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  • 1.
    Bucardo, Filemon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Kindberg, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Paniagua, Margarita
    Department of Microbiology, University of León, Nicaragua.
    Vildevall, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Genetic susceptibility to symptomatic norovirus infection in Nicaragua2009In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 81, no 4, p. 728-735Article in journal (Refereed)
    Abstract [en]

    Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.

  • 2.
    Davydova, B.
    et al.
    Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland.
    Harkonen, T.
    Härkönen, T., Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland.
    Kaialainen, S.
    Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland.
    Hovi, T.
    Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Roivainen, M.
    Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland.
    Coxsackievirus immunization delays onset of diabetes in non-obese diabetic mice2003In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 69, no 4, p. 510-520Article in journal (Refereed)
    Abstract [en]

    Enteroviruses may be involved in the pathogenesis of Type 1 diabetes through different mechanisms including triggering of autoimmunity. The effect of immunization with coxsackievirus B4-E2 on diabetes incidence was studied in the non-obese diabetic mice, an animal model for human autoimmune insulin-dependent diabetes mellitus. The immunization delayed the onset of diabetes in the mice, and the effect was mediated at least partially by virus immunization-activated splenocytes as demonstrated by adoptive transfer experiments. Immunization resulted in a strong humoral immune response against the immunizing virus, formalin-inactivated coxsackievirus B4-E2. Cell-mediated immune responseto virus antigen was characterised by interferon gamma and interleukin 10 secretion. The immunization also resulted in increased antibody levels against several beta-cell autoantigens. By using epitope mapping we were able to show that in addition to reactivity with the known epitopes of viral proteins and tyrosine phosphatase A-2 or heat shock protein 60, responses to some other regions of autoantigens were enhanced. In preproinsulin, the response was restricted against an antigenic region earlier identified as DR4-dependent epitope. This reactivity can not be explained by homologous amino acid sequences and it is possible that enterovirus immunization might change the autoantigen specific TH1/TH2 balance in non-obese diabetic mice. In conclusion, our results suggest that coxsackievirus immunization increased humoral immune response to beta cell autoantigens and this was associated with a less destructive pathology for spontaneous diabetes in non-obese diabetic mice. © 2003 Wiley-Liss, Inc.

  • 3.
    Esteves, Aida
    et al.
    NOVA University of Lisbon, Portugal.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Pereira, Joana
    NOVA University of Lisbon, Portugal.
    Fortes, Filomeno
    National Institute Public Heatlh, Angola.
    Dimbu, Rafael
    National Institute Public Heatlh, Angola.
    Saraiva, Nilton
    National Institute Public Heatlh, Angola.
    Mendes, Cristina
    NOVA University of Lisbon, Portugal.
    Istrate, Claudia
    NOVA University of Lisbon, Portugal.
    Molecular Epidemiology of Rotavirus in Four Provinces of Angola Before Vaccine Introduction2016In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 88, no 9, p. 1511-1520Article in journal (Refereed)
    Abstract [en]

    Angola is a sub-Saharan country in southern Africa highly affected by diarrhoeal disease with limited epidemiological data regarding etiologic agents. This study was performed during 2012-2013, prior to rotavirus vaccine introduction, with the objective to detect and characterize the rotavirus strains circulating in four provinces of the country: Huambo, Luanda, Zaire, and Cabinda. A high rotavirus detection rate (35%, 117/334) was observed. G1 was the most common G-genotype (83.6%), whereas P[8] (50.9%) followed by P[6] (38.8%) were the most common P-types. G1P[8] was identified as the predominant combination (50%), followed by the unusual G1P[6] (29.3%). Strains such G2P[4], G8P[6], G9P[6], and G12P[6] were also found in lower frequencies (5.2-1.7%). The P[6] strains did not cluster in the phylogenetic trees according to their geographic origin or even the corresponding G-genotype, suggesting a limited number of recent introductions and extensive reassortment events. Our results represent the first report on rotavirus genotype profiles in Angola, showing a wide circulation of the unusual genotype G1P[6], and underline the importance of RV surveillance after the vaccine introduction. (C) 2016 Wiley Periodicals, Inc.

  • 4.
    Gupta, Shipra
    et al.
    Jamia Hamdard, India.
    Krishnan, Anuja
    Jamia Hamdard, India.
    Sharma, Sumit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kumar, Praveen
    Kalawati Saran Childrens Hospital, India.
    Aneja, Satinder
    Kalawati Saran Childrens Hospital, India.
    Ray, Pratima
    Jamia Hamdard, India.
    Changing pattern of prevalence, genetic diversity, and mixed infections of viruses associated with acute gastroenteritis in pediatric patients in New Delhi, India2018In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 90, no 3, p. 469-476Article in journal (Refereed)
    Abstract [en]

    There are very few studies that have assessed multiple viral agents causing Acute-Gastroenteritis (AGE) in India. The present study compared the changing pattern of prevalence and genetic diversity of five enteric viruses associated with acute-diarrhea in Delhi children within a gap of 5 years. Fecal samples were collected from diarrheal children (amp;lt;4 years) during two winter seasons: year 2009-2010 (n=59) and year 2014-2015 (n=85). Samples were individually tested for rotavirus-A, norovirus, astrovirus, adenovirus, and sapovirus using EIA/RT-PCR and genetically characterized by phylogenetic analysis. Rotavirus was the most predominant (54.9%) virus followed by norovirus (25.7%), astrovirus (8.3%), and adenovirus (4.9%) with rare detection of sapovirus (0.7%). While detection rate increased for both rotavirus (49.2-58.8%) and astrovirus (5.1-10.6%), norovirus detection rate decreased (30.5-22.4%) from 2009 to 2015. During the same time period, adenovirus detection remained low (4.7-5.1%). Interestingly, mixed infections increased from 8.5% to 16.5% after 5 years. G1P[8] rotavirus strain was found most predominant (40%). Both type-1 and 8 astroviruses were detected. Single sapovirus detected was of genotype GII.1. Both GI (GI.5, GI.3) and GII (GII.1, GII.4, GII.7, GII.21, GII.13) genogroups of norovirus were detected. Of particular significance was the first detection of other NoV genotypes (besides GII.4 and GI.3) in Delhi. This is also the first report of NoV GI.5 from India. A change in prevalence pattern and increased diversity from 2009 to 2015 emphasizes the need for continued enteric virus surveillance to help measure the impact of new diarrhea vaccine(s) introduced in India.

  • 5. Harkonen, T
    et al.
    Paananen, A
    Lankinen, H
    Hovi, T
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Roivainen, M
    Enterovirus infection may induce humoral immune response reacting with islet cell autoantigens in humans2003In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 69, no 3, p. 426-440Article in journal (Refereed)
    Abstract [en]

    Molecular mimicry is one of the mechanisms by which enterovirus infections have been postulated to have a role in the pathogenesis of type 1 diabetes. Immunogenic epitopes in enterovirus capsid protein VP1 and procapsid protein VP0 have sequence similarities with diabetes-associated epitopes in tyrosine phosphatase IA-2/IAR and heat shock protein 60. In the present study, documented enterovirus infection was shown to induce humoral responses, that in 7% and 1% of patients cross-reacted with the known diabetes-associated epitopes in tyrosine phosphatase IAR and heat shock protein 60, respectively. In contrast, none of the children vaccinated against poliomyelitis had antibodies to the diabetes-associated epitope of tyrosine phosphatases IA-2/IAR. The antibody response studied in serum samples from six patients with coxsackievirus A9 infection was mainly targeted to capsid protein VP1. Coxsackievirus A9 infection induced antibodies cross-reacted with one epitope in heat shock protein 60, but not with epitopes derived from other autoantigens. Most diabetic children had high levels of antibodies to both coxsackievirus and poliovirus derived VP1 peptides but the pattern of reactivity did not differ from that seen in healthy children. The reactivity of linear epitopes derived from autoantigens was low in general and associated with the presence of multiple autoantibodies in the patients. Some linear auto-epitopes derived from tyrosine phosphatase IA-2, glutamic acid decarboxylase 65, preproinsulin, and heat shock protein 60 were recognized by sera from diabetic patients, but not by sera from healthy children. In conclusion, enteroviruses may induce immune responses that react with islet cell autoantigens, which is a concern when a putative inactivated enterovirus vaccine is considered.

  • 6.
    Istrate, Claudia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Hammarström, Lennart
    Division of Clinical Immunology, Karolinska University Hospital, Sweden.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Individuals with selective IgA deficiency resolve rotavirus disease and develop higher antibody titers ( IgG, IgG1) than IgA competent individuals2008In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 80, no 3, p. 531-535Article in journal (Refereed)
    Abstract [en]

    While IgA is proposed to be essential to control rotavirus disease, no information is available how IgA deficient individuals modulate rotavirus disease and immune responses. We report that individuals (n=62) with selective IgA deficiency ( IgA-D) (<0,05g/l) resolve rotavirus disease and show higher total IgG and IgG1 subclass antibody titers to rotavirus than IgA proficient individuals ( n=62) (GMT 18101 vs 4000 (p<0.005); 8463 vs 1691, (p<0.005). We conclude that IgA is not essential for resolving rotavirus infection in humans.

  • 7.
    Karlberg, Helen
    et al.
    Public Health Agency Sweden, Sweden; Karolinska Institute, Sweden.
    Sharifi-Mood, Batool
    Zahedan University of Medical Science, Iran.
    Mousavi-Jazi, Mehrdad
    Public Health Agency Sweden, Sweden.
    Dilcher, Meik
    University of Medical Centre Gottingen, Germany.
    Lindegren, Gunnel
    Public Health Agency Sweden, Sweden.
    Mardani, Masoud
    Shahid Beheshti University of Medical Science, Iran.
    Bereskly, Sandor
    Public Health Agency Sweden, Sweden.
    Weidmann, Manfred
    University of Stirling, Scotland.
    Mirazimi, Ali
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Public Health Agency Sweden, Sweden; Karolinska Institute, Sweden; National Vet Institute, Sweden.
    Molecular and Serological Findings in Suspected Patients With Crimean-Congo Hemorrhagic Fever Virus in Iran2015In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 87, no 4, p. 686-693Article in journal (Refereed)
    Abstract [en]

    Crimean-Congo hemorrhagic fever (CCHF) is an arthropod-borne disease of humans associated with a severe clinical picture, including hemorrhagic syndrome and a high mortality rate. CCHF virus is widely distributed throughout large areas of the world. To characterize the serological status in CCHF patients, paired clinical samples were collected from suspected CCHF patients and analyzed by microbiological and other laboratory analyses with the aim of: determining the presence of neutralizing antibodies against CCHF virus; investigating the cross-reactivity of these neutralizing antibodies against virus isolated from the same outbreak and against other available laboratory strain; and studying the relationship between the isolated virus with other virus by whole genome sequencing. Patients at Boo-Ali Hospital, Zahedan, Iran, with clinical symptoms ranging from mild to severe hemorrhagic fever were included in the study. Two serum samples were taken from each patient, the first as soon as the patient matched the criteria for CCHF notification and the second when the patient was discharged from hospital (2 weeks later). Commercial and in-house assays revealed a positive IgM signal in acute serum samples from six patients. A novel finding was that CCHF patients develop neutralizing antibodies soon after infection. Interestingly these antibodies were able to neutralize other CCHF virus strains too. The complete sequence of the Zahedan 2007 isolate, including the hitherto unknown first L-segment sequence, was identified using an original clinical sample from one patient with confirmed CCHF infection.

  • 8. Karttunen, A
    et al.
    Pöyry, T
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ilonen, J
    Hovi, T
    Roivainen, M
    Hyypiä, T
    Variation in enterovirus receptor genes.2003In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 70, p. 99-108Article in journal (Refereed)
  • 9.
    Oluwatoyin Japhet, Margaret
    et al.
    Obafemi Awolowo University, Nigeria .
    Adeyemi Adesina, Olufisayo
    Obafemi Awolowo University, Nigeria .
    Famurewa, Oladiran
    Ekiti State University, Nigeria .
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Molecular epidemiology of rotavirus and norovirus in Ile-Ife, Nigeria: High prevalence of G12P[8] rotavirus strains and detection of a rare norovirus genotype2012In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 84, no 9, p. 1489-1496Article in journal (Refereed)
    Abstract [en]

    Rotavirus (RV) and norovirus (NoV) are considered the most common causes of viral gastroenteritis in children. In this study, the prevalence of RV and NoV infection in 55 children with diarrhea from the rural community Akinlalu in Southwestern Nigeria was investigated using real-time PCR assays. The RV and NoV strains were genotyped by PCR and/or sequencing. RV and NoV infections occurred with a prevalence of 34.5% and 25.5% respectively, with predominance in children andlt;1 year. Most infections occurred during the dry season with increasing prevalence of RV as the dry season progressed (OctoberJanuary). Infections with RV VP6 subgroup (SG) II were more prevalent (27.3%) than SGI (7.3%). Similarly, NoV genogroup II infections were more common (23.6%) than genogroup I (1.8%). Five children out of 55 (9.1%) were co-infected with both RV and NoV. Notably, G12P[8] was the predominant RV strain (36.8%, n?=?7), observed for the first time in Nigeria. The VP7 gene of the G12 strains clustered within lineage III, sharing high nucleotide identity with each other (andgt;99%) indicating introduction in Nigeria from a single donor. Furthermore, a putative novel genotype within genogroup I NoV was detected, which till date has only been reported once in humans. To conclude, a high prevalence of the emerging G12P[8] RV strain was observed for the first time in Nigeria, as well as a putative novel NoV genotype in humans. These results provide new information which can be important for future vaccine evaluations and possible introduction in Nigeria.

  • 10.
    Paananen, A
    et al.
    Finland.
    Savolainen-Kopra, C
    Finland.
    Kaijalainen, S
    Finland.
    Vaarala, Outi
    National Public Health Institute, Helsinki.
    Hovi, T
    Finland.
    Roivainen, M
    Finland.
    Genetic and phenotypic diversity of echovirus 30 strains and pathogenesis of type 1 diabetes2007In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 79, no 7, p. 945-955Article in journal (Refereed)
    Abstract [en]

      Several enterovirus serotypes should be considered as potentially diabetogenic. The capacity of an enterovirus to kill or impair the functions of human -cells can vary among the strains within a given serotype as shown previously for echovirus 9 and 30 (E-30). The evolution of E-30 has also shown patterns correlating with the global increase of type 1 diabetes incidence. In the present study, antigenic properties of a set of E-30 isolates were investigated and the results correlated with the previously documented -cell destructive phenotype of the strains, or to genetic clustering of the strains. No simple correlation between the three properties was observed. A full-length infectious clone was constructed and sequenced from one of the isolates found to be most destructive to -cells (E-30/14916net87). Phylogenetic analyses demonstrated that this strain was closely related to the E-30 prototype strain at the capsid coding region while outside the capsid region prototype strains of several other human enterovirus B serotypes clustered more closely. This suggests that the relatively greater pathogenicity of the strain might be based on properties of the genome outside of the structural protein coding region. Neutralizing antibody assays on sera from 100 type 1 diabetic patients and 100 controls using three different E-30 strains did not reveal differences between the groups. This finding does not support a previous proposition of aberrant antibody responses to E-30 in diabetic patients. It is concluded that identification of the genetic counterparts of pathogenicity of E-30 strains requires further studies.

  • 11. Rodriguez-Diaz, Jesús
    et al.
    Banasaz, Mahanez
    Istrate, Claudia
    Buesa, Javier
    Lundgren, Ove
    Espinoza, Felix
    Sundqvist, Tommy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Rottenberg, Martin
    Svensson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology.
    Role of nitric oxide during rotavirus infection2006In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 78, no 7, p. 979-985Article in journal (Refereed)
    Abstract [en]

    The pathophysiological mechanisms behind rotavirus-induced diarrhoea still remain incomplete. Current views suggest that the non-structural protein 4 (NSP4) of rotavirus and the enteric nervous system (ENS) participate in water secretion and diarrhoea. In the present work the role of nitric oxide (NO) in rotavirus infection and disease has been studied in vitro, mice and humans. Incubation of human intestinal epithelial cells (HT-29) with purified NSP4 but not with infectious virus produced NO2/NO3 accumulation in the incubation media. The NSP4-induced release of NO metabolites occurred within the first minutes after the addition of the toxin. Mice infected with murine rotavirus (strain EDIM) accumulated NO2/NO3 in the urine at the onset for diarrhoea. Following rotavirus infection, inducible nitric oxide synthetase (iNOS) mRNA was upregulated in ileum, but not in duodenum or jejunum of newborn pups within 5 days post-infection. A prospective clinical study including 46 children with acute rotavirus infection and age-matched controls concluded that rotavirus infection stimulates NO production during the course of the disease (P < 0.001). These observations identify NO as an important mediator of host responses during rotavirus infection. © 2006 Wiley-Liss, Inc.

  • 12. Saijets, Salla
    et al.
    Ylipaasto, P
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Hovi, Tapani
    Roivainen, Merja
    Enterovirus infection and activation of human umbilical vein endothelial cells2003In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 70, no 3, p. 430-439Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal tract associated lymphoid tissue is considered to be the main replication site for enteroviruses. In order to invade tissues to reach pancreatic islets, cardiac muscles, and other secondary replication sites, the virus has to survive circulation in the blood and find a way to get through endothelial cells. In the present study, the susceptibility of human endothelial cells to infections caused by human parechovirus 1 and several prototype strains of enteroviruses, representing different species (human poliovirus, human enterovirus B and C), and acting through different receptor families was examined. Primary endothelial cells isolated from human umbilical vein by collagenase perfusion and also an established human endothelial cell line, HUVEC, were used. Primary endothelial cells were highly susceptible to several serotypes of enteroviruses (coxsackievirus A13, echoviruses 6, 7, 11, 30, and poliovirus 1). However, coxsackievirus A 9 and echovirus 1 infected only a few individual cells while human parechovirus 1 and coxsackie B viruses did not show evidence of replication in primary endothelial cells. In general, primary endothelial cells were more sensitive to infection-induced cytolytic effect than HUVEC. Activation of endothelial cells by interleukin-1▀ did not change the pattern of enterovirus infection. Immunofluorescence stainings of infected primary endothelial cells showed that expression of activation markers, E-selectin, and intercellular adhesion molecule-1, was clearly increased by several virus infections and the former molecule also by exposing cells to UV-light inactivated coxsackieviruses. In contrast, human leukocyte antigen-DR expression was not increased by virus infection.

  • 13.
    Simonen-Tikka, Marja-Leena
    et al.
    National Institute Health and Welf, Finland .
    Hiekka, Anna-Kaisa
    National Institute Health and Welf, Finland .
    Klemola, Paivi
    National Institute Health and Welf, Finland .
    Poussa, Tuija
    StatConsulting TuijaPoussa, Finland .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Korpela, Riitta
    University of Helsinki, Finland .
    Vaarala, Outi
    National Institute Health and Welf, Finland .
    Roivainen, Merja
    National Institute Health and Welf, Finland .
    Early human enterovirus infections in healthy Swedish children participating in the PRODIA pilot study2012In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 84, no 6, p. 923-930Article in journal (Refereed)
    Abstract [en]

    Human enteroviruses (HEV) are common, especially in childhood and during the enterovirus season, causing mainly asymptomatic infections but also mild and severe illnesses. Numerous studies have shown the association between HEV infections and type 1 diabetes. Here, the prevalence of HEV infections was studied in healthy Swedish children with increased HLA-associated risk for type 1 diabetes participating in the PRODIA pilot study in which children were randomized to receive probiotics or placebo during the first 6 months of life. Stool specimens collected from 197 children in every 3 months from the age of 3 to 24 months were screened for HEV using traditional viral culturing method and identified with reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing of the partial VP1 coding part of the viral genome. Altogether 4.8% (52/1,094) of the specimens were HEV-positive and 22.3% (44/197) of the children excreted HEV during the follow-up. HEV-A and HEV-B were present in 2.1 and 2.7% of the specimens, respectively. HEV-C and HEV-D viruses were not detected. In total, 17 different HEV serotypes were detected and the most common findings were CV-A9 (13.5%), CV-A16 (11.5%), and CV-A2 (9.6%). The majority of the infections (92.3%) were during the enterovirus season extending from July to December. Probiotic treatment did not affect significantly the risk of HEV infections during the 2-year follow-up although a trend for transient decrease for HEV positivity (HEV-A and/or HEV-B) by the age of 12 months was observed in children who received probiotics [OR 0.40; 95% confidence interval 0.15 to 1.08; P-value 0.071, generalized estimating (GEE) analysis]. According to the results, HEV-A findings were nearly as common as HEV-B findings among the healthy children participating in this study. Also it was shown that serotypes belonging to HEV-A species can be detected by means of viral culturing.

  • 14.
    Viskari, Hanna
    et al.
    JDRF Center for Prevention of Type 1 Diabetes, Finland and Department of Virology, University of Tampere, Tampere, Finland.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Uibo, Raivo
    Department of Immunology, University of Tartu, Tartu, Estonia.
    Salur, Lina
    Department of Immunology, University of Tartu, Tartu, Estonia.
    Marciulionyte, Dalia
    Institute of Endocrinology, Kaunas University of Medicine, Lithuania.
    Hermann, Robert
    Department of Pediatrics, University of Pécs, Pécs, Hungary.
    Soltesz, Gyula
    Department of Pediatrics, University of Pécs, Pécs, Hungary.
    Fuchtenbusch, Martin
    Diabetes Research Institute, Münich, Germany.
    Ziegler, Anette-G
    Diabetes Research Institute, Münich, Germany.
    Kondrashova, Anita
    JDRF Center for Prevention of Type 1 Diabetes, Finland, Department of Virology, University of Tampere, Tampere, Finland, Department of Pediatrics, University of Petrozavodsk, Russia.
    Romanov, Anatolij
    Department of Pediatrics, University of Petrozavodsk, Russia.
    Knip, Mikael
    JDRF Center for Prevention of Type 1 Diabetes, Finland, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland, Department of Pediatrics, Tampere University Hospital, Tampere, Finland .
    Hyoty, Heikki
    JDRF Center for Prevention of Type 1 Diabetes, Finland, Department of Virology, University of Tampere, Tampere, Finland, Department of Clinical Microbiology, Center for Laboratory Medicine, Tampere University Hospital, Tampere, Finland.
    Relationship between the Incidence of Type 1 Diabetes and Enterovirus Infections in Different European Populations: Results from the EPIVIR Project2004In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 72, no 4, p. 610-617Article in journal (Refereed)
    Abstract [en]

    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. © 2004 Wiley-Liss, Inc.

  • 15.
    Wang, Z
    et al.
    The Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
    Konya, J
    The Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
    Åvall Lundkvist, Elisabeth
    Department of Gynecologic Oncology, Karolinska Institute, Stockholm, Sweden.
    Sapp, M
    Department of Medical Microbiology, University of Mainz, Mainz, Germany.
    Dillner, J
    The Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
    Dillner, L
    The Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.Department of Laboratory Medicine, Section of Clinical Virology, Karolinska Institute, Stockholm, Sweden .
    Human papillomavirus antibody responses among patients with incident cervical carcinoma.1997In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 52, no 4Article in journal (Refereed)
    Abstract [en]

    The human papillomavirus (HPV) is recognized as a major cause of cervical cancer precursor lesions. HPV serology is a key method in the continuing elucidation of the importance of HPV exposure for cancer development and in predicting HPV-associated diseases. To extend previous HPV serological studies on cervical cancer, serum samples from a consecutive series of 216 women with incident untreated cervical carcinoma and 243 age- and sex-matched healthy blood donors were evaluated for the presence of antibodies against HPV capsids, a marker of past or present HPV exposure, as well as against several cervical cancer-associated defined HPV epitopes. Among the capsid antibody responses, HPV type 16 seropositivity had the strongest association with cervical cancer (OR 2.7, 95% CI 1.8-4.2), but HPV 18 and HPV 33 seropositivities were also significantly associated with cervical cancer (OR 1.6, 95% CI 1.1-2.5; and OR 1.5, 95% CI 1.0-2.2, respectively). The antibody responses against the defined HPV epitopes were confirmed to be associated with cervical cancer, at ORs ranging from 1.4 to 2.0. In conclusion, the study confirms that antibodies against defined HPV epitopes are associated with cervical cancer and provides evidence that seropositivities for HPV types 16, 18, and 33 are associated with cervical cancer risk.

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