Mumps immunity waning/more clinical outbreaks

​The NY Times had a recent article on mumps outbreaks after waning mumps immunity post-vaccination https://www.nytimes.com/2018/03/21/well/live/mumps-is-on-the-rise-a-waning-vaccine-response-may-be-why.html ) , with reference to the study: See mumps immunity waning SciTransMed2018 in dropbox, or DOI: 10.1126/scitranslmed.aao5945). 

Details of the study:

--reviewed specifics of several mumps outbreaks in immunized adults

--data from 6 epidemiological studies of mumps vaccine effectiveness on the past decades in US and Europe

--mathematical modeling done to assess whether this resurgence of mumps outbreaks was related to waning immunity after vaccination or whether new mumps strains emerged not covered by the vaccine

Results:

--immunity persists on average 27.4 years (16.7-51.1) after the receipt of any dose of the vaccine

    --among 96.4% who were expected to get a primary antibody response to vaccination, 25% would lose protection within 7.9 years (4.7-14.7 yrs), 50% within 19.0 years (11.2-35.4), and 75% within 38.0 years (22.4-70.8)

--no evidence that there is a decline in vaccine effectiveness over the years 1995-2006 (ie, it's not that the vaccine just doesn't work as well more recently)

--no evident difference in effectiveness after 1 vs 2 doses of vaccine (ie, same waning immunity from the time of the vaccination, whether the first or the second dose, just that the second dose was given later in life)

    --in 2016, susceptibility of those 10-14yo decreased to 34.8% because of the second vaccine recommendation

--​they estimated that in 2006, susceptibility to mumps infection was 52.8% in those 20-24 yo, 52.6% in those 25-29 yo (this was the beginning of the mumps infection outbreaks); these numbers were 33.8% and 25.2%  back in 1990.  

    --this difference is likely from less long-term effectiveness of vaccine-induced immunity than that from the more robust immune response to natural infection, and the numbers of people getting natural infection has progressively decreased. 

    --most people >65 yo in 2016 had natural immunity, so <10% were susceptible; but 29.2% of those 40-64 were susceptible.

--there are several lines of reasoning suggesting that the outbreaks were related to waning immunity; the most persuasive to me is that if there were an altered and uncovered mumps strain in the vaccine, there should have been mumps cases in the younger age group.  these never happened (in those less than 20 years old, there was no difference in the very high protection rates from the vaccine since from about 1990 until the present).

Commentary:

--prior to vaccination, there were about 186K mumps cases reported every year in the US, >90% occurred in kids by age 20, and there was a 99% drop after vaccination (raising the CDC hope that mumps may be completely eradicated)

--though there have been several recorded outbreaks of mumps in adults in the last several years, cases may well be under-reported since clinicians are not accustomed to consider the diagnosis of mumps in adults and/or report it. 

    --likely even with the typical symptoms: fever, headache, myalgia, fatigue, anorexia; followed by salivary gland swelling/parotitis which can last up to 10 days; less common complications include orchitis, neurologic (meningitis, encephalitis, deafness), arthritis, pancreatitis, myocarditis. but these complications can occur without parotitis, undoubtedly decreasing mumps detection. 

    --and 15-20% of infections are asymptomatic (and this is more commonly in adults). 

    --but adults are more likely to have more severe cases, and up to 10% of mumps infections after puberty have these more severe complications

--outbreak of 317 cases at the Univ of Illinois: all patients had documented 2-dose MMR vaccination, were aged 16-55yo. 3 were admitted to hospital (one meningitis, one suspected meningitis, one for parotitis pain management). 2 had orchitis. the University implemented a third dose of MMR, and their subsequent experience was a sharp drop-off in further cases (see https://www.cdc.gov/mmwr/volumes/65/wr/mm6529a2.htm )

--per their models in the study above, they suggest at a minimum there should be a third dose of vaccine at age 18, though still >50% of adults older than 40yo would be unprotected.  should there be boosters every 10 years?  perhaps we should add in a pertussis booster (since there are pretty common outbreaks of pertussis within only a few years after vaccination: see http://gmodestmedblogs.blogspot.com/2015/03/pertussis-vaccine-not-quite-up-to-snuff.html  and http://gmodestmedblogs.blogspot.com/2015/05/pertussis-vaccine-in-adolescents-and.html  )​

So, 

as of now, it probably does make sense to have booster vaccines to prevent mumps (frequency to be determined). But this brings up a broader issue about vaccines: overall they will tend to have shorter periods of immunity and protection from the virus than natural infections. And even natural infections may need recurrent exposure to the infectious agent to create life-long immunity (ie, the presence of virus in the community might boost and prolong their antibody protection).  so, to me, we need to look at vaccines in terms of their anticipated very long-term effects on the ecology/epidemiology/clinical characteristics of the infection: for those really bad infections in kids, we should certainly opt for powerful vaccines (polio, rubella, pneumococal disease, HIB, etc etc). but perhaps we should be less accepting of vaccines for childhood diseases when the morbidity/mortality is much less than in infected adults: such as mumps or varicella. My real concern with the varicella vaccine 20 years ago was that protecting kids might create a large group of adults who might then be susceptible later on, and varicella in adults is much more likely to be a terrible disease. Fortunately, that has not happened so far. But it really should be part of the vaccine evaluation as to what may be the long-term negative effects (some of which may not be known, since for many childhood diseases, adults rarely got them because of their immunity). vaccines kicking clinical disease down the road may not be in the overall public good, especially given the waning numbers of adults willing to get repeated vaccinations to preserve their immunity (they are not the captive audience of kids going to school).