tetanus booster in adults: ??necessary??

 A really huge database assessment found no benefit of giving adults tetanus/diphtheria vaccine boosters if they completed their childhood vaccines (see tetanus booster adults CID2021 in dropbox, or DOI: 10.1093/cid/ciaa017 ). 

 

Details: 

-- observational cohort study using secondary sources from the World Health Organization (WHO) and World Bank, from 2001-17

-- main outcomes assessed: differences in reported tetanus and diphtheria clinical infections globally, stratified by whether adult booster vaccines were given or not as recommended by the individual country's vaccine schedule

Results: 

Tetanus

-- for 11.6 billion person-years of data from 31 North American and European countries, the tetanus incidence range per 1 million person-years: 

   -- for those countries recommending adult vaccination (Group 1):

        -- North America (3 countries): 0.09-0.42 

        -- Europe (19 countries): 0-1.08 

   -- for those not recommending adult vaccination  (Group 2):

        -- Europe (9 countries): 0-1.14 

 

 

  

-- this chart shows that overall there was no difference between tetanus incidence rates in those vaccinated as kids and adults (Group 1) and those only as kids (Group 2) 

 -- One poignant example is UK vs France: they are proximate in location/climate, are both large and with similar socioeconomic status, have similar childhood vaccination schedules (5 doses for tetanus/diphtheria), have similar infant vaccination coverage (95%). for adults, France recommended booster every 10 years and had 79% documented tetanus vaccine coverage until 2012, but then changed in 2014 to a 20-year vaccination schedule for those <60yo. But the UK never recommended boosters to those getting their primary series as kids: 

    -- from the above table: France had 0.21 cases/1,000,000 person-years whereas the UK  had 0.12 cases/1,000,000 person-years 

-- another graph compared Group 1 and Group 2 over time, showing a decline in tetanus cases overall, but a similar trend if vaccinated as adults or not: 

 

 

Diphtheria: pretty much the same story:

  -- comparing the UK and France, as done above with tetanus, with 1.8 billion person-years of combined diphtheria-tetanus vaccines: 

        -- France had a 57% vaccine coverage for 10-year boosters in those >16yo (similar to coverage in the US, at about 63%) 

        -- France: 0.06 cases/million 

        -- UK: 0.03 cases/million 

            --ie, really low numbers of cases, and no difference if they got the combined tetanus-diphtheria (Td) vaccine 

    -- and, comparing 13.4 billion- person-years from 31 countries:  

        -- in those recommending adult combined vaccine (tetanus and diphtheria): 0.05 cases/million person-years (and there were only 4 cases reported in the US from 2001-2016) 

        -- in those without adult boosters: 0.02 cases per million person-years (this was statistically significant, with fewer cases in those without adult vaccines, but Latvia was an extreme outlier in Group 1 with 10.06 cases per million; excluding, there wasno significant difference between Group 1 and 2) 

 

Commentary: 

-- in the US, the vaccination schedule for tetanus vaccines in adults has evolved over the years: in 1955 tetanus/diphtheria shots for adults were recommended every 3 years, then every 5 years in 1964, then every 10 years in 1966, where it now stands 

-- the WHO in 2021 reinforced that there was no need for adult tetanus immunization, noting “to ensure lifelong protection against tetanus in all people, [they] should receive 6 doses (3 primary plus 3 booster doses) of tetanus toxoid-containing vaccine (TTCV) through routine childhood immunization schedules”, per https://cdn.who.int/media/docs/default-source/immunization/immunization_schedules/immunization-routine-table1.pdf?sfvrsn=c7de0e97_9&download=true ; this recommendation is followed by at least 10 European countries. Similarly for the diphtheria component 

-- I do need to bring up an interesting personal anecdote. My oldest son had a pretty dramatic diffuse urticarial reaction to his second DTaP shot at 4 months old (a very uncommon event), so he never completed his childhood tetanus series. He had several antibody titers done over the years and was found to have high titers. Ultimately, at age 18, he had another titer, still high, but we decided to have allergy testing done (now negative, as is common) and a booster tetanus shot. So, seemed like pretty profound  and long-lasting immune response to just 2 vaccinations as an infant… 

-- overall, tetanus-related deaths have declined >99% and diphtheria-related deaths by >99.9%. it is notable in the above numbers that there is <1 case of tetanus per 3 million person-years, independent of the adult vaccination schedule 

-- in the US there are about 25 cases of tetanus a year, despite the fact that the causative microbe Clostridium tetani is ubiquitous in nature. The large majority of these cases are from those without the primary vaccination series. I cannot find new data on this, but my tracking of tetanus over the past few decades had confirmed that essentially all US cases (which were really uncommon) were in people coming to the US who had never had their primary vaccinations as kids

    -- it may well be that the persistent immunity against tetanus after the initial vaccinations as kids is related to the fact that the microbe is in fact all over the place, we are all pretty likely to have repeated exposures, and these exposures might regularly boost our immune response.  

-- this study assessed the incidence of actual infections, and not just the apparent robust antibody responses to immunizing kids only, and finding that those countries recommending adult vaccinations had no difference in tetanus or diphtheria incidence vs countries not recommending adult vaccinations in those having had a primary childhood series. And 95-97% of tetanus cases are in adults >20yo, so the difference in adults vaccinated vs not should have been evident in this study 

 

--in the US, the vaccination schedule for adults includes the use of the Tdap vaccine (tetanus-diphtheria-pertussis) on the 10-year cycle. In terms of the pertussis component, it seems that that protection is very short-lived after the adult booster, much less than even the 10-year frequency: 

    -- see http://gmodestmedblogs.blogspot.com/2018/10/pertussis-epidemics-increasing.html: a blog noting a significant increase in pertussis cases in the US from 2000-2016, likely attributable to the less immunogenic but better tolerated acellular pertussis vaccine (the only one available in the US).  

    -- see http://gmodestmedblogs.blogspot.com/2015/05/pertussis-vaccine-in-adolescents-and.html noting pretty significant decline in vaccine effectiveness for clinical pertussis beginning 12 months after the vaccination during the 2012 pertussis outbreak in Washington State, going from a peak of 73% in the first year, to 55% in the next year, and to 34% by the 2-4 year time period 

 

-- this WHO study only dealt with routine vaccinations and not tetanus infections after wounds or in pregnancy. These are separate issues. There are no data that I can find on clinical outcomes with or without Td or Tdap boosters in these scenarios, likely given the miniscule numbers of cases of tetanus that exist (ie, this would be a very difficult thing to measure to achieve statistical significance with so few cases). But: 

    -- for wounds, the recommendation is that if it is a puncture wound, then repeat tetanus booster at 5 years. Again, my guess is that lots of people have not had any boosters and puncture wounds are really common, so I would think that there might be an increased number of clinical tetanus cases in the above study if tetanus were reasonably common after "dirty" puncture wounds. But, I guess, the better part of valor still would be to just give a booster…. 

    -- for pregnant women, the recommendation is a Tdap booster at 27-36 weeks of pregnancy. This is to provide a robust passive transfer of pertussis-specific IgG immunoglobulins to the fetus, since the infants' vaccination series begins at 2 months of age. Again, no data on effectiveness and no bump in cases in those nonimmune. The epidemiologic data in the US from 2000-2016 found increases in pertussis overall in infants <1yo, which represented 15% of all cases with a rate of 75/100K infants (the highest of any age group), see http://gmodestmedblogs.blogspot.com/2018/10/pertussis-epidemics-increasing.html . No breakdown by age 0-2months (when the passive transfer of IgG would most likely be beneficial) and no breakdown by vaccination status. But, again, the better part of valor would be to immunize pregnant women during the 27-36 weeks of pregnancy to optimize the potential infant benefit (optimal timing is actually at around 30 weeks of gestation). also, see  ACOG recommendations https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/09/update-on-immunization-and-pregnancy-tetanus-diphtheria-and-pertussis-vaccination ; the Canadian recommendations are to immunize a pregnant woman between 27-32 weeks gestation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248450/ 

 

Limitations: 

-- only resource-rich countries were included in the analysis, and the baseline incidence of tetanus and diphtheria exposures may be different in other countries, with different living situations, climates, sanitation, public health systems, health care systems, etc. All of these might influence the prevalence and exposures to these pathogens and others.  

-- these are all observational data. no patient-specific information on the actual individual vaccines received as a child or an adult. some of the adults in the study may have had boosters because of the way-too-common puncture wounds, or pregnancy, or patient/provider preference, which all might affect the results

so,

-- lots of information on lots of people in many different countries finding that the incidence of tetanus and diphtheria cases, both extremely uncommon, do not seem to be averted with adult booster vaccination

-- there may be some benefit of the pertussis component, but that seems to be quite transient. and the 10-year vaccination schedule probably does not do much. if there is a real concern about pertussis outbreaks, these vaccines would likely require patients to get boosters right at the beginning of the outbreak. or:

    -- develop a more immunogenic vaccine, like the old pertussis component we used to give (but without the high fevers, etc from them)

    -- give the vaccine (perhaps just the pertussis component) more frequently if using the current acellular vaccine

-- but, the above data are pretty clear that at least in the countries assessed (high-income ones in the Western Hemisphere), there is no significant benefit regarding tetanus and diphtheria from adult vaccination if the patient has had the full childhood series

-- i am not, believe it or not, an anti-vaxer... i have had my 5 Covid shots. And, childhood immunizations have had profound benefits (it is now rare to have a kid to have severe HIB or pneumococcal infections, or varicella, or polio or smallpox, or .....). but we should make sure that the suggested vaccines and vaccination schedules do have clinical benefits. Of course, in the beginning, we do need to assess harm/benefit the best we can and make reasonable guesses often based on our understanding of the physiology and animal studies (the bivalent covid vaccine, for example, has little data to support it, but it still makes sense, especially in the older patients: see http://gmodestmedblogs.blogspot.com/2022/09/covid-does-it-make-sense-to-give-young.html ). But the imperative is to continue assessing vaccine risks/benefits over time, as this study did, so that vaccination schedules can be modified to make sure that real clinical benefit outweighs the real risks...

geoff

 

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