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Heikki Hyöty - One of the best experts on this subject based on the ideXlab platform.
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Maternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring
Diabetes Care, 2012Co-Authors: Hanna Viskari, Mikael Knip, Jorma Ilonen, Sisko Tauriainen, Heljä-marja Surcel, Heini Huhtala, Riitta Veijola, Olli Simell, Heikki HyötyAbstract:OBJECTIVE Maternal Enterovirus infections during pregnancy have been linked to an increased risk of type 1 diabetes in the offspring. The aim of this study was to evaluate this association in a unique series of pregnant mothers whose child progressed to clinical type 1 diabetes. RESEARCH DESIGN AND METHODS Maternal and in utero Enterovirus infections were studied in 171 offspring who presented with type 1 diabetes before the age of 11 years and in 316 control subjects matched for date and place of birth, gender, and HLA-DQ risk alleles for diabetes. Acute Enterovirus infections were diagnosed by increases in Enterovirus IgG and IgM in samples taken from the mother at the end of the first trimester of pregnancy and cord blood samples taken at delivery. RESULTS Signs of maternal Enterovirus infection were observed in altogether 19.3% of the mothers of affected children and in 12.0% of the mothers of control children ( P = 0.038). This difference was seen in different HLA risk groups and in both genders of the offspring, and it was unrelated to the age of the child at the diagnosis of diabetes or the age of the mother at delivery. CONCLUSIONS These results suggest that an Enterovirus infection during pregnancy is not a major risk factor for type 1 diabetes in childhood but may play a role in some susceptible subjects.
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type 1 diabetes is associated with Enterovirus infection in gut mucosa
Diabetes, 2012Co-Authors: Maarit Oikarinen, Teemu Honkanen, Pekka Collin, Immo Rantala, Markku Maki, Katri Kaukinen, Sisko Tauriainen, Sami Oikarinen, Heikki HyötyAbstract:Enterovirus infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for Enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of Enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent Enterovirus infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes.
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Enterovirus rna in blood is linked to the development of type 1 diabetes
Diabetes, 2011Co-Authors: Sami Oikarinen, Mikael Knip, Jorma Ilonen, Sisko Tauriainen, Heini Huhtala, Riitta Veijola, Olli Simell, Mika Martiskainen, Heikki HyötyAbstract:OBJECTIVE To assess whether the detection of Enterovirus RNA in blood predicts the development of clinical type 1 diabetes in a prospective birth cohort study. Further, to study the role of Enteroviruses in both the initiation of the process and the progression to type 1 diabetes. RESEARCH DESIGN AND METHODS This was a nested case-control study where all case children ( N = 38) have progressed to clinical type 1 diabetes. Nondiabetic control children ( N = 140) were pairwise matched for sex, date of birth, hospital district, and HLA-DQ–conferred genetic susceptibility to type 1 diabetes. Serum samples, drawn at 3- to 12-month intervals, were screened for Enterovirus RNA using RT-PCR. RESULTS Enterovirus RNA–positive samples were more frequent among the case subjects than among the control subjects. A total of 5.1% of the samples (17 of 333) in the case group were Enterovirus RNA–positive compared with 1.9% of the samples (19 of 993) in the control group ( P < 0.01). The strongest risk for type 1 diabetes was related to Enterovirus RNA positivity during the 6-month period preceding the first autoantibody-positive sample (odds ratio 7.7 [95% CI 1.9–31.5]). This risk effect was stronger in boys than in girls. CONCLUSIONS The present study supports the hypothesis that Enteroviruses play a role in the pathogenesis of type 1 diabetes, especially in the initiation of the β-cell damaging process. The Enterovirus-associated risk for type 1 diabetes may be stronger in boys than in girls.
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maternal Enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age
Experimental Diabetes Research, 2008Co-Authors: Maria Elfving, Sami Oikarinen, Johan Svensson, Bjorn Jonsson, Per E Olofsson, Goran Sundkvist, Bengt Lindberg, Ake Lernmark, Heikki HyötyAbstract:Maternal Enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational Enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for Enterovirus-specific immunoglobulin M (IgM) antibodies and Enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were Enterovirus IgM-positive, and none was positive for Enterovirus RNA. In the control group, 14/90 (16%) were Enterovirus IgM-positive, and 4/90 (4%) were positive for Enterovirus RNA (n.s.). Boys of Enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22-17.6), as compared to boys of IgM-negative mothers (P < .025). These results suggest that gestational Enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.
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detection of Enteroviruses in the intestine of type 1 diabetic patients
Clinical and Experimental Immunology, 2007Co-Authors: Maarit Oikarinen, Teemu Honkanen, Immo Rantala, Markku Maki, Katri Kaukinen, Kristiina Vuori, Sisko Tauriainen, Sami Oikarinen, Heikki HyötyAbstract:Enterovirus infections have been diagnosed more frequently in type 1 diabetic patients than in the healthy population, and Enteroviruses have also been found in the pancreas of diabetic patients. Primary replication of the virus occurs in the gut, but there are no previous studies evaluating possible presence of virus in the intestine of diabetic patients. The purpose of this study was to investigate if Enteroviruses can be found in small intestinal tissue of type 1 diabetic patients. Formalin-fixed, paraffin-embedded upper intestinal biopsy samples were analysed for the presence of Enterovirus using in situ hybridization and immunohistochemistry. Enterovirus was detected by in situ hybridization in six (50%) of the type 1 diabetic patients (n = 12) but in none of the control subjects (n = 10, P = 0·015). Immunohistochemistry identified Enterovirus in nine (75%) of the patients and one (10%) control subject (P = 0·004). The presence of the virus was confirmed by reverse transcription–polymerase chain reaction in one of the four patients from whom a frozen and unfixed sample was available. Intestinal morphology was normal in all study subjects. The results suggest that a substantial proportion of type 1 diabetic patients have an ongoing Enterovirus infection in gut mucosa, possibly reflecting persistent Enterovirus infection. This observation opens new avenues for further studies on the possible role of Enteroviruses in human type 1 diabetes.
Kevin Messacar - One of the best experts on this subject based on the ideXlab platform.
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Enterovirus d68 and acute flaccid myelitis evaluating the evidence for causality
Lancet Infectious Diseases, 2018Co-Authors: Kevin Messacar, Edwin J Asturias, Alison M Hixon, Coretta Van Leerbuter, H G M Niesters, Kenneth L Tyler, Mark J AbzugAbstract:Summary Increased circulation of Enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon condition of paralysis due to lesions in the anterior horn of the spinal cord. The identification of Enterovirus D68 in respiratory specimens from cases of acute flaccid myelitis worldwide further supports an association, yet the absence of direct virus isolation from affected tissues, infrequent detection in cerebrospinal fluid, and the absence, until recently, of an animal model has left the causal nature of the relationship unproven. In this Personal View we evaluate epidemiological and biological evidence linking Enterovirus D68 and acute flaccid myelitis. We applied the Bradford Hill criteria to investigate the evidence for a causal relationship and highlight the importance of comprehensive surveillance and research to further characterise the role of Enterovirus D68 in acute flaccid myelitis and pursue effective therapies and prevention strategies.
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a novel outbreak Enterovirus d68 strain associated with acute flaccid myelitis cases in the usa 2012 14 a retrospective cohort study
Lancet Infectious Diseases, 2015Co-Authors: Alexander L Greninger, Kevin Messacar, Samia N Naccache, Anna Clayton, Guixia Yu, Sneha Somasekar, Scot Federman, Doug Stryke, Christopher D Anderson, Shigeo YagiAbstract:Summary Background Enterovirus D68 was implicated in a widespread outbreak of severe respiratory illness across the USA in 2014 and has also been reported sporadically in patients with acute flaccid myelitis. We aimed to investigate the association between Enterovirus D68 infection and acute flaccid myelitis during the 2014 Enterovirus D68 respiratory outbreak in the USA. Methods Patients with acute flaccid myelitis who presented to two hospitals in Colorado and California, USA, between Nov 24, 2013, and Oct 11, 2014, were included in the study. Additional cases identified from Jan 1, 2012, to Oct 4, 2014, via statewide surveillance were provided by the California Department of Public Health. We investigated the cause of these cases by metagenomic next-generation sequencing, viral genome recovery, and Enterovirus D68 phylogenetic analysis. We compared patients with acute flaccid myelitis who were positive for Enterovirus D68 with those with acute flaccid myelitis but negative for Enterovirus D68 using the two-tailed Fisher's exact test, two-sample unpaired t test, and Mann-Whitney U test. Findings 48 patients were included: 25 with acute flaccid myelitis, two with Enterovirus-associated encephalitis, five with Enterovirus-D68-associated upper respiratory illness, and 16 with aseptic meningitis or encephalitis who tested positive for Enterovirus. Enterovirus D68 was detected in respiratory secretions from seven (64%) of 11 patients comprising two temporally and geographically linked acute flaccid myelitis clusters at the height of the 2014 outbreak, and from 12 (48%) of 25 patients with acute flaccid myelitis overall. Phylogenetic analysis revealed that all Enterovirus D68 sequences associated with acute flaccid myelitis grouped into a clade B1 strain that emerged in 2010. Of six coding polymorphisms in the clade B1 Enterovirus D68 polyprotein, five were present in neuropathogenic poliovirus or Enterovirus D70, or both. One child with acute flaccid myelitis and a sibling with only upper respiratory illness were both infected by identical Enterovirus D68 strains. Enterovirus D68 viraemia was identified in a child experiencing acute neurological progression of his paralytic illness. Deep metagenomic sequencing of cerebrospinal fluid from 14 patients with acute flaccid myelitis did not reveal evidence of an alternative infectious cause to Enterovirus D68. Interpretation These findings strengthen the putative association between Enterovirus D68 and acute flaccid myelitis and the contention that acute flaccid myelitis is a rare yet severe clinical manifestation of Enterovirus D68 infection in susceptible hosts. Funding National Institutes of Health, University of California, Abbott Laboratories, and the Centers for Disease Control and Prevention.
A H Mertens - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a rapid real time rt pcr assay for detection of Enterovirus rna in cerebrospinal fluid specimens
Journal of Clinical Virology, 2002Co-Authors: W A Verstrepen, P Bruynseels, A H MertensAbstract:Abstract Background: We previously described the characteristics of a single-tube real-time Enterovirus reverse transcriptase polymerase chain reaction (RT-PCR) assay based on a fluorogenic probe and primers directed to highly conserved sequences in the 5′-untranslated region (UTR) of the Enterovirus genome. Objectives: To evaluate the performance of the assay on a larger number of cerebrospinal fluid (CSF) specimens from patients suspected of having viral meningitis. Study design: Real-time Enterovirus RT-PCR and viral culture were performed on CSF specimens received from March 2000 to November 2001. Patient records were retrospectively reviewed for final clinical diagnosis. Results: From the 186 CSF specimens tested, culture was positive for Enterovirus in 31 cases, whereas real-time RT-PCR detected Enterovirus RNA in 45 CSF specimens. The sensitivity of real-time RT-PCR in relation to the clinical diagnosis of viral meningitis was 72.6%, whereas the sensitivity of viral culture reached only 57.4%. Enterovirus RNA was also found in a number of specimens with low leukocyte counts. Conclusions: We confirm that the real-time Enterovirus RT-PCR assay for CSF specimens is significantly more sensitive than viral culture.
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rapid detection of Enterovirus rna in cerebrospinal fluid specimens with a novel single tube real time reverse transcription pcr assay
Journal of Clinical Microbiology, 2001Co-Authors: W A Verstrepen, Sofie Kuhn, Mark M Kockx, Martine Van De Vyvere, A H MertensAbstract:A single-tube real-time reverse transcription-PCR (RT-PCR) assay for Enterovirus detection in cerebrospinal fluid (CSF) was developed based on a fluorogenic probe and primers directed to highly conserved sequences in the 5′ untranslated region of the Enterovirus genome. Quantitative detection of Enterovirus genome was demonstrated in a linear range spanning at least 5 logs. Endpoint titration experiments revealed that the in-tube detection limit of the assay was 11.8 Enterovirus genome equivalents (95% detection rate) corresponding in our current extraction protocol to 592 Enterovirus genome equivalents per ml of CSF. Twenty CSF specimens not suspected of viral meningitis were all found to be negative, and no cross-reactivity with herpes simplex virus type 1 and type 2, varicella-zoster virus, rhinovirus type 53, and influenza viruses A and B was observed. Nineteen CSF specimens from 70 patients suspected of viral meningitis were determined to be positive by PCR (27.1%), whereas only 17 were found to be positive by viral culture (24.3%). The sensitivity of the assay was 100% and the specificity was 96.2% compared to viral culture. Data from the real-time RT-PCR assay were available within 4 h. Our data suggest that the novel real-time RT-PCR assay may offer a reliable but significantly faster alternative to viral culture. Owing to the elimination of postamplification detection steps, its conduct required considerably less hands-on time and was associated with a substantially reduced carryover risk compared to previously described PCR-based Enterovirus detection assays.
Kenneth J. Mutton - One of the best experts on this subject based on the ideXlab platform.
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development and evaluation of a real time rt pcr for the detection of Enterovirus and parechovirus rna in csf and throat swab samples
Journal of Medical Virology, 2002Co-Authors: Caroline E. Corless, Raymond Borrow, Andrew J. Fox, Edward B. Kaczmarski, Malcolm Guiver, Valerie Edwardsjones, Kenneth J. MuttonAbstract:A two-step reverse transcriptase TaqMan™ duplex PCR (RT-PCR) assay was developed using the ABI 7700 Sequence Detection System for the detection of Enterovirus (EV) and parechovirus type 1 and 2 (PEV) RNA from samples of cerebrospinal fluid (CSF) and throat swabs. Using sequence-specific fluorescent dye labeled probes and continuous real-time monitoring, PCR amplified product accumulation was measured. Based on limiting dilutions, the TaqMan™ Enterovirus and parechovirus RT-PCR showed an increase of two orders of magnitude compared to cell culture with sensitivity of 100% (7/7) when assessed using Enterovirus cell culture positive samples (CSF, TS). The assays were specific for Enterovirus and parechovirus and did not amplify a wide selection of virus and bacterial isolates. RNA was amplified from 22 Enterovirus serotypes: coxsackie A7, A9, A21; coxsackie B2, B3, B4, B5; echovirus 2, 4, 6, 7, 9, 11, 13, 17, 18, 19, 30, 31; poliovirus types 1, 2, and 3, and parechovirus types 1 and 2. The assay was used to assess the incidence of Enterovirus and parechovirus RNA in cell culture negative CSF and throat swab samples (n = 200). An additional 33 (15.9%) Enterovirus and 2 (1%) parechovirus were identified as positive by RT-PCR. Also, of 100 CSF samples from suspected cases of meningococcal meningitis submitted for meningococcal PCR testing, 59 (59%) were Enterovirus and 2 (2%) parechovirus 1 and 2 were positive by RT-PCR. The TaqManTM duplex assay offers a more rapid and sensitive alternative to conventional cell culture for the diagnosis of Enterovirus and parechovirus infection. Closed tube real-time detection using the ABI Sequence Detection System obviates the need for post-PCR manipulation, which reduces hands on time and eliminates the risk of contamination from amplified PCR product. J. Med. Virol. 67:555-562, 2002. © 2002 Wiley-Liss, Inc.
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Development and evaluation of a 'real-time' RT-PCR for the detection of Enterovirus and parechovirus RNA in CSF and throat swab samples
Journal of Medical Virology, 2002Co-Authors: Caroline E. Corless, Raymond Borrow, Andrew J. Fox, Valerie Edwards-jones, Edward B. Kaczmarski, Malcolm Guiver, Kenneth J. MuttonAbstract:A two-step reverse transcriptase TaqMantrade mark duplex PCR (RT-PCR) assay was developed using the ABI 7700 Sequence Detection System for the detection of Enterovirus (EV) and parechovirus type 1 and 2 (PEV) RNA from samples of cerebrospinal fluid (CSF) and throat swabs. Using sequence-specific fluorescent dye labeled probes and continuous 'real-time' monitoring, PCR amplified product accumulation was measured. Based on limiting dilutions, the TaqMantrade mark Enterovirus and parechovirus RT-PCR showed an increase of two orders of magnitude compared to cell culture with sensitivity of 100% (7/7) when assessed using Enterovirus cell culture positive samples (CSF, TS). The assays were specific for Enterovirus and parechovirus and did not amplify a wide selection of virus and bacterial isolates. RNA was amplified from 22 Enterovirus serotypes: coxsackie A7, A9, A21; coxsackie B2, B3, B4, B5; echovirus 2, 4, 6, 7, 9, 11, 13, 17, 18, 19, 30, 31; poliovirus types 1, 2, and 3, and parechovirus types 1 and 2. The assay was used to assess the incidence of Enterovirus and parechovirus RNA in cell culture negative CSF and throat swab samples (n = 200). An additional 33 (15.9%) Enterovirus and 2 (1%) parechovirus were identified as positive by RT-PCR. Also, of 100 CSF samples from suspected cases of meningococcal meningitis submitted for meningococcal PCR testing, 59 (59%) were Enterovirus and 2 (2%) parechovirus 1 and 2 were positive by RT-PCR. The TaqMantrade mark duplex assay offers a more rapid and sensitive alternative to conventional cell culture for the diagnosis of Enterovirus and parechovirus infection. Closed tube real-time detection using the ABI Sequence Detection System obviates the need for post-PCR manipulation, which reduces hands on time and eliminates the risk of contamination from amplified PCR product.
Sami Oikarinen - One of the best experts on this subject based on the ideXlab platform.
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type 1 diabetes is associated with Enterovirus infection in gut mucosa
Diabetes, 2012Co-Authors: Maarit Oikarinen, Teemu Honkanen, Pekka Collin, Immo Rantala, Markku Maki, Katri Kaukinen, Sisko Tauriainen, Sami Oikarinen, Heikki HyötyAbstract:Enterovirus infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for Enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of Enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent Enterovirus infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes.
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Enterovirus rna in blood is linked to the development of type 1 diabetes
Diabetes, 2011Co-Authors: Sami Oikarinen, Mikael Knip, Jorma Ilonen, Sisko Tauriainen, Heini Huhtala, Riitta Veijola, Olli Simell, Mika Martiskainen, Heikki HyötyAbstract:OBJECTIVE To assess whether the detection of Enterovirus RNA in blood predicts the development of clinical type 1 diabetes in a prospective birth cohort study. Further, to study the role of Enteroviruses in both the initiation of the process and the progression to type 1 diabetes. RESEARCH DESIGN AND METHODS This was a nested case-control study where all case children ( N = 38) have progressed to clinical type 1 diabetes. Nondiabetic control children ( N = 140) were pairwise matched for sex, date of birth, hospital district, and HLA-DQ–conferred genetic susceptibility to type 1 diabetes. Serum samples, drawn at 3- to 12-month intervals, were screened for Enterovirus RNA using RT-PCR. RESULTS Enterovirus RNA–positive samples were more frequent among the case subjects than among the control subjects. A total of 5.1% of the samples (17 of 333) in the case group were Enterovirus RNA–positive compared with 1.9% of the samples (19 of 993) in the control group ( P < 0.01). The strongest risk for type 1 diabetes was related to Enterovirus RNA positivity during the 6-month period preceding the first autoantibody-positive sample (odds ratio 7.7 [95% CI 1.9–31.5]). This risk effect was stronger in boys than in girls. CONCLUSIONS The present study supports the hypothesis that Enteroviruses play a role in the pathogenesis of type 1 diabetes, especially in the initiation of the β-cell damaging process. The Enterovirus-associated risk for type 1 diabetes may be stronger in boys than in girls.
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maternal Enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age
Experimental Diabetes Research, 2008Co-Authors: Maria Elfving, Sami Oikarinen, Johan Svensson, Bjorn Jonsson, Per E Olofsson, Goran Sundkvist, Bengt Lindberg, Ake Lernmark, Heikki HyötyAbstract:Maternal Enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational Enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for Enterovirus-specific immunoglobulin M (IgM) antibodies and Enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were Enterovirus IgM-positive, and none was positive for Enterovirus RNA. In the control group, 14/90 (16%) were Enterovirus IgM-positive, and 4/90 (4%) were positive for Enterovirus RNA (n.s.). Boys of Enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22-17.6), as compared to boys of IgM-negative mothers (P < .025). These results suggest that gestational Enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.
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detection of Enteroviruses in the intestine of type 1 diabetic patients
Clinical and Experimental Immunology, 2007Co-Authors: Maarit Oikarinen, Teemu Honkanen, Immo Rantala, Markku Maki, Katri Kaukinen, Kristiina Vuori, Sisko Tauriainen, Sami Oikarinen, Heikki HyötyAbstract:Enterovirus infections have been diagnosed more frequently in type 1 diabetic patients than in the healthy population, and Enteroviruses have also been found in the pancreas of diabetic patients. Primary replication of the virus occurs in the gut, but there are no previous studies evaluating possible presence of virus in the intestine of diabetic patients. The purpose of this study was to investigate if Enteroviruses can be found in small intestinal tissue of type 1 diabetic patients. Formalin-fixed, paraffin-embedded upper intestinal biopsy samples were analysed for the presence of Enterovirus using in situ hybridization and immunohistochemistry. Enterovirus was detected by in situ hybridization in six (50%) of the type 1 diabetic patients (n = 12) but in none of the control subjects (n = 10, P = 0·015). Immunohistochemistry identified Enterovirus in nine (75%) of the patients and one (10%) control subject (P = 0·004). The presence of the virus was confirmed by reverse transcription–polymerase chain reaction in one of the four patients from whom a frozen and unfixed sample was available. Intestinal morphology was normal in all study subjects. The results suggest that a substantial proportion of type 1 diabetic patients have an ongoing Enterovirus infection in gut mucosa, possibly reflecting persistent Enterovirus infection. This observation opens new avenues for further studies on the possible role of Enteroviruses in human type 1 diabetes.