy. He died 13 days after birth. Postmortem examination revealed jaundice, anasarca, massive hepatic necrosis, adrenal hemorrhagic necrosis, renal medullary hemorrhage, hemorrhagic noninflammatory pneumonia, and severe encephalomalacia. Echovirus type 6 was isolated from blood, liver, and lungs. Although uncommon, echovirus type 6 infection may produce a spectrum of pathologic findings similar to those seen with the more commonly virulent echovirus type 11.

Adrenal Glands↗

[Intrathecal interferon therapy in chronic echovirus meningoencephalitis in Bruton type agammaglobulinemia].

A 9-year-old body with X-linked agammaglobulinemia developed chronic enteroviral meningoencephalitis (CEMA) caused by echovirus type 6. Intravenous treatment with selected immunoglobulin charges containing high titers against echovirus type 6 or combination with beta-interferon did not result in improvement. After implantation of a Rickham reservoir and periodical administration of intraventricular and intravenous immunoglobulin the virus recurred rapidly each time treatment was stopped. After 20 months of treatment the patient received a combined therapy with beta-interferon and selected immunoglobulin. Both drugs were given by lumbar puncture, intravenously and via Rickham reservoir. Subsequently echovirus type 6 could not be isolated in culture or PCR. Cerebrospinal fluid pleocytosis disappeared. The remission is lasting for more than three years. Intrathecal and intraventricular beta-interferon therapy for CEMA is being reported for the first time. Facing the unfavourable prognosis of the disease this mode of treatment is a new therapeutic approach following failure of other therapies.

Agammaglobulinemia↗