Longitudinal study of parechovirus infection in infancy and risk of repeated positivity for multiple islet autoantibodies: the MIDIA study

The objective of this study was to investigate a possible association between human parechovirus infections in early infancy, diagnosed in fecal samples, and the development of islet autoimmunity. In the 'Environmental Triggers of Type 1 Diabetes: The MIDIA study', newborns with the highest genetic risk for type 1 diabetes were identified and followed with regular fecal sampling and questionnaires. A nested case-control study, including 27 children who developed islet autoimmunity (repeatedly positive for two or three autoantibodies) and 53 children matched for age and community of residence was used. Monthly stool samples from these children were analyzed for human parechovirus using a semi-quantitative real-time polymerase chain reaction. There was no significant difference in the prevalence of human parechovirus in stool samples when cases and controls were compared: 13.0 and 11.1%, respectively. There was also not any difference as to the number of infection episodes. In analyses restricted to samples collected 3, 6 or 12 months prior to seroconversion for islet autoantibodies, there was a suggestive association in the shortest time window of 3 months (20.8 vs. 8.8%, odds ratio = 3.2, 95% CI 1.2 - 8.5, uncorrected p = 0.022). No symptoms were associated with human parechovirus infection. A subset of the positive samples (n = 31) were sequenced, suggesting that human parechovirus 1 was the dominant genotype. The present study does not support strong associations between human parechovirus infections and the signs of islet autoimmunity. The weak association of parechovirus present in the last 3 months before development of autoimmunity warrants further investigation.