Wednesday, April 17, 2019

Can A Rotavirus Vaccine Prevent Type 1 Diabetes In Some People?

In this blog posting I'm discussion an observational study, that is, a study where different groups of people are observed to see if their differences cause more or less disease.  This is quite different than the intervention studies that I usually cover.  Intervention studies are much better controlled and their results are more likely to be supported by future research.   However, I though this study was interesting enough to discuss even as an observational study.

This is the Reuters headline:
Rotavirus vaccination tied to lower rates of type 1 diabetes

For comparison, this is the headline from The Scientist:
"Results from an observational study find that the introduction of a routine vaccine in Australia coincided with a fall in the incidence of the autoimmune condition."

So what data did they look at, and what did they see?

They looked at people diagnosed with type-1 diabetes in Australia, and compared the 8 years before 2007 to the 8 years afterwards.  That was the year the Rotavirus vaccine was universally introduced to Australia.  This analysis covered about 16,000 children who were diagnosed with T1D.  What they saw was that the number had been stable up until 2007, at 8.7 per 100,000 kids [d1].  However, after they started giving the vaccine to all babies, the rate dropped to 7.8 per 100,000, a drop of 14%.
Graph is from the published paper, and is presented
 for educational purposes only.


Discussion

Rotavirus or 2007?
For me the big, obvious question is: did the type-1 diabetes rate drop because of the Rotavirus vaccine or because of something else that happened in 2007?  In a sense, this is the only question that really matters.  If you only look at this study, there is no way to tell.  However, this research group has been studying the connection between Rotavirus and T1D for many years, and they do think the two are related, and it's not just some random 2007 thing.

I did a very quick literature search, and found several studies (including some done previously by this group), which showed a connection between rotavirus infection and type-1 diabetes.  There were also some computer simulation studies, and some "mechanistic" studies (showing how a Rotavirus infection might cause or speed up the development of type-1 diabetes).  So the idea that the two are linked is not far-fetched.

Just One Study? / What about other research?
Another question is: Are there other studies showing that a Rotavirus vaccine might lower type-1 rates?  Or, is this the only one? 

In my literature search,  I only found one similar study done in people.  The researchers compared type-1 diabetes rates in children who had been vaccinated against Rotavirus to children who had not (all born in the same year).  Rotavirus vaccination did not lower type-1 rates in this study [d3], and that is not promising.

I very much hope that these researchers perform similar analysis in other countries which introduced universal Rotavirus vaccination.  If they see that county X introduced the vaccine in 2010, and saw a drop in type-1 in 2010, that does two things at once: it confirms this study, and it suggests that the vaccine is important, rather than the year.

Does Prevention Matter? / Does 14% Matter?
I know many people touched by type-1 diabetes don't care about prevention.  And I understand that; after all, in a sense prevention is too late for them.  But I will continue to care about prevention, even though it will not help my daughter.  First, because I think we might learn something from a prevention that might lead to a cure in the future.  That is not always true, of course, but it certainly is possible.  Second, because someday my daughter may have kids of her own, and a prevention for my grandchildren would be worth a lot to me.  Third, just in general, I want the world to be a better place even if my family doesn't personally benefit.  And prevention will surely help many people in the future.  (Of course, there is a counter argument: that prevention will cause research money aimed at a cure to "dry up", because there will be less and less need of it in the future.)

Finally, some people will belittle the 14% drop.  They will point out, that's not a lot, and many people will still get type-1.  That is true, but for me, it's besides the point.  Right now, we have nothing that lowers the chance of type-1 diabetes after a person is born [d2].  So going from nothing to one thing, and going from 0% to 14% are both big improvements.  I don't think we should let the perfect become the enemy of the good when it comes to solutions.  A drop of 14% (if confirmed by future research) is an important first step.

More Reading
Details

[d1] I assume those numbers are just for people diagnosed between 0 and 4 years old.  They are much too small to be everyone diagnosed with type-1 diabetes.  Total type-1 rates in the US are generally between 1 in 250 and 1 in 500.

[d2] Universal Rubella (German Measles) vaccination is thought to lower the rate of type-1 diagnosis in the population (but no where near 14%).  However, it is generally believed that this is caused by preventing measles in pregnant women since contracting Rubella during pregnancy significantly raises the chance that the child will (eventually) be diagnosed with type-1.  So this is a pre-birth intervention.
https://www.diapedia.org/type-1-diabetes-mellitus/2104282116/the-congenital-rubella-syndrome-and-diabetes

[d3] The exact quote was: "The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69-1.20) for T1D ... in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk ... T1D during 4-6 years follow-up after vaccination."
This study covered 500 children.
https://www.ncbi.nlm.nih.gov/pubmed/28399059

Joshua Levy
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

1 comment:

Oscar said...

It is interesting to speculate on what causes the rise and fall of new cases of type 1 diabetes over time. I once found a number of panicked reports of new cases of diabetes in young people in contrast to old and overweight people emerging in English medical books of the early nineteenth century. This made me suspect that the rise may have had something to do with Britain being the first country to become industrialized, especially since I could only find similar concerns about new cases in young people in German works in the 1840s, which matches Germany's relatively delayed industrialization compared to Britain. There was also a sudden rise in new type 1 cases in Poland in the 1970s, which some attributed to increased industrialization there as well.

I think that type 1 diabetes is a 'gunpowder and match' disease, with the 'gunpowder' being an inherited predisposition of the immune system to respond excessively to some random threat, the 'match,' whether it is measles, chicken pox, or allergies, with the result that the overstimulated immune response goes on to attack the pancreatic beta cells. Thus any vaccination program will help a bit, but no program will ever be perfectly protective. The hygiene hypothesis may play a role here as well, with industrialization displacing the population away from germ-ridden farms and toward cleaner urban environments, where the immune system of children cannot learn to cope with a variety of challenges, and so lacks the strength and self-direction required to keep from producing auto-antibodies, hay fever, peanut allergies, and type 1 diabetes.