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PubMed1995

Neonatal enterovirus infection.

A neonate who had a nonfatal echovirus 11 infection with severe hepatitis, hepatic necrosis, disseminated intravascular coagulation, and thrombocytopenia was seen at the University of Tennessee Medical Center (UTMC) in Knoxville. Clinical data from this neonate were examined and compared with clinical data from histories of 8 other cases of neonatal enteroviral infections seen at UTMC, Knoxville, during a 3-year period. The purpose of our study was to increase awareness of the clinical presentations of neonatal enteroviral infections, especially in summer months. The patients in our study presented with various clinical manifestations of disease, including overwhelming systemic infection characterized by severe hepatic dysfunction and coagulopathy with possible disseminated intravascular coagulation and central nervous system infection. Myocarditis was sometimes manifested as well. In agreement with findings from other studies, our study concluded that most enteroviral infections in neonates resulted from perinatal transmission during delivery where the mothers had experienced recent, febrile, viral-like illness prior to or during delivery. One uncommon finding in our study was that the cases were strikingly seasonal, with 8 of the 9 infants hospitalized during late summer or early fall (July through September).

Age of Onset↗

PubMed2000

Cardiac manifestations of fatal enterovirus infection during the 1998 outbreak in Taiwan.

BACKGROUND: An outbreak of hand-foot-and-mouth disease caused by enterovirus infection occurred in Taiwan in 1998 and more than 70 infants and children with fulminant courses died. We compared the cardiac manifestations of fatal cases with patients who survived the enterovirus infection. METHODS: A total 187 patients with enterovirus infection were treated at Taichung Veterans General Hospital between April and June 1998. Enterovirus infection was diagnosed by history, clinical features, polymerase chain reaction study and/or viral culture. Cardiac examinations including complete physical examinations, electrocardiography and echocardiography were performed on seven cases (group I) with or without central nervous system (CNS) involvement, 30 patients with CNS involvement (group II), and 150 patients without CNS involvement (group III). RESULTS: There were no significant differences in sex distribution, days of fever, heart rate, systemic blood pressure or time from the onset of symptoms to hospital admission among the three groups. All group I patients had features of acute congestive heart failure, pulmonary edema and neurologic signs except one who presented with right-sided heart failure and neurologic signs. The echocardiographic findings of group I were a lower fractional shortening, lower ejection fraction, and more severe and higher incidence of mitral regurgitation (p < 0.01) than in groups II and III, but there were no significant differences in end-systolic wall stress, left ventricular end-diastolic internal dimension and incidence of pericardial effusion among the three groups. CONCLUSIONS: We conclude that seven infants and children (group I) died due to either severe cardiomyopathy or encephalopathy. The possible pathogenesis of enterovirus infection leading to death is reviewed and analyzed.

Brain Diseases↗

PubMed2004

Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project.

The incidence of type 1 diabetes varies markedly between countries. As enterovirus infections have been linked to type 1 diabetes, we determined whether this variation correlates with the frequency of enterovirus infections in different Caucasian populations in Europe. Enterovirus antibodies were examined in the background population (1-year-old and 10-14-year-old children) in seven countries with either exceptionally high (Finland and Sweden) or low/intermediate incidence of diabetes (Estonia, Germany, Hungary, Lithuania, Russia) using EIA and neutralisation assays. Enterovirus antibodies were less frequent in countries with high diabetes incidence compared to countries with low diabetes incidence (P<0.001). This suggests that enterovirus infections are not particularly common in countries with high diabetes incidence. In contrast, there seems to be an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population, which is in line with the previously proposed polio hypothesis according to which the complications of enterovirus infections become more common in an environment with a decreased rate of infections.

Adolescent↗

PubMed1998

Usefulness of nested PCR and sequence analysis in a nosocomial outbreak of neonatal enterovirus infection.

BACKGROUND: Non-polio enterovirus infections are recognized in children during summer-fall seasons and they sometimes cause large outbreaks. We experienced a nosocomial infection in the neonatal nursery and echovirus type 7 was isolated from samples of four patients. OBJECTIVES: We diagnosed the horizontal infection of four neonates by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and the nucleotide sequence. STUDY DESIGN: Total RNA was extracted from clinical isolates, serum samples and cerebrospinal fluid (CSF). We amplified enterovirus genome in the 5'-noncoding region by nested PCR and determined the nucleotide sequences. RESULTS: Enterovirus genome was detected in all isolates, in the acute-phase sera in all four patients and in the CSF in one patient by the first PCR. By using nested PCR, the genome was detected from convalescent-phase sera in two patients. All enterovirus genome obtained from the nursery outbreak showed the same sequences with 100% homology. CONCLUSION: We demonstrated the clinical advantages of RT-nested PCR from serum samples and the analysis of nucleotide sequencing gave the supportive evidence of identification of transmission pathway.

5' Untranslated Regions↗

PubMed2003

Diagnosis of enterovirus infection in the first 2 months of life by real-time polymerase chain reaction.

During summer and fall, enterovirus infections are responsible for a considerable proportion of hospitalizations of young infants. We prospectively studied the incidence of enterovirus infections via real-time polymerase chain reaction (PCR) in blood, feces, and cerebrospinal fluid samples from infants <or=60 days old who had received a clinical diagnosis of sepsis. Forty-five patients were included: 19 were admitted to the pediatric wards of 2 general hospitals, and 26 had been hospitalized since birth in the neonatal intensive care unit (NICU) of a tertiary care hospital. None of the NICU patients developed enteroviral disease. In contrast, an enterovirus was detected in 11 (58%) of the patients admitted to the 2 general hospitals, 10 of whom (53%) showed evidence of systemic infection. Enterovirus infections are an important cause of sepsis in infants admitted to the hospital. Real-time PCR in serum was a rapid and sensitive method for diagnosis of enterovirus infection.

Enterovirus↗

PubMed2004

Enterovirus infections following T-cell depleted allogeneic transplants in adults.

Anecdotally, enteroviruses have been reported to cause serious complications post BMT, but the exact impact of these viruses in the post transplant period has not been reported. We prospectively evaluated stool, urine and throat samples for enteroviruses by viral culture together with relevant body fluids by RT-PCR in 64 allograft recipients receiving grafts T-cell depleted by Campath-1H, following both conventional and reduced-intensity conditioning. Seven patients (10.4%) developed nine episodes of enterovirus infections at a median of 146 days post transplant. Four episodes were associated with symptomatic illnesses, which could be attributable to enteroviruses. There was no mortality directly related to enteroviruses. There was no correlation between dose and mode of Campath-1H use, lymphocyte recovery, IgG and IgA levels and enterovirus isolation. Although enteroviruses tended to be more frequent in TBI-based conventional conditioning recipients, the only significant risk factor for enterovirus infection was unrelated donor graft. The low incidence of the severe enterovirus infections could have been related to a low lymphocyte count in this cohort in the absence of GVHD, particularly CD4+ count, which has been implicated in tissue damage in experimental animals. Further studies are needed to define its impact in different allograft settings.

Adolescent↗

PubMed2000

Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study.

Previous studies suggest that enterovirus infections may initiate and accelerate beta-cell damage years before the clinical manifestation of type 1 diabetes. We have now analyzed the role of enterovirus infections in the initiation of autoimmunity in children who have tested positive for diabetes-associated autoantibodies in a prospective study starting at birth (the Finnish Diabetes Prediction and Prevention Study). The frequency of enterovirus infections was studied using both serology and testing for the presence of enterovirus RNA in the sera of 21 children who developed and retained autoantibodies and in 104 control subjects chosen from the same study cohort and matched for the time of birth, sex, and HLA alleles determining genetic diabetes susceptibility. Sample intervals were taken as basic units of follow-up, to which the observed number of infections was adjusted. Enterovirus infections were detected in 26% of sample intervals in the case subjects and in 18% of the sample intervals in the control children (P = 0.03). A temporal relationship between enterovirus infections and the induction of autoimmunity was found; enterovirus infections were detected in 57% of the case subjects during a 6-month follow-up period preceding the first appearance of autoantibodies compared with 31% of the matched control children in the same age-group (odds ratio 3.7, 95% CI 1.2-11.4). The frequency of adenovirus infections did not differ between the patient and control groups. Our data imply that enterovirus infections are associated with the development of beta-cell autoimmunity and provide evidence for the role of enteroviruses in the initiation of beta-cell destruction.

Alleles↗

PubMed1998

Enterovirus infections and insulin dependent diabetes mellitus--evidence for causality.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) has a long subclinical period characterised by gradually progressing autoimmune damage of insulin producing beta-cells. Clinical IDDM is manifested when 90% of beta-cells have been destroyed. Several studies have indicated that enterovirus infections, coxsackievirus B (CVB) infections especially, are frequent at the manifestation of clinical IDDM suggesting that they can precipitate the symptoms of IDDM in individuals who already have an advanced beta-cell damage. Recently, the first prospective studies have been published suggesting that enterovirus infections can also initiate the process several years before clinical IDDM. This implies that enterovirus infections may have a crucial role in the pathogenesis of human IDDM. OBJECTIVE: The recent findings have brought up the question whether the time has come when a causal association between enterovirus infections and IDDM could finally be confirmed. This review focuses on this question summarising the current knowledge and the prospects of future research. STUDY DESIGN: Review of the recent progress in studies evaluating the role of enterovirus infections in human IDDM. CONCLUSIONS: The currently available information supports the assumption that the role of enterovirus infections may be more important than previously estimated. Enterovirus infections are obviously associated with increased risk of IDDM, but whether this association reflects causal relationship remains to be confirmed in future studies. Prospective birth-cohort studies will be among the most important ones giving important data on the etiologic fraction of enterovirus infections, the properties of diabetogenic virus variants and the mechanisms of beta-cell damage.

Diabetes Mellitus, Type 1↗

PubMed1997

[Western blotting in the serologic diagnosis of enterovirus infections. I. Detection of coxsackie virus antibodies in reference sera and sera of experimentally infected mice].

The introduction of rapid serological diagnosis of enterovirus infections is faced with the problem of inter-type cross-reactions. Therefore the method of choice is still the virus-neutralization test on cell cultures and on suckling mice resp., i.e. methods which are expensive and time consuming and demanding on laboratory equipment. The detection of antibodies against the Coxsackie virus by means of Western blotting revealed a specific reaction of commercial hyperimmune diagnostic rabbit as well as of sera obtained after oral infection of mice. The application of the method in the diagnosis of human enterovirus infections will be the subject of the subsequent part of this study.

Animals↗

PubMed1975

Sequelae of central-nervous-system enterovirus infections.

The long-term effects of central-nervous-system enterovirus infections were examined in a controlled follow-up study of 19 children 2 1/2 to eight years of age who had been hospitalized with documented enterovirus infection 17 to 67 months before evaluation. Assessment included medical history, physical and neurologic examination, psychologic testing, and speech and hearing evaluation. Three children (16 per cent) had definite neurologic impairment, five (26 per cent) had possible impairment, and 11 (58 per cent) were free of detectable abnormalities. Children whose illness occurred during the first year of life, when compared to controls, were found to have significantly smaller mean head circumference (50.6 vs. 51.6 cm, P less than 0.033), significantly lower mean I.Q. (97 vs 115, P less than 0.007), and depressed languange and speech skills. Children whose illness occurred after the first year of life were not different from their controls. Children whith central-nervous-system enterovirus infection may have neurologic impairment when infection occurs in the first year of life.

Age Factors↗

PubMedDate not supplied

Identification of trophoblastic giant cells as the initial principal target of early gestational murine enterovirus infection.

Theiler's murine encephalomyelitis virus (TMEV), a murine enterovirus, infects the majority of murine placentae and fetuses following inoculation in early gestation and infects most placentae but almost no fetuses in late gestation. The sequence of infection of TMEV following early gestation inoculation was studied. Mice were inoculated with TMEV on day 6 or 7 of pregnancy and sacrificed at intervals between 1 h and 4 days later. Culture of placenta-embryo units identified infection at 2, 3, and 4 days post-inoculation. In situ hybridization revealed TMEV RNA primarily in giant cells around the yolk cavity and in giant cells situated between the decidua and spongiotrophoblast layers of the placenta. Occasional decidual cells located near giant cells were also hybridization-positive. The giant cells were immunohistochemically identified as fetally derived trophoblast cells. Giant cells are the earliest predominant target of TMEV infection following early gestation inoculation and appear to be an integral part of the pathogenesis of gestational murine enterovirus infection.

Animals↗

PubMedDate not supplied

Enterovirus infections in Germany: comparative evaluation of different laboratory diagnostic methods.

BACKGROUND: The diagnosis of an enterovirus infection may be achieved through direct virus detection from fecal or cerebrospinal fluid (CSF) samples by virus isolation or PCR. Serologically, a significant rise in antibody titer may be detected and different enteroviral types can be differentiated using the neutralization assay. PATIENTS AND METHODS: We investigated the contribution of these different laboratory parameters to the diagnosis of enterovirus infections occurring in the Frankfurt am Main area during the years 1997 to 1999, including an echovirus 30 outbreak in a group of children with aseptic meningitis in 1997. Samples were referred from 1,013 patients; virus isolation was attempted from 579 CSF specimens and from 400 stool samples. 208 CSF samples were tested by PCR. RESULTS: During the echovirus 30 outbreak we identified 22.3% of samples as positive, almost exclusively echovirus 30. In 1998 only 7.1% of samples were positive and a rather broad range of agents was isolated. In 1999 10.4% were positive, predominantly coxsackie B5 and echovirus 11. We could show that in acute enterovirus infections, virus detection by cell cuLture and PCR is superior to serological methods (neutralization assay and IgM assay). For virus isolation, there was a higher rate of positives from stool compared to CSF (1997: 27.8% versus 25%; 1998: 14.4% versus 3%; 1999: 17.9% versus 8.5%). When comparing PCR and virus isolation from the CSF, the former yielded a higher rate of positive results but was not clearly superior to virus isolation from CSF. CONCLUSION: The recommended method for the diagnosis of acute enterovirus infections is virus isolation from feces. In cases of suspected aseptic meningitis virus isolation and PCR are valuable for the direct detection of virus in CSF.

Acute Disease↗

PubMed2002

Maternal first-trimester enterovirus infection and future risk of type 1 diabetes in the exposed fetus.

Previous studies have suggested that enterovirus infections during pregnancy may increase the risk of type 1 diabetes in the offspring. Our aim was to evaluate the role of first trimester enterovirus infections in a larger cohort of pregnant women. Two series of pregnant women were analyzed as follows: 948 women (series 1) and 680 women (series 2) whose child developed clinical diabetes before the ages of 15 or 7 years, respectively. An equal number of control women with a nondiabetic child was selected. Acute enterovirus infections were diagnosed by measuring IgM class antibodies against coxsackievirus B5 (series 1) and a mixture of coxsackievirus B3, coxsackievirus A16, and echovirus 11 antigens (series 2). In series 2, all sera were also analyzed for IgG class antibodies against an enterovirus peptide antigen. In addition, 152 randomly selected case-control pairs and all IgM-positive mothers' sera were tested for enterovirus RNA (series 2). In series 1, 3.1% of case women had IgM antibodies against coxsackievirus B5 antigen compared with 4.1% of control women (NS). In series 2, 7.1% of case and 5.3% of control women had IgM against the mixture of enterovirus antigens (NS). IgG class enterovirus antibodies did not differ between the groups. Enterovirus RNA was found only in one case woman (0.3%) of the subgroup of samples and in 5.7% of 70 IgM-positive women. The results suggest that enterovirus infection during the first trimester of pregnancy is not associated with increased risk for type 1 diabetes in the child.

Antibodies, Viral↗

PubMed2003

Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial.

This study evaluated the possible role of enterovirus infections in the pathogenesis of type I (insulin-dependent) diabetes in a prospective dietary intervention trial. Children participated in the second pilot of the Trial to Reduce IDDM in Genetically at Risk (TRIGR) project. They were randomized into two groups receiving either a casein hydrolysed formula (Nutramigen) or a regular formula, whenever breast milk was not available over the first 6-8 months of life. Altogether 19 children who turned positive for autoantibodies associated with type I diabetes by 2 years of age and 84 matched control children were analysed for enterovirus antibodies and enterovirus RNA in serum. Enterovirus infections were common during the first 2 years of life and more frequent among boys than girls (P = 0.02). Autoantibody-positive children had more enterovirus infections than autoantibody-negative children before the appearance of autoantibodies (0.83 versus 0.29 infection per child, P = 0.01). The average levels of IgG antibodies to echovirus antigen were also higher in autoantibody-positive than in autoantibody-negative children (P = 0.0009). No difference was found in the frequency of enterovirus infections between children receiving the casein hydrolysed formula or regular formula. These results suggest that enterovirus infections are associated with the induction of beta-cell autoimmunity in young children with increased genetic susceptibility to type I diabetes.

Antibodies, Viral↗

PubMed1989

Intrathecal synthesis of virus-specific oligoclonal antibodies in patients with enterovirus infection of the central nervous system.

Cerebrospinal fluid (CSF) and serum samples from six patients with enterovirus infections were investigated by isoelectric focusing (IEF) and affinity-mediated immunoblot AMI) for the clonal distribution of entervirus-specific antibodies. In two patients with either acute meningitis or encephalitis and in one patient with a relapse of multiple sclerosis, oligoclonal IgG bands specific for enteroviruses were found predominantly in the CSF, revealing intrathecal synthesis of these antibodies. In three other patients with neurological symptoms probably unrelated to a current enterovirus infection, IEF and AMI disclosed nearly identical patterns of coxsackievirus-B-specific oligoclonal bands in the CSF and serum, indicating diffusion of these antibodies from the serum into the CSF. Although the number of patients in this study is small, the results suggest that intrathecally synthesized enterovirus-specific antibodies may be used as a means of identifying an enterovirus infection of the CNS.

Adult↗

PubMed1979

Enterovirus infection in a semi-closed community.

Infection with enteroviruses was studied over a 61-week period (during 1960-61) in a semi-closed child community in the Detention Home of the Allegheny County Juvenile Court in Pittsburgh, Pennsylvania. While most of the viruses isolated were known adeno- and enterovirus types, three apparently represent new enterovirus types or 'prime strains'. Viruses were isolated in all but 6 weeks of the 61-week study period from the gastro-intestinal tracts of 110 children out of a total population of 514 (21%); of these 110, 24 children (22%) excreted virus at the time of admission. The population averaged 37 children (more than half of whom were under 5 years of age), with a turnover of about nine per week. Spread of infection in this community on introduction of a new virus was demonstrated, with virus shedding of variable duration after infection. Thirteen of the 110 positive children (12%) showed mixed virus infections. During the entire study period, no clinical diarrheal illness was found associated with the viral infections detected.

Adenoviruses, Human↗

PubMed1987

Enterovirus and enterovirus infections.

An account of the nature of enterovirus and enterovirus infections with special reference to experiences encountered in Singapore is presented. The most common of enterovirus epidemic diseases since 1970 is Acute Haemorrhagic Conjunctivitis caused by Coxsackievirus A24 variant and Enterovirus type 70. Enterovirus of various serotypes were isolated from a wide range of illnesses varying in severity throughout the year.

Conjunctivitis, Viral↗

PubMed1999

[Enterovirus infections in children under three months of age].

Enterovirus infections in childhood (echoviruses, coxsackie viruses A and B, unclassified enteroviruses) are varied, nonspecific and benign (except for poliovirus infections). However, in infants, they may lead to severe neurological or cardiac lesions. In neonates, enterovirus infections are difficult to distinguish from late-onset bacterial infection. Maternal-fetal or postnatal transmission can induce early spontaneous abortions or severe neonatal infections. Diagnosis is usually based on viral cultures and, in recent years, on PCR techniques. At the present time, no potential effective drug is available: intravenous immunoglobulins, immunization or anti-proteases may be of interest.

Diagnosis, Differential↗