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Sioofy-Khojine, A.* ; Oikarinen, S.* ; Honkanen, H.* ; Huhtala, H.* ; Lehtonen, J.P.* ; Briese, T.* ; Hyoty, H.* ; TEDDY Study Group (Ziegler, A.-G. ; Beyerlein, A. ; Hummel, M. ; Hummel, S. ; Knopff, A. ; Scholz, M. ; Stock, J. ; Warncke, K. ; Wendel, L. ; Winkler, C.)

Molecular epidemiology of enteroviruses in young children at increased risk of type 1 diabetes.

PLoS ONE 13:e0201959 (2018)

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BackgroundYoung children are susceptible to enterovirus (EV) infections, which cause significant morbidity in this age group. However, the current knowledge regarding the epidemiology of EVs and the circulating virus strains is mostly based on viruses detected in children with severe diseases leading to contact with the health care system, while the vast reservoir of EVs that circulate in the general population is less characterized.MethodologyThe present study investigates the types and the prevalence of EVs circulating in the young children of the background population in Georgia, Colorado, and Washington State in the USA, and Germany, Sweden, and Finland in Europe.A total of 4018 stool samples, collected monthly from 300 healthy and non-hospitalized children at the age of 3 +/- 18 months in 2005 +/- 2009, were analyzed for the presence of EVs using RT-PCR, followed by sequencing of the VP1-2A region of the viral genome to type the EV(s) present. All of the children carried type HLA-DQ2 or -DQ8 alleles associated with type 1 diabetes.Principal findingsAltogether 201 children (67%) were found to be EV positive. The prevalence was much lower in Finnish children (26%) than in the children of the other counties combined (75%). Infections increased by age and showed a nadir during the winter months. Children who carried both the HLA-DQ2 and -DQ8 alleles had less infections than children who were homozygous for these alleles. Coxsackieviruses type A were the most frequently detected viruses in all geographical regions. Coxsackievirus type A4, Echovirus type 18, and Echovirus type 25 were shed for longer time periods than the other EV types.ConclusionsCompared to prevalence data from symptomatic patients requiring medical attention, this study provides a better view of EVs circulating in young children in the USA and in Europe. The observations may prove useful for the selection of strategies for designing EV vaccines in the future. The study also confirms our previous serological findings suggesting that EV infections are relatively rare in Finland.

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