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Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life

Vaarala, Outi MD, PhD*; Jokinen, Jukka PhD; Lahdenkari, Mika Stud Soc Sc; Leino, Tuija MD, PhD

Author Information
The Pediatric Infectious Disease Journal: July 2017 - Volume 36 - Issue 7 - p 674-675
doi: 10.1097/INF.0000000000001600
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Abstract

Rotavirus infection has been suggested as a trigger of type 1 diabetes (T1D)-related autoimmunity1 and celiac disease (CD)-related autoimmunity.2,3 The possible mechanisms of rotavirus infection to trigger CD or T1D could be related to changes in the gut permeability and inflammation leading to the activation of the underlying autoimmunity, or rotavirus antigens could trigger autoimmunity via molecular mimicry.3–5

In Finland, the incidence of T1D in children is the highest in the world.6,7 In addition, unique personal identifier allows disease and immunization registers to be linked on the national level. The accuracy of the disease diagnoses and the registration coverage have been proven to be good in the secondary healthcare register (National Care Register)8 as more than 95% of discharges could be identified from the register and roughly 90% of diagnoses have been correctly stated when compared with medical records or additional data source.8 Oral attenuated rotavirus vaccination, RotaTeq (Merck), taken at 2, 3 and 5 months of age, was introduced into the Finnish National Immunization Program (NIP) in September 2009.

We designed a population-based cohort study to evaluate whether prevention of rotavirus infection with vaccination would affect the risk of CD and T1D diagnosed during 2009–2014 in Finnish children by comparing vaccinated and unvaccinated children in a cohort born in 2009–2010. Nationwide rotavirus vaccination records were extracted from the National Vaccination Register (NVR) during 2009–2011 and validated directly from local healthcare stations for a random sample of 495 children born from July 2009 to December 2009. Incident diagnoses of CD and T1D during 2009–2014 in the cohort were identified in the National Care Register, which includes all diagnoses made in Finnish hospitals. The child was considered vaccinated from the time of the first rotavirus vaccine dose, and incident cases in biannual cohorts were tabulated according to vaccination status at the time of diagnosis. Rates of CD and T1D in exposed and unexposed states were compared using Poisson regression, adjusted with baseline rate in biannual cohorts.

The commercial use of rotavirus vaccination prior NIP was approximately one third, and more than 90% within the frame of NIP introduction (Table 1). Validation study suggested that the NVR data were reasonably complete for this investigation (88.5% coverage based on NVR and 91.9% after validation).

T1
TABLE 1.:
The Diagnosis of Celiac Disease and Type 1 Diabetes During 2009–2014 in Finnish Birth Cohort of 2009–2010 Grouped According to the Rotavirus Vaccination Status

There were altogether 94,437 rotavirus vaccinated and 27,213 unvaccinated children in our study. We found 293 CD patients of whom 201 were vaccinated and 345 T1D patients of whom 243 were vaccinated. The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69–1.20) for T1D and 0.87 (0.65–1.17) for CD in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk of CD or T1D during 4–6 years follow-up after vaccination. A longer follow-up time is needed as time from the induction of autoimmunity to diagnosis may be several years, and incidence of CD and T1D is low among the age group below 5. Our results suggest that oral rotavirus vaccination is considered safe in the individuals at risk of CD and T1D.

REFERENCES

1. Honeyman MC, Coulson BS, Stone NL, et al. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes. 2000;49:13191324.
2. Stene LC, Honeyman MC, Hoffenberg EJ, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101:23332340.
3. Dolcino M, Zanoni G, Bason C, et al. A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84. Immunol Res. 2013;56:465476.
4. Honeyman MC, Stone NL, Harrison LC. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. Mol Med. 1998;4:231239.
5. Pane JA, Dang VT, Holloway G, et al. VP7 of Rhesus monkey rotavirus RRV contributes to diabetes acceleration in association with an elevated anti-rotavirus antibody response. Virology. 2014;468–470:504509.
6. Tuomilehto J, Virtala E, Karvonen M, et al. Increase in incidence of insulin-dependent diabetes mellitus among children in Finland. Int J Epidemiol. 1995;24:984992.
7. Karvonen M, Viik-Kajander M, Moltchanova E, et al. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care. 2000;23:15161526.
8. Sund R. Quality of the Finnish hospital discharge register: a systematic review. Scand J Public Health. 2012;40:505515.
Keywords:

Rotavirus vaccination; celiac diasease; type 1 diabetes

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