Higher parental occupational social contact is associated with a reduced risk of incident pediatric type 1 diabetes: Mediation through molecular enteroviral indices

Abstract

We aimed to examine the association between parental occupational social contact and hygiene factors on type 1 diabetes (T1D) risk and possible mediation of these effects through child enteroviral infection. We interviewed 333 incident T1D cases and 660 controls from 2008–2011 in Melbourne, Australia. Enteroviral indices (ribonucleic acid by reverse transcription polymerase chain reaction and Coxsackie B virus antibody levels) in peripheral blood were measured in nested case control samples. Parent occupational social contact was assessed by the number of well or sick children, adults or animals contacted daily through work. Higher parental occupational social contact was strongly associated with reduced T1D risk with evidence of dose response (contact with the well or sick score, Adjusted odds ratio (AOR) per category: 0.73 (95% Confidence Interval (CI): 0.66, 0.81); P<0.001 or AOR 0.63 (95% CI: 0.53, 0.75); P<0.001) respectively). Nine of the ten parental social contact indices, were significant mediated through one or more enteroviral indices. The strength of association between enterovirus presence and T1D onset increased with child age (1.2 fold increase per year; P = 0.05). Lower child hand hygiene enhanced the adverse effect of low parental occupational contact with the sick; Synergy Index 5.16 (95% CI: 3.61, 7.36). The interaction between hand washing and parental occupational contact is more consistent with protection against parental enteroviral shedding than the sharing of a protective infectious agent or microbiome.

Developing a vaccine for type 1 diabetes by targeting coxsackievirus B

“…The relationship between islet autoantibodies and CVB serotypes has also been observed in other cohorts collected in European countries [78] and subsequently in prospective studies carried out in Europe, North America, and Australia [79,80]. Recently, the large international TEDDY birth cohort study reported an association between detection of species B EVs (particularly CVBs) in stool samples by Illumina mass sequencing and subsequent initiation of islet autoimmunity (data presented in the Immunology of Diabetes Society meeting in London, October 2018).…”

Household size, T regulatory cell development, and early allergic disease: a birth cohort study

“…Maternal occupational social contact: levels Low, Medium, and High as outlined in 21 . Paternal occupational social contact: levels Low, Medium, and High as outlined in 21 . Disinfectant use in T1/2/3: values = none, <1 week, about 1 week, a few times per week, every day.…”

“…Any formal childcare in first 12 months: baby received any regularly scheduled formal childcare in a childcare center in the first 12 months, no otherwise. Maternal/Paternal occupational social contact: low or not elsewhere classified, medium 21 …”

“…Remoteness of location: lives in regional area or regional city, as the reference group. Maternal occupational social contact: levels Low, Medium, and High as outlined in 21 . Paternal occupational social contact: levels Low, Medium, and High as outlined in 21 .…”

“…Regarding aTreg postnatal development, parental occupational social contact was associated with higher aTreg at 12 months of age. This is a previously identified possible determinant of reduced type 1 diabetes 21 and higher child leukemia risk, 41 possibly through increased early infection, 21,41 reflecting that activated Treg cells develop in response to postnatal antigenic stimuli 42 …”