Are vaccinated people more or less healthy than unvaccinated people in the long term?

Question

Do peer-reviewed studies exist comparing the long-term health outcomes, broadly defined, between children who receive the current, full recommended vaccine schedule vs. completely un-vaccinated children?

By long term, I mean over 10+ years ideally, but at least over 5 years.

I understand there can be sensitivity about denying vaccination to children in order study such outcomes, but given that there are many families who are not in favor of vaccination for religious or other reasons, it seems there would be a sufficient pool of willing participants, and this is important question to have clear answers for.

Searches on this site and the internet produce some relevant results, but nothing that covers a broad range of health outcomes over a long time period. Also, many of these studies do find that there are adverse effects that should be studied further.

Therefore, there do not seem to be studies that could be considered conclusive on this question. Relevant references include:

• This is a CDC whitepaper scoping how the safety of the childhood vaccine schedule could be studied using the Vaccine Safety Datalink, but I could not find evidence that such studies were eventually performed. This whitepaper says, a 2012 Institute of Medicine "committee concluded that, while available evidence indicated that the current U.S. immunization schedule was safe, few published investigations had specifically examined the safety of the recommended childhood schedule as a whole."
• This study from 2020 shows evidence of "developmental delays, asthma, ear infections and gastrointestinal disorders" associated with childhood vaccination, but more research is called for. This critique describes problems with this study and provides additional citations regarding vaccine safety.
• This research summary from 1998 suggests more long term studies are needed, but I could find no citations of this summary suggesting such studies have been done.
• This study shows vaccine effectiveness, but also notes "Despite a low absolute risk of serious VAAEs [vaccine-associated adverse events], the relative risk of some VAAEs can exceed risk of disease."
• This is a study of adult military, not children.
• This study finds increases in educational and cognitive skills associated with vaccination.
• This study concludes "Linear regression analysis of unweighted mean IMRs showed a high statistically significant correlation between increasing number of vaccine doses and increasing infant mortality rates, with r = 0.992 (p = 0.0009). Using the Tukey-Kramer test, statistically significant differences in mean IMRs were found between nations giving 12–14 vaccine doses and those giving 21–23, and 24–26 doses. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRs is essential."

Answer 1

This is a far far trickier question than it would appear. The questions spring to mind - Which vaccines? What dose regimen (different countries have different schedules and included/excluded vaccines)? What outcomes would you define as "healthier"? Which populations are you looking at (those that get the illness or not?, compared to what?) and for how long (decades, life-long)?

I mean, in one sense, there's some pretty strong evidence that some vaccines, such as the Smallpox vaccine¹, protect from death or getting the illness, so by definition, this vaccine resulted in better health in both the short and long terms (i.e. they didn't die and any infection they did get was weaker and shorter lived...) for those vaccinated versus those unvaccinated. If you did get Smallpox (infection with Variola virus), you had a 30% chance of dying if unvaccinated and almost certain life-long scarring from the pox, as well as other potential injuries such as blindness from pustules on the eye. Indeed this vaccine was so effective at preventing the viral infection that we were able to eradicate the disease world-wide; a great victory for medical science.

Another similar one might be the Polio vaccine. Poliomyelitis, which is also caused by a virus, is asymptomatic in about 70% of cases, but in the other 30% can result in a rising paralysis (0.1-0.5%) and withering of the lower limbs (see picture in linked Wikipedia page), even causing death from paralysis of the nerves controlling the heart and breathing. Vaccination eliminates these complications almost entirely and prevents the disease almost entirely. This vaccine is so effective that we are closing in on elimination of this disease too. Thus this vaccine results in better long-term health outcomes for vaccinated vs. unvaccinated.

However, I suspect that you're not after this version of events - you could be looking for the short-term relatively mild illnesses that don't cause severe obvious defects. In this category I suspect you might include measles, mumps, rubella (vaccinated against with the MMR vaccine), and perhaps things like chickenpox (varicella virus) and maybe diphtheria (Corynebacterium diphtheriae)?

Well, Rubella causes deafness in approximately 60% of congenital rubella infections and also blindness in many ² - vaccination of the mother almost entirely eliminates congenital rubella. Diphtheria resulted in a small proportion of people dying from a thick plaque of dead tissue that developed over the throat, but also had issues like carditis and renal problems, which tend to be life-long problems once you have them. Vaccination against diphtheria results in almost no break-through infections. I would argue that these are better health outcomes. Similar results can be found for almost all illnesses that we have vaccines for.

You might not even be after those results; you could be after the population that gets the disease whether vaccinated or not (e.g. COVID-19 vaccines). I don't have time to find much in the way of referenced articles right now, but in almost all cases, severe illness is eliminated and good health maintained for those vaccinated, but the unvaccinated have poorer outcomes and more long-term effects (for COVID-19 myocarditis in the infected, unvaccinated population is about 0.01%, with vaccine this drops to about a 7th of that ³). Myocarditis is a life-long illness, so by this measure, even though we don't have decades or even 5 years of time, we can know that vaccination helps prevent this... a better health outcome.

The problem here is that many people think "Oh, the vaccine only prevents the illness", not about the complications to health that having the illness results in. All of the illnesses we vaccinate against (in the health systems that I am familiar with and that the WHO recommend) can result in serious health outcomes, some of which might not be visible for years after contracting the disease. A prime example of this is Human Papilloma Virus (genital warts) causing cervical cancers and oropharyngeal cancers (I'll leave it to you to figure out why it might cause cancers of the mouth and throat...) in people who have been infected with particular types of the virus, but these cancers might not show up for many decades after the infection.

Overall, vaccines prevent serious and not-so serious illnesses from naturally acquired infection, many of which have life-long sequelae.

References:

1. Belongia EA, Naleway AL. Smallpox vaccine: the good, the bad, and the ugly. Clin Med Res. 2003 Apr;1(2):87-92. doi: 10.3121/cmr.1.2.87. PMID: 15931293; PMCID: PMC1069029.

2. Tatiana Lanzieri, MD; Susan Redd; Emily Abernathy, MS; Joseph Icenogle. 2020. Chapter 15: Congenital Rubella Syndrome in Manual for the Surveillance of Vaccine-Preventable Diseases. CDC, USA.

3. Voleti N, Reddy SP, Ssentongo P. Myocarditis in SARS-CoV-2 infection vs. COVID-19 vaccination: A systematic review and meta-analysis. Front Cardiovasc Med. 2022 Aug 29;9:951314. doi: 10.3389/fcvm.2022.951314. PMID: 36105535; PMCID: PMC9467278.