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PubMed2002

Development and evaluation of nucleic acid sequence based amplification (NASBA) for diagnosis of enterovirus infections using the NucliSens Basic Kit.

BACKGROUND: Molecular methods based on RNA amplification are needed for sensitive detection of enteroviruses in clinical samples. Many 'in house' methods based on reverse-transcribed PCR (RT-PCR) could be difficult to use in the routine diagnostic laboratory since they tend to be time-consuming, use reagents from many different suppliers and include non-routine procedures. OBJECTIVES: The aim of this study was to develop and evaluate methods based on nucleic acid sequence based amplification (NASBA) for detection of enterovirus sequences. STUDY DESIGN: 'In house' prepared and commercially available reagents were utilised to develop enterovirus-specific NASBA assays. Optimised methods were evaluated using clinical samples (cerebrospinal fluid, respiratory and stool samples), titred virus controls and in vitro produced synthetic RNA. Results for NASBA were compared with RT-PCR and virus culture. RESULTS: Kit-based reagents gave an equivalent sensitivity to the more laborious 'in house' molecular assays (NASBA and RT-PCR) on clinical material and controls. All molecular methods picked up enterovirus positive clinical samples that were not identified by culture. End point detection sensitivity for the NASBA assay based on the NucliSens Basic Kit was <or=1 tissue culture infective dose 50% of a range of enteroviruses or <100 copies RNA input. The assay was specific for enteroviruses and did not pick up high titre rhinovirus preparations. Enterovirus Basic Kit NASBA results for clinical samples were easily obtained within a single working day. CONCLUSIONS: NASBA is a suitable alternative to RT-PCR for sensitive amplification and detection of enterovirus sequences in a range of clinical specimens. The use of kit-based reagents will enable a wide range of laboratories to undertake molecular-based diagnostic procedures for RNA viruses and provide results within a time frame relevant to patient management.

Enterovirus↗
PubMed1997

Detection and rapid differentiation of human enteroviruses following genomic amplification.

By employing a nested PCR (n-PCR) with specific primers derived from the 5' nontranslated and consensus region of the human enterovirus genome, we detected enterovirus RNA from 32 different serotypes of prototypic strains. A specific 297-bp fragment was amplified by this method from all of these strains. Not only was the method highly sensitive, detecting enterovirus RNA extracted from 0.01 50% tissue culture infective dose/50 microl (which is more sensitive than our current routine method of enterovirus diagnosis, based on the virus isolation and serotypic neutralization), but it was also relatively rapid. By using this technology, we also detected enterovirus RNA in uncultured specimens (including throat swabs and stools) from patients with respiratory illness and acute flaccid paralysis syndrome. This method enabled us to rapidly and directly distinguish enterovirus-infected specimens from nonenterovirus specimens in laboratory diagnosis. Furthermore, restriction fragment length polymorphism was assessed as an alternative means of differentiating various serotypes of prototypical enteroviruses. Fourteen of 16 human enterovirus-infected specimens exhibited restriction patterns identical to those of the corresponding prototypes.

Enterovirus↗
PubMed2005

High frequency of human enterovirus species C circulation in Madagascar.

Four poliomyelitis outbreaks caused by vaccine-derived polioviruses have been reported recently, including one in Madagascar in 2002. In all cases, the viral strains involved were recombinant between poliovirus vaccine strains and nonpoliovirus strains, probably enterovirus species C. Nevertheless, little is known about the circulation and epidemiology of enteroviruses in the regions where these outbreaks occurred. To assess the circulation of enteroviruses (particularly enterovirus species C) in Madagascar, we genetically characterized 55 enterovirus strains isolated between 1994 and 2002. The strains were identified and compared by partially sequencing the region encoding the VP1 capsid protein. Phylogenetic analysis and pairwise comparison with prototype enterovirus strains distinguished two different species: 25 isolates belonged to human enterovirus B species, and 30 isolates were identified as coxsackievirus A13, A15, A17, A18, A20, A21, and A24, belonging to the human enterovirus species C. The relatively high frequency and the wide distribution of species C coxsackie A viruses in different regions of Madagascar suggest that they had been silently and widely circulating in the country during the whole study period. The circulation of coxsackie A viruses, combined with the low routine oral polio vaccine coverage, may have played a role in the emergence of the recent outbreak in Madagascar.

Amino Acid Sequence↗
PubMed2003

Enterovirus related metabolic myopathy: a postviral fatigue syndrome.

OBJECTIVE: To detect and characterise enterovirus RNA in skeletal muscle from patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle energy metabolism in enterovirus positive and negative CFS patients. METHODS: Quadriceps muscle biopsy samples from 48 patients with CFS were processed to detect enterovirus RNA by two stage, reverse transcription, nested polymerase chain reaction (RT-NPCR), using enterovirus group specific primer sets. Direct nucleotide sequencing of PCR products was used to characterise the enterovirus. Controls were 29 subjects with normal muscles. On the day of biopsy, each CFS patient undertook a subanaerobic threshold exercise test (SATET). Venous plasma lactate was measured immediately before and after exercise, and 30 minutes after testing. An abnormal lactate response to exercise (SATET+) was defined as an exercise test in which plasma lactate exceeded the upper 99% confidence limits for normal sedentary controls at two or more time points. RESULTS: Muscle biopsy samples from 20.8% of the CFS patients were positive for enterovirus sequences by RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS patients had a SATET+ response. Nine of the 10 enterovirus positive cases were among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET- patients. PCR products were most closely related to coxsackie B virus. CONCLUSIONS: There is an association between abnormal lactate response to exercise, reflecting impaired muscle energy metabolism, and the presence of enterovirus sequences in muscle in a proportion of CFS patients.

Adult↗
PubMed2003

[Detection of nonpoliomyelitic enteroviruses in central nervous system infections in Poland in 1995-2000; viral isolation data].

The aim of this study was evaluation of enterovirus diagnosis based on isolation of the virus in cell culture from subjects with aseptic neuroinfection conducted in six Provincial Sanitary-Epidemiological Stations in 1995-2000 years. Available data from six Sanitary-Epidemiological Stations indicated that 1429 isolation of enteroviruses from fecal samples of those patients were performed. The most frequently isolated enterovirus serotype was echovirus type 30: 138/203 isolated enteroviruses, but also others enterovirus serotypes were isolated in a study period. In the years 1995 and 1996 the percentage of positive results of isolation was highest with the numbers of 31% and 28.27% respectively. The decrease in positive isolation results has been observed from 1997 year. Negative results of isolation come up to 90% of investigated cases. Only 1.5% of enterovirus isolation attempts finished successfully in 2002 year. The situation when percentage of positive results of isolation is on so low level, the natural alterations in a profile of enterovirus serotype infected population cannot be observed, and serological investigations can be conducted for enterovirus serotypes others than really circulating and causing infections in population.

Antibodies, Viral↗
PubMed2000

Evaluation of enterovirus serological tests IgM-EIA and complement fixation in patients with meningitis, confirmed by detection of enteroviral RNA by RT-PCR in cerebrospinal fluid.

An enzyme immunoassay (EIA) for detection of anti-enterovirus IgM antibodies was compared with complement fixation test in 43 patients with confirmed enterovirus meningitis by RT-PCR of cerebrospinal fluids (CSF). In 34% of patients with enterovirus meningitis, IgM antibodies could be found, whereas complement fixation tests were positive in only 20%. The specificity was determined with sera of 105 patients with non-enterovirus meningitis. Specificity of IgM EIA and of complement fixation was 94% and 85%, respectively. In four patients with meningitis but without enterovirus detection in CSF, RT-PCR and virus isolation from stools were positive. In three of these patients, IgM antibodies were detected, giving a strong indication of an enterovirus-associated disease. Because of the high specificity of IgM EIA, diagnosis of enterovirus-associated diseases can be carried out in a single serum sample, whereas by complement fixation tests, only fourfold increases in antibody titres in paired sera indicate an acute infection. The application of IgM EIA is especially important in cases of meningitis when CSF samples are not available and for diagnosis of enterovirus diseases with other clinical symptoms such as fever, enteritis, and hand-foot-and-mouth disease.

Adolescent↗
PubMed2003

Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study.

Enterovirus infections have been associated with the manifestation of clinical type 1 diabetes in a number of reports, and recent prospective studies have suggested that enterovirus infections may initiate the autoimmune process, leading to the disease. In the present study, we analyzed the role of enterovirus infections in a Finnish birth cohort study, Diabetes Prediction and Prevention (DIPP), in which all newborn infants are screened for diabetes-associated HLA-DQB1 alleles, and those with an increased genetic risk are invited for prospective follow-up. Enterovirus infections were diagnosed by serology and reverse transcriptase-polymerase chain reaction (RT-PCR) from serum samples taken from birth every 3-6 months. Case children included 41 infants who became positive for diabetes-associated autoantibodies during the observation. Control children comprised altogether 196 infants who remained autoantibody negative and were matched for the time of birth, sex, and HLA-DQB1 alleles. Enterovirus infections were more frequent in case children than in control children (P = 0.004), and the average enterovirus antibody levels were also higher in the case children (P = 0.003). Enterovirus infections were particularly frequent during the 6-month period preceding the first detection of autoantibodies: 51% of the case children compared with 28% of the control children had an infection in that time interval (P = 0.003). There was no difference in the frequency of adenovirus infections between the groups (P = 0.9). The present results imply that enterovirus infections are associated with the appearance of beta-cell autoantibodies. A possible causal relationship is supported by the clustering of infections to the time when autoantibodies appeared.

Adenoviridae Infections↗
PubMed2005

Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation.

AIMS/HYPOTHESIS: We have previously observed an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population. The aim of this study was to analyse whether maternal enterovirus antibody status, which reflects both the frequency of enterovirus infections and the protection conferred by the mother on the offspring, also correlates with the incidence of type 1 diabetes. METHODS: Maternal enterovirus antibodies were analysed from serum samples taken from pregnant women between 1983 and 2001 in Finland and Sweden using enzyme immunoassay and neutralisation assays. Comparable samples were also taken between 1999 and 2001 in countries with a lower incidence of diabetes (Estonia, Germany, Hungary, Israel, Lithuania, Russia). RESULTS: A clear decrease was observed in maternal enterovirus antibody levels over the past 20 years (p<0.0001). The frequency of enterovirus antibodies was higher in countries with a low or intermediate incidence of type 1 diabetes compared with high-incidence countries (p<0.0001). CONCLUSIONS/INTERPRETATION: These findings are in line with our previous observations supporting the hypothesis that a low frequency of enterovirus infection in the background population increases the susceptibility of young children to the diabetogenic effect of enteroviruses.

Antibodies, Viral↗
PubMed2006

Combining multiplex reverse transcription-PCR and a diagnostic microarray to detect and differentiate enterovirus 71 and coxsackievirus A16.

Cluster A enteroviruses, including enterovirus 71 (EV71) and coxsackievirus A16 (CA16), are known to cause hand-foot-and-mouth disease (HFMD). Despite the close genetic relationship between these two viruses, EV71 is generally known to be a more perpetuating pathogen involved in severe clinical manifestations and deaths. While the serotyping of enteroviruses is mostly done by conventional immunological methods, many clinical isolates remain unclassifiable due to the limited number of antibodies against enterovirus surface proteins. Array-based assays are able to detect several serotypes with high accuracy. We combined an enterovirus microarray with multiplex reverse transcription-PCR to try to develop a method of sensitively and accurately detecting and differentiating EV71 and CA16. In an effort to design serotype-specific probes for detection of the virus, we first did an elaborate bioinformatic analysis of the sequence database derived from different enterovirus serotypes. We then constructed a microarray using 60-mer degenerate oligonucleotide probes covalently bound to array slides. Using this enterovirus microarray to study 144 clinical specimens from patients infected with HFMD or suspected to have HFMD, we found that it had a diagnostic accuracy of 92.0% for EV71 and 95.8% for CA16. Diagnostic accuracy for other enteroviruses (non-EV71 or -CA16) was 92.0%. All specimens were analyzed in parallel by real-time PCR and subsequently confirmed by neutralization tests. This highly sensitive array-based assay may become a useful alternative in clinical diagnostics of EV71 and CA16.

DNA Probes↗
PubMed1998

Rapid shell vial culture technique for detection of enteroviruses and adenoviruses in fecal specimens: comparison with conventional virus isolation method.

Detection of enteroviruses and adenoviruses mainly in fecal specimens by rapid culture with inoculation onto cell monolayers in flat-bottom tubes by centrifugation and immunofluorescence staining with genus-specific monoclonal antibodies was compared with that by the conventional virus isolation procedure. For both conventional culture and shell vial culture human lung fibroblast cells and tertiary monkey kidney cells were used. For enterovirus detection, 979 clinical specimens (916 stool specimens, 56 cerebrospinal fluid specimens, and 7 nasopharyngeal swabs) were used. Conventional culture detected 74 enterovirus isolates. A cytopathic effect compatible with the presence of an enterovirus after 3 days of incubation occurred in 25 of the 74 (34%) specimens that eventually became positive. The detection rate for enteroviruses by rapid cell culture after 2 to 3 days of incubation was 42 of 74 (57%). The genus-specific enterovirus monoclonal antibody did not react with strains of echovirus types 22 and 23 or enterovirus type 71. Rapid cell culture for the detection of adenoviruses was performed with 567 clinical specimens (536 stool specimens, 25 cerebrospinal fluid specimens, and 6 miscellaneous specimens), in which 42 adenoviruses were found by conventional culture. Nine of the 42 (21%) adenovirus isolates were detected by conventional culture within 3 days after inoculation, whereas 21 (50%) were found by rapid cell culture within 2 to 3 days. Only two of the nine specimens found to be positive for the enteric adenovirus type 41 by conventional culture as well by a type-specific enzyme-linked immunosorbent assay (ELISA) tested positive by rapid cell culture. In conclusion, the rapid shell vial assay allows the early detection and identification of enteroviruses and adenoviruses in clinical specimens but is markedly less sensitive than the conventional isolation procedure according to the eventual results of the conventional isolation procedure. Conventional cell culture remains a prerequisite for serotyping of enteroviral isolates. On the basis of the results for adenovirus type 41, the rapid detection of adenoviruses was not considered to be useful for the detection of clinically relevant adenoviruses in fecal samples.

Adenoviruses, Human↗
PubMed1999

Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification.

Sixty-six human enterovirus serotypes have been identified by serum neutralization, but the molecular determinants of the serotypes are unknown. Since the picornavirus VP1 protein contains a number of neutralization domains, we hypothesized that the VP1 sequence should correspond with neutralization (serotype) and, hence, with phylogenetic lineage. To test this hypothesis and to analyze the phylogenetic relationships among the human enteroviruses, we determined the complete VP1 sequences of the prototype strains of 47 human enterovirus serotypes and 10 antigenic variants. Our sequences, together with those available from GenBank, comprise a database of complete VP1 sequences for all 66 human enterovirus serotypes plus additional strains of seven serotypes. Phylogenetic trees constructed from complete VP1 sequences produced the same four major clusters as published trees based on partial VP2 sequences; in contrast to the VP2 trees, however, in the VP1 trees strains of the same serotype were always monophyletic. In pairwise comparisons of complete VP1 sequences, enteroviruses of the same serotype were clearly distinguished from those of heterologous serotypes, and the limits of intraserotypic divergence appeared to be about 25% nucleotide sequence difference or 12% amino acid sequence difference. Pairwise comparisons suggested that coxsackie A11 and A15 viruses should be classified as strains of the same serotype, as should coxsackie A13 and A18 viruses. Pairwise identity scores also distinguished between enteroviruses of different clusters and enteroviruses from picornaviruses of different genera. The data suggest that VP1 sequence comparisons may be valuable in enterovirus typing and in picornavirus taxonomy by assisting in the genus assignment of unclassified picornaviruses.

Amino Acid Sequence↗
PubMed2003

Recombination in circulating enteroviruses.

Recombination is a well-known phenomenon for enteroviruses. However, the actual extent of recombination in circulating nonpoliovirus enteroviruses is not known. We have analyzed the phylogenetic relationships in four genome regions, VP1, 2A, 3D, and the 5' nontranslated region (NTR), of 40 enterovirus B strains (coxsackie B viruses and echoviruses) representing 11 serotypes and isolated in 1981 to 2002 in the former Soviet Union states. In the VP1 region, strains of the same serotype expectedly grouped with their prototype strain. However, as early as the 2A region, phylogenetic grouping differed significantly from that in the VP1 region and indicated recombination within the 2A region. Moreover, in the 5' NTR and 3D region, only 1 strain of 40 grouped with its prototype strain. Instead, we observed a major group in both the 5' NTR and the 3D region that united most (in the 5' NTR) or all (in the 3D region) of the strains studied, regardless of the serotype. Subdivision within that major group in the 3D region correlated with the time of virus isolation but not with the serotype. Therefore, we conclude that a majority, if not all, circulating enterovirus B strains are recombinants relative to the prototype strains, isolated mostly in the 1950s. Moreover, the ubiquitous recombination has allowed different regions of the enterovirus genome to evolve independently. Thus, a novel model of enterovirus genetics is proposed: the enterovirus genome is a stable symbiosis of genes, and enterovirus species consist of a finite set of capsid genes responsible for different serotypes and a continuum of nonstructural protein genes that seem to evolve in a relatively independent manner.

5' Untranslated Regions↗
PubMed2001

Detection and rapid differentiation of human enteroviruses in water sources by restriction enzyme analysis.

The objective of this study was to assess the application and efficiency of molecular techniques for the detection and serotyping of enteroviruses from environmental water samples. Samples of water were collected at regular intervals upstream and downstream of an informal settlement. Techniques for the detection of enteroviruses included a reverse transcription polymerase chain reaction (RT-PCR), nested PCR (n-PCR) and Sabin-specific triplex PCR. A specific 297 bp fragment was amplified by the n-PCR and subjected to restriction enzyme (RE) analysis to differentiate between various serotypes of prototypical enteroviruses. Enteroviruses that gave inconclusive restriction patterns were typed by partial sequencing of the VP1 region. Results indicated a high incidence of enteroviruses, predominantly coxsackie B viruses. The results on polioviruses, as well as other enteroviruses, contributed valuable information on enteroviruses circulating in the community. The molecular approach described here proved suitable for the rapid, sensitive, specific and cost effective, simultaneous detection and typing of enteroviruses in water.

Costs and Cost Analysis↗
PubMed2002

Enterovirus infections and type 1 diabetes.

Type 1 (insulin-dependent) diabetes is a typical organ-specific autoimmune disease where insulin-producing beta cells are destroyed by immune mediated mechanisms. The risk of the disease is modulated by genetic factors, mainly genes coding for human leukocyte antigens (HLA), but environmental factors are needed to trigger the process in genetically susceptible individuals. Possible viral triggers of the disease have been sought for years but their identification has been very difficult. Recently, considerable progress has been made by employing new research methods which have supported the idea that the group of enteroviruses may be particularly important in the pathogenesis. An association between enterovirus infections and type 1 diabetes was first reported 30 years ago and since then evaluated in several studies. Recent molecular studies have considerably strengthened this hypothesis by showing that enterovirus genome is present in the blood of diabetic patients. In addition, the first prospective studies have suggested that enterovirus infections may initiate the beta-cell damaging process several years before clinical diabetes is diagnosed. Ecological studies have also indicated similarities in the epidemiology of type 1 diabetes and poliomyelitis - a well-known enterovirus disease. Experimental models, like enterovirus-infected mice or in vitro-cultured beta cells, have provided important information about possible mechanisms, but still it is not known how beta cells are destroyed in human beings. The ongoing prospective studies will answer many open questions, and should the association still hold true, intervention trials will be needed to confirm causality. Even if enterovirus infections were not associated with all diabetes cases but rather with a subgroup of them, this would offer attractive possibilities to prevent the disease or part of it, for example, by an enterovirus vaccine.

Animals↗
PubMed2003

Determination of enterovirus serotype inferred from sequence analysis of PCR products.

BACKGROUND: Enterovirus infections are common in neonates. Virus isolation is the only diagnostic method to confirm enterovirus serotype infections, however, is not always successful. OBJECTIVES: A new approach for the diagnosis of enterovirus infections was performed, using the reference strain inferred from sequence analysis of PCR products. STUDY DESIGN: Virus isolation, enterovirus RT-PCR and sequence analysis were performed from clinical samples or stored sera from two neonates with fever and rash. Neutralizing test (NT) antibodies against prototype reference virus were measured in paired sera. RESULTS: Virus isolation was negative in both patients but the enterovirus genome was amplified in the acute phase sera obtained from the two patients. From the results of sequence analysis of 109 nucleotides located in the 5'-noncoding of the conserved region of enteroviruses, a high homology to echovirus types 25 and 30 was found. More than a 4-fold increase in NT antibodies against reference viruses was demonstrated in the acute and convalescent phase sera. They were confirmed as echovirus type 25 and 30 infection, respectively. CONCLUSIONS: These virological examinations are practical and useful for clinical settings for a diagnosis of enterovirus infections because of an insufficient positive rate in virus isolation.

Adult↗
PubMed1993

[A survey on enteroviruses-carrying status among healthy population in Changle and Wucheng counties of Shandong Province. Shandong Collaborative Group of Poliomyelitis].

Four-hundred and fourty-six faecal specimens sampled from healthy carriers between 0 and more than 20 year-old age groups in Changle and Wucheng counties of Shandong Province were collected from June to Sept. of 1991. From them, 142 (31.84%) isolates of enteroviruses were obtained. There was no significant difference in the enteroviruses isolation rate between Changle and Wucheng. No poliovirus was isolated. Among other enterovirus isolates, 85 were echoviruses, 6 coxsackieviruses, 9 enterovirus type 70 and 2 enterovirus type 71. Other 40 isolates were positive for cytopathogenic effect (CPE) in cell culture, but they could not be identified by antisera to poliovirus and enteroviruses. The results showed that the infection by non-polio enteroviruses which could cause polio-like paralysis should be paid attention in the poliomyelitis eradication program.

Adolescent↗
PubMed2004

Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan.

CONTEXT: Although enterovirus 71 has caused epidemics associated with significant morbidity and mortality, its transmission has not been thoroughly investigated. OBJECTIVES: To investigate enterovirus 71 transmission and determine clinical outcomes within households. DESIGN, SETTING, AND PARTICIPANTS: Prospective family cohort study to investigate patients at a children's hospital in Taiwan and family members of these patients who had signs and symptoms suggestive of enterovirus 71 between February 2001 and August 2002. Patients and household members underwent clinical evaluations, virological studies, questionnaire-based interviews, and were followed up for 6 months. MAIN OUTCOME MEASURES: Enterovirus 71 infection, defined as a positive viral culture from a throat or rectal swab, or the presence of IgM or a 4-fold increase in neutralizing antibody in serum; and clinical syndromes, defined as asymptomatic; uncomplicated symptomatic; and complicated; with unfavorable outcomes of sequelae or death. RESULTS: Ninety-four families (433 family members) had at least 1 family member with evidence of enterovirus 71 infection. The overall enterovirus 71 transmission rate to household contacts was 52% (176/339 household contacts). Transmission rates were 84% for siblings (70/83); 83%, cousins (19/23); 41%, parents (72/175); 28%, grandparents (10/36); and 26%, uncles and aunts (5/19). Of 183 infected children, 11 (6%) were asymptomatic and 133 (73%) had uncomplicated illnesses (hand, foot, and mouth disease, herpangina, nonspecific febrile illness, upper respiratory tract infection, enteritis, or viral exanthema). Twenty-one percent (39/183) experienced complicated syndromes including the central nervous system or cardiopulmonary failure. During the 6-month follow-up, 10 died and 13 had long-term sequelae consisting of dysfunction in swallowing, cranial nerve palsies, central hypoventilation, or limb weakness and atrophy. Age younger than 3 years was the most significant factor associated with an unfavorable outcome in children (P =.004). Among 87 infected adults, 46 (53%) were asymptomatic, 34 (39%) had nonspecific illnesses of fever, sore throat, or gastrointestinal discomfort, and 7 (8%) had hand, foot, and mouth disease. There were no complicated cases in adults. CONCLUSIONS: Enterovirus 71 household transmission rates were high for children in Taiwan and severe disease with serious complications, sequelae, and death occurred frequently. In contrast, adults had a much lower rate of acquisition of the infection and much less adverse sequelae.

Adolescent↗
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↗