Using spatio-temporal surveillance data to test the infectious environment of children before type 1 diabetes diagnosis

PLoS One. 2017 Feb 2;12(2):e0170658. doi: 10.1371/journal.pone.0170658. eCollection 2017.

Abstract

The "hygiene hypothesis" postulates that reduced exposure to infections favours the development of autoimmunity and childhood type 1 diabetes (T1D). But on the other side, viruses, notably enteroviruses, are suspected to trigger T1D. The assessment of the possible relationships between infections and T1D still defies the classical tools of epidemiology. We report the methods and results of a geographical approach that maps the addresses of patients to a communicable diseases surveillance database. We mapped the addresses of patients at birth, infancy and T1D diagnosis to the weekly estimates of the regional incidences of 5 frequent communicable diseases routinely collected since 1984 by the French Sentinel network. The pre-diagnostic infectious environment of 3548 patients with T1D diagnosed between 0.5 and 15 years was compared to those of 100 series of age-matched "virtual controls" drawn randomly on the map. Associations were classified as "suggestive" (summer diarrhea, SD, and varicella, V) when p< 0.05, or "significant" (influenza-like infections, ILI) when they passed the Bonferroni correction for FDR. Exposure to ILI and SD were associated with T1D risk, while V seemed protective. In the subset of 2521 patients for which we had genome wide data, we used a case-only approach to search for interactions between SNPs and the infectious environment as defined by the Sentinel database. Two SNPs, rs116624278 and rs77232854, showed significant interaction with exposure to V between 1 and 3 years of life. The infectious associations found should be taken as possible markers of patients' environment, not as direct causative factors of T1D. They require replication in other populations. The increasing public availability of geographical environmental databases will expand the present approach to map thousands of environmental factors to the lifeline of patients affected by various diseases.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Autoimmunity / physiology
  • Child
  • Child, Preschool
  • Communicable Diseases / microbiology*
  • Communicable Diseases / virology*
  • Databases, Factual
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / physiopathology
  • Environment
  • Environmental Exposure*
  • Female
  • France
  • Genotype
  • Geography
  • Humans
  • Infant
  • Insulin-Secreting Cells / pathology
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Virus Diseases / pathology*

Grant support

This study was sponsored by ongoing institutional grants from NovoNordisk France and Lilly France, a specific Inserm support lasting from 2008 to 2014, the Programme Hospitalier de Recherche Clinique (PHRC ISIS-DIAB and ISIS-VIRUS), the Agence Nationale de la Recherche (ANR ENVIROGENEPIG), the Association pour la Recherche sur le Diabète (ARD). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. They also did not have access to the clinical trial database, nor any opportunity to review the manuscript. The corresponding author had full access to all the data in the study and final responsibility for the decision to submit for publication.