Investigators found the first evidence of a decline in type 1 diabetes incidence following implementation of the oral rotavirus vaccine into a routine immunization schedule.
Kirsten Perrett, PhD
Rotavirus, which directly infects pancreas cells and causes cell death via apoptosis, has previously been associated with type 1 diabetes (T1D).
To further investigate whether natural infection with the virus was a causative factor in T1D, a team of investigators analyzed publicly available data in Australian children following the introduction of the rotavirus to the Australian National Immunisation Program in 2007 regarding the incidence of T1D in Australian children before and after the oral RV vaccine.
Among their findings, the team found the first evidence of a decline in T1D incidence following implementation of the oral rotavirus vaccine into a routine immunization schedule.
“This was a theoretical basis for the idea that an immune response to rotavirus could end up cross-targeting and killing the beta cells,” Kirsten Perrett, PhD, told MD Magazine®. “Because of this ‘molecular mimicry,’ we first wanted to rule out the possibility that rotavirus vaccination might in itself promote type 1 diabetes.”
Perrett and her team decided to take a closer look at an interrupted time-series analysis regarding the incidence of newly diagnosed T1D in Australian children in the 8 years before the May 2007 introduction of routine oral RV vaccination compared with the 8 years after for all infants aged 6 weeks and older. At that time, the national coverage for rotavirus vaccine was 84%.
By using publicly available data from the National Diabetes Services Scheme via the Australian Institute of Health and Welfare, the team determined the observed and modeled rates of new-onset T1D between 2000 and 2015. The team also sourced the Australian Bureau of Statistics for population numbers for children aged 0 to 4 years, 5 to 9 years, and 10 to 14 years in Australia over this period.
Stata version 14.2 (StataCorp) was used to perform the analysis from August 2017 to September 2018, and significance was classified as 2-sided P values less than .05.
Approximately 16,159 cases of newly diagnosed T1D cases were documented between 2000 and 2015 in 66,055,000 person-years among children aged 0 to 14 years, equating to a mean rate of 12.7 (95% CI, 11.0-14.8) cases per 100,000 children.
After the introduction of oral RV vaccine in 2007, the number of incident cases of T1D decreased by 14% (rate ratio, .86 [95% CI, 0.74-.99]; P = .04) in children aged 0 to 4 years. However, in the preintervention and postintervention patterns, there was no evidence of a change over time. During the entire 16-year period, there was no change in the number of incident cases or temporal differences in children aged 5 to 9 years and 10 to 14 years.
While the incidence of T1D has consistently increased over the past decades, the Perrett and her team noted that the rise may be slowing or even plateauing.
“The study findings that the incidence of type 1 diabetes decreased in 0- 4-year-olds following the introduction of the vaccine is exciting and consistent with the hypothesis that oral RV vaccine may be protective against the development of type 1 diabetes in early childhood,” Perrett said. “However, this finding is only preliminary.”
In a Finnish population-based cohort study that included a relatively small number of cases and a shorter timeframe, investigators drew an inconclusive association between oral RV vaccination and type 1 diabetes or celiac disease risk. Investigators noted that owing to genetic and environmental differences at the population level, response to RV vaccination could vary by geographical location.
Perrett added that ecological associations are the weakest form of evidence, which is why she and her team plan to explore the association in an individual-level case-control linkage study, which will or will not provide the strongest epidemiological evidence for an association between rotavirus vaccination and a decrease in the incidence of type 1 diabetes in Australia. Results of this linkage study will be available towards the end of 2019.
“A separate study will follow up on reports by other investigators that the pancreas in children who develop type 1 diabetes is smaller than normal,” Perrett said. “This is consistent with what we found and reported after rotavirus infection in the mouse. We are therefore undertaking a longitudinal study of genetically at-risk children from pregnancy (endia.org.au) in which infections and pancreas size are being monitored.”
The study, titled, “Association of Rotavirus Vaccination With the Incidence of Type 1 Diabetes in Children,” was published online in the Journal of American Medical Association (JAMA) Pediatrics.