Update: Pediatric diabetes

Abstract

The germ theory of disease was first described after the 16th century and further propagated by pioneers such as Lister, Koch, Pasteur, and Metchnikoff. Many such theories of viral causality of type 1 diabetes (T1D) have been explored, but no definitive results have been available. Adding to this body of work are researchers at Murdoch Children s Research Institute in Melbourne, Australia, who wrote a letter to the editors at JAMA Pediatrics in January 2019 titled Association of Rotavirus Vaccination With the Incidence of Type 1 Diabetes in Children. That study explored the incidence of T1D in Australian children 7 to 8 years before and after the introduction of the rotavirus vaccine. In the study, during the period of evaluation between 2000 and 2015, 16,159 new cases of T1D in children aged between 0 and 14 years were detected. The authors noticed a 14% reduction in the incidence of T1D in children between 0 and 4 years of age after the introduction of the rotavirus vaccine in 2007. No such change in incidence was noted in older children between the two time periods. The authors believed this to be the first report of a lower incidence of T1D in children following introduction of the rotavirus vaccine, and they intend to follow this with a case-control linkage study to further explore the association. A recent review titled Rationale for Enteroviral Vaccination and Antiviral Therapies in Human Type 1 Diabetes published in Diabetologia in December 2018 also discusses this infectious theory of T1D. In the review, Dunne et al. discuss the various factors that have gone against this theory, including the high incidence of enteroviral infections in the general population compared with T1D, prolonged incubation periods with asymptomatic infections, and the inability to always isolate a high viral load of a pathogen from the pancreas. However, they introduce the concept of a multiple-hit hypothesis based on the isolation of multiple enteroviruses and different strains of viruses in donor pancreas and peripheral blood mononuclear cells from biobanks. Dunne et al. hypothesize that multiple infections may lead to the development of autoimmunity in T1D by molecular mimicry, cross-reactivity, and inflammation causing β-cell dysfunction. The paper also proposes a vaccine against enteroviruses to be adapted during routine immunization in infancy as primary prevention. The authors inform us of a 2018 randomized control trial using placebo and two antiviral medications in individuals with newly diagnosed T1D to preserve β-cell function. The paper on rotavirus vaccines and T1D discusses an association between the two and does not indicate causality. Several such studies have been performed in the past without replicability. The second paper makes valid arguments supporting enteroviral infections, but the counterarguments that the authors make first need to be debunked. It is perhaps too early to discuss universal prevention of T1D, but it would certainly be prudent to study the utility of vaccines and antiviral therapy to prevent β-cell destruction.