getting rid of vaccines?????

 

--as we quickly approach the post-science darkening ages, i thought it would be useful to recirculate an old blog on measles. But first, some comments on the anti-vaxxers and polio:

 

    -- per the NY Times: "The lawyer helping Robert F. Kennedy Jr. pick federal health officials for the incoming Trump administration has petitioned the government to revoke its approval of the polio vaccine, which for decades has protected millions of people from a virus that can cause paralysis or death…that campaign is just one front in the war that the lawyer, Aaron Siri, is waging against vaccines of all kinds”: https://www.nytimes.com/2024/12/13/health/aaron-siri-rfk-jr-vaccines.html 

    --it is abundantly clear that the polio epidemic in the US in the 1950s led to both lots of morbidity and mortality back then, that lots of post-polio muscular problems until now, that the vaccine invented then by Jonas Salk dramatically stemmed the virus (providing immunity to all 3 of the poliovirus strains), that polio is still present around the world, and that the globalization that we now live in will reintroduce polio to the US among unvaccinated people in the future:

        -- given that most of us in medicine (and in the general population) do not have any first hand experience with the polio outbreak, there is some pretty great background information regarding the situation in the 1950’s, which had killed or paralyzed over half a million people every year globally, led to the use of “iron lungs” (large units that littered the halls of US hospitals to help afflicted people breathe and survive), and the development of the Salk vaccine that led to shockingly great reductions in polio cases (by 1961 there were only 161 cases): https://www.who.int/news-room/spotlight/history-of-vaccination/history-of-polio-vaccination

        -- post-polio syndrome is a worsening of motor neuron disease after recovery from a polio infection, with 25-40% of those who had fully or partially recovered from polio infection developing increasing disability, mimicking other motor neuron diseases (ALS, spinal muscular atrophy, and primary lateral sclerosis): https://pmc.ncbi.nlm.nih.gov/articles/PMC10123742/

        -- and polio is still present around the world: https://polioeradication.org/about-polio/polio-this-week/

            -- Pakistan and Afghanistan still have native polio cases (wild type 1 polio)

            -- many countries have vaccine-derived poliovirus infections (this was from the live virus oral Sabin vaccine, which led to some relatively small number of cases of a polio syndrome, about 1 in 2.7 million doses of the oral polio vaccine, but this polio unfortunately can spread to other folks who are not immunized): in Algeria, Chad, Ivory Coast, Djibouti, Niger, Nigeria, and Occupied Palestinian territory: https://polioeradication.org/about-polio/polio-this-week/ , and has been found in the US, with a case report in New York state in 2022 (https://www.cdc.gov/vaccines/vpd/polio/hcp/vaccine-derived-poliovirus-faq.html )

                -- the CDC reported this New York case, noting that “A vaccine-derived poliovirus (VDPV) is a strain related to the weakened live poliovirus contained in oral polio vaccine (OPV). If allowed to circulate in under- or unimmunized populations for long enough, or replicate in an immunodeficient individual, the weakened virus can revert to a form that causes illness and paralysis.”, and that those who are immunodeficient “can shed the virus for long periods of time, during which the virus can continue to change and can infect an unvaccinated person”

                     -- of note, the oral polio vaccine (OPV, or Sabin vaccine) was stopped being used in the US in 2000 because of VDPV, with only the injected IPV (Salk vaccine) being used which is not a live vaccine and cannot lead to infections

                    -- that being said, there were still 672 confirmed cases in the first 6 months of 2024: https://www.cdc.gov/mmwr/volumes/73/wr/mm7341a1.htm

 

and, as a recent disaster from the anti-vax movement, the death of many kids in Samoa in 2019, deaths that were influenced directly by  by Robert F Kennedy's anti-vax rhetoric:

-- 2 young children died from measles vaccinations from accidentally contaminated measles vaccines

-- measles vaccination rates in Samoa had been declining from the prior 99% coverage in children, with researchers attributing this decline in part to vaccine mistrust by the population from these 2 deaths: (see measles Samoa outbreak LancetInfDis2020 in dropbox, or Craig AT, Heywood AE, Worth H. Lancet Infectious Diseases 2020; 20(3), 273-275)

-- but this was all reinforced by Kennedy and his group, his having both a well-known name and an anti-vax passion that he shared with Samoa in a visit there (see the timeline: https://www.protectourcare.org/timeline-rfk-jr-s-deadly-visit-to-samoa/ )

-- and this resulted in 83 measles-related deaths from 5707 measles cases (attack rate 285 cases per 10,000 people), 87% of which were in children younger than 5yo with a death rate of 25/100K people that age

-- the NY Times (https://www.nytimes.com/2024/11/25/opinion/rfk-jr-vaccines-samoa-measles.html) had a blistering report on this malfeasance, along with the expected conspiracy theory by a doctor lauding Kennedy's anti-vax movement and considered by Kennedy to be "one of the great leaders" of the anti-vax movement, who stated that the metal used in the Covid shots would make the recipients magnetic, and that "they can put spoons and forks all over them and they can stick"........ 

 

-- which brings us to that measles blog, but first, to review a few things:

    -- several studies have completely debunked the reappearing misinformation that measles vaccine leads to autism, the theme song of the vax-deniers

    -- measles is the most communicable disease known https://pmc.ncbi.nlm.nih.gov/articles/PMC8378671/ ), with the highest R₀ (which became a household word in the covid pandemic, representing the average number of people who would be infected by an index person): https://pubmed.ncbi.nlm.nih.gov/28757186/  :

·         Measles – 12-18.

·         Chickenpox – 10-12.

·         Polio – 10-12.

·         HIV/AIDS – 2-5.

·         SARS – 0.19-1.08.

·         MERS – 0.3-0.8.

·         Common Cold – 2-3.

                             Ebola – 1.56-1.9.

      -- of note here, polio is also pretty bad.....

 

For Measles:

-- a WHO report in 2018 noted the resurgence of measles cases globally in 5 of the 6 WHO regions: https://gmodestmedblogs.blogspot.com/2018/12/measles-increasing.html

-- a CDC report in 2019 found a widespread increase in measles cases to 940 cases in 26 states in the US, mostly in unvaccinated individuals: https://gmodestmedblogs.blogspot.com/2019/06/increasing-measles-and-hepatitis.html

-- and, most scarily, measles infection leads to broader immunosuppression, leading to high levels of non-measles mortality: https://gmodestmedblogs.blogspot.com/2020/02/measles-infection-diminishes-other.html, reproduced below

Here is the blog from 2020, beginning with a prior blog from 2015:

From an older blog on measles (http://gmodestmedblogs.blogspot.com/2015/05/measles-and-immunosuppression.html ), and a subsequent study from 2020 using more advanced techniques confirming that native measles infection (which is unfortunately increasing because of parental declination of kids getting the MMR vaccine) results in "immune amnesia" from prior exposure to an array of prior pathogens. 

--measles remains endemic in most of the world: >7 million get it annually and >100,000 die

--because of reduced vaccination, the number of measles cases has increased in the US close to 300% since 2018

--measles infection is associated with increased morbidity and mortality for as long as 5 years, likely to be explained by the diverse effects of this infection, especially measles-induced immune amnesia

--mass measles vaccination in the past reduced overall childhood mortality by 30-50% in resource-poor countries and up to 90% in the most impoverished countries. this benefit could not be explained simply by preventing measles infection alone.

--measles virus (MV) infection is associated with profound immunosuppression, and recent data challenge the prior notion that this is a transient phenomenon:

    --data (mostly animal) suggest that measles infection leads to a loss in immune memory cells, and that this is prevented by vaccination

    --in macaques, measles infection leads to systemic depletion of lymphocytes and reduced innate immune cell proliferation. MV leads to replacement of "the previous memory cell repertoire with measles virus-specific lymphocytes, resulting in 'immune amnesia' to non-measles pathogens". Recovery of these memory cells requires restimulation by the appropriate antigens

    --in the current study, they looked at 4 sets of data from resource-rich countries with adequate data on the pre- and post-measles vaccination period (England, Wales, US, Denmark) to test the hypothesis that MV infection leads to immune amnesia, findings:

        --there was a significant correspondence between measles disease incidence and mortality overall

        --there was significant reduction in nonmeasles infectious disease mortality associated with the introduction of the measles vaccine (vaccination programs occurred at different times in the different countries, 20 years later in Denmark)

        --the data from England and Wales suggested that the duration of MV-immunomodulation lasted 28 months on average. in the US data it was 31 months, and 30 months in Denmark

            --this time lag was consistent for age groups 1-4 yo and 5-9 yo.

        ​--the increase in mortality was consistent for different diseases (pneumonia, dysentery/diarrhea) and different organisms (bacteria --eg strep, pneumococcus, typhoid, meningococcus -- as well as fungal and viral pathogens), though not so for septicemia and rubella, which seemed to have shorter periods of immunologic amnesia (3 months and 12 months, respectively). this suggests a pretty global immune amnesia.

        --assessing pertussis, which is not associated with immunosuppression, vaccination did not influence non-pertussis mortality in England and Wales

    ​    --one interesting corollary of the above finding is that MV infection could diminish the herd immunity effect (ie, population immunity) from other infections (ie, not only increase the susceptibility of an individual infected with MV to a non-measles infection, but also of a non-measles infection being more likely to spread throughout the population, even to those who did not get MV but are susceptible to other infections). or to put that more concretely, if you need 80% immunity in a community to prevent the spreading of infectious disease XXX, and the level is 90% in that community, a measles outbreak may bring that immunity level down to 50-60%, making the whole community more susceptible to the spread of infection XXX.

 

so, again, the above data challenge the usual (simplistic) understanding about vaccination: its effects are not simply increasing immunity to its targeted specific microbial species, but that any immunologic manipulation may have collateral effects on the functioning of the immune system overall. what are the implications of this? 

    ​-- the reverse could be true: vaccination could conceivably cause profound alterations of the immune system or other systemic effects which mitigate the protection from the vaccine. examples might include the earlier rotavirus vaccine, associated with documented increased risk of intussusception in kids. or even studies from the 1940's finding that there were lasting remissions of autoimmune-related disorders after measles infections. so, it is important to look beyond vaccine-specific clinical benefits but at a much larger picture (such as the overall mortality effects noted in the measles study above)

    -- there also may not be much of a correlation between a robust antibody response and clinical disease protection. for example a recent dengue vaccine achieved robust immunologic response from all 4 serotypes included in the vaccine, but there was no significant clinical protection in those with serotype 2 infection (the most severe serotype).

    ​--and, yet again, this measles article brings up the importance of our always challenging and modifying our understanding of physiologic processes.

--------

The 2020 blog:

a 2019 measles study assessed the effect of measles infection on unimmunized children and noted a profound effect on the antibody titers of many other viral infections (see measles immunosuppression science2019 in dropbox, or Mina MJ Science 2019: 366; 599-606)

Details:

--77 unimmunized kids, mean age 9, who developed laboratory-confirmed measles infection, and 5 unimmunized kids who did not

    --of the infected kids, 34 had mild measles and 43 severe

--blood samples were collected a mean of 10 weeks prior to infection and again a mean of 7 weeks after

--blood was analyzed using VirScan to detect antibodies to many viruses:

Results:

--measles infection was associated with a mean reduction of 20% in the overall diversity of the antibody repertoire measured

    --the effect size varied between individuals: 16% of them lost >40% of their antibody diversity

    --there was no difference in total IgG, IgA, or IgM levels: the researchers suggest that the reason the total IgG is unchanged is because there was a "restructuring of the antibody repertoire after measles"

    --there was a differential effect in the loss of their total preexisting pathogen-specific antibody repertoires, depending on the severity of the clinical measles:

        --mild cases: median loss of 33% (range: 12-73%)

        --severe cases: median loss of 40% (11-62%) 

        --controls: retained 90% of their repertoires, even for those measured after a longer duration

    --the most affected 20% of kids lost >50% of the pathogen-specific antibodies for most pathogens; in some up to 70% loss was found for some pathogens

--they also looked at antibody epitope binding sites by the VirScan, assessing 1100 epitopes (ie, the sites on the antibody that recognizes the antigen), finding that of approx 1100 epitopes assessed:

    --controls: no significant changes

    --after mild measles infection: 12% reduction

    --after severe infection: 39% reduction

--comparing pre- and post-measles infection, they found that enterovirus, RSV, rhinovirus, influenza virus, coronavirus, herpesvirus, papillomavirus, and adenovirus all decreased with high statistical significance (7 of them with p<0.001 and one with p<0.05)

--giving the MMR vaccine did not affect the immune repertoire (ie, the vaccine was safe and did not confer the immunological havoc of the infection)

--epidemiologic investigation suggested that immune repertoire reconstruction was from new exposure to pathogens where the prior immunity was depleted; and that in a few cases cited, this entailed clinically significant infections (eg one kid developed pneumonia). ie, some people needed new exposures to old infections in order to redevelop antibody responses: the immunological amnesia from measles infection really did deplete immune memory from prior infections, with the unsurprising clinical results)

Commentary:

--these studies bring up a few issues:

    --it seems pretty evident that the adverse effects of measles infection are profound and extend beyond the specifics of the measles virus: there seems to be immunologic amnesia to many other infections. and this might well explain the high general mortality both at the time of measles infection and even years after infection (studies in monkeys found that following a measles infection, researchers were no longer able to detect up to 60% of the antibody repertoire, and this persisted at least 5 months)

    --perhaps the safest thing to do after someone gets measles is to revaccinate them with the routine childhood vaccinations (eg, the example above of a kid getting pneumococcal pneumonia)???

--per the CDC, one dose of MMR is 93% effective against the measles, 2 doses are 97% effective (see https://www.cdc.gov/vaccines/vpd/mmr/public/index.html )

--and, measles vaccine-acquired immunity is reported to wane in at least 5% of cases within 10-15 yrs after vaccination, per https://www.nvic.org/vaccines-and-diseases/Measles/measles-vaccine-effectiveness.aspx

--an older study in 1990 looked at antibody response over time to live measles vaccine (the US went to a 2-dose vaccine regimen in kids in 1989). [there is both a cellular and humoral immune response, the latter being much easier to measure]. There are a few caveats here, including that there have been different lab tests to assess the antibody response, the prior studies were done on people with only 1 dose of vaccine, and it is not clear what the cutpoint of antibody response is associated with clinical immunity from the disease (though there is evidence that some people with low quantity of antibody may not be protected, as documented in the article: Markowitz LE. Pediatr Infect Dis J. 1990; 9:101-110)

--there are several immunological diseases associated with a prior measles infection (suggesting its widespread and longstanding generalized immunological perturbations), including postinfectious encephalomyelitis or the later-appearing subacute sclerosing panencephalitis

from the above, perhaps measles vaccination is the most important of the vaccines we can give. ironic that it has been the major one targeted by the anti-vaccine groups....

-- indeed, we are now in for a roller-coaster ride, one with a rickety frame and without guardrails

geoff

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