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Measles gets a helping hand

In a recent post I shared a bit of my personal, near-death experience with measles during the US epidemic of 1989-1991. As I describe in that post, I contracted a very serious measles infection at the end of medical school, and was highly infectious when I interviewed for a residency position at Seattle Children’s Hospital. Like others my age who received an ineffective, killed measles vaccine between 1963 and 1967, I had not been adequately protected. The MMR vaccine was not yet available, and no boosters were recommended at the time. Unfortunately, though my measles titers (a test of immunity to measles) were checked when I entered medical school, the school’s student health department failed to notice or respond to the results – I was not immune and did not receive a booster dose at that time, as I should have. That mistake was huge, and could have cost me my life. It also caused me to potentially sicken many vulnerable children during my tour of the hospital, as well as others I may have inadvertently exposed during the window of communicability as I walked the streets of Seattle. The Department of Health had to be called to trace all of my steps and attempt to track down and protect any potential contacts.

Measles (or rubeolla) is a serious infectious disease caused by an RNA-containing paramyxovirus. The virus is primarily spread by respiratory droplet from a cough. Within two days of replicating in the nose and throat, it disseminates rapidly throughout the body. The incubation period is 10-12 days, after which the clinical manifestations of the disease begin. These early signs typically include escalating fevers, runny nose, cough, and watery, red eyes. Within a few days, the typical pink, blotchy measles rash begins at the hairline and spreads down the body, usually lasting for 5-6 days. While the initial signs of measles (the prodrome) resemble a bad cold, the illness quickly becomes much more severe. As a resident, we were taught that there is no such thing as a mild case of measles. Victims invariably look and feel horribly ill. Additionally, 30% of cases are associated with complications such as diarrhea, ear infections, pneumonia (5%), encephalitis (0.1%), seizures, permanent neurological impairment, and death (0.2%). The highest morbidity and mortality is seen in children under 5 and adults over 20 years of age. The mortality rate is approximately 0.2%, with death usually a result of pneumonia or encephalitis. Subacute sclerosing panencephalitis (SSPE) is a rare, degenerative brain disease that occurs several years following an episode of measles in approximately 5-10 cases per million reported cases.

Prior to introduction of the measles vaccine in 1963, there were approximately 500,000 cases of measles reported annually in the United States, though it is estimated that the true annual incidence was more like 3-4 million. The disease reared its head in 2-3 year cycles, infecting nearly everyone at some point during childhood. Shortly after the vaccine was introduced, the incidence of measles plummeted by more than 98%, and the epidemic cycles ceased.

measles graph

The combined MMR vaccine, covering measles, mumps, and rubella, was introduced in 1971, though still as a single dose. A booster dose at 4-6 years of age was recommended in 1989 when it was determined that over half of all school-aged cases of measles occurred in children who had already been vaccinated. The addition of this second dose for school-aged children raised the vaccine efficacy rate from 90-95% to 99.7%, and in 1983 there were fewer than 1,500 reported cases of measles in the United States. The epidemic that occurred in this country between 1989 and 1991 (my own illness included) resulted in over 55,000 cases and 123 deaths, and was largely a result of poor vaccination rates among black and Hispanic preschool-aged children living in high-poverty, urban areas. Ninety percent of deaths during that epidemic occurred in people who were entirely unvaccinated. A major campaign to vaccinate all preschool-aged children brought this crisis under control, and disease rates have declined since then. In 2000 measles was officially eradicated as an endemic disease in the United States. In 2004, a record low 37 cases of measles were reported, presumably all a result of importation from endemic countries.

Though this is a tremendous accomplishment, the successes achieved throughout the rest of the world are equally if not more encouraging. Within two years of successfully eliminating the transmission of measles in the United States, a relentless vaccination program conducted by the Pan-American Health Organization (PAHO) is close to achieving similar success throughout Latin America and the Caribbean. In 2011, the PAHO asked each member country to submit a progress report to verify the eradication of measles, rubella, and congenital rubella syndrome from the Americas. The CDC has just published this report for the United States, and has confirmed the sustained elimination of these entities. Once the other reports are in, the Western hemisphere will have verified an amazing, widespread public health accomplishment.

Similar successes are being demonstrated around the world. Globally, the coverage rate for the first dose of a measles-containing vaccine increased from 72% to 84% between 2000 and 2011. The number of countries providing a routine second dose increased from 97 (50%) in 2000 to 141 (73%) in 2011. During this period of time, the annual reported measles incidence decreased 65%, from 146 to 52 cases per million population, and the estimated number of measles deaths decreased 71%, from 548,000 to 158,000. All World Health Organization (WHO) regions of the world reported substantial reductions in mortality, ranging from 36% (India) to 90% (Western Pacific). Between 2000 and 2012, an estimated 13.8 million people worldwide were spared a measles-related death due to the Measles and Rubella Initiative, a global collaboration between the WHO and national infectious disease and control agencies. Still, hot regions of low vaccination coverage continue to challenge these efforts. According to the CDC’s report on the Global Control and Regional Elimination of Measles, 2000–2011:

Field investigations of recent measles outbreaks found most cases were among unvaccinated persons, suggesting the main underlying cause was persistent gaps in immunization coverage, despite overall increased measles vaccine coverage…All five countries with the largest number of infants who did not receive MCV1 [a single dose of measles-containing vaccine] through routine immunization services in 2011 had large outbreaks of measles during 2011, highlighting the importance of a strong immunization system.

Here’s where our success story takes a sick and ironic turn. Despite our triumph over these seemingly monumental challenges – dramatic drops in morbidity and mortality in the far corners of India and Africa, and the near heroic success of eliminating measles from places like Mexico City’s Neza-Chalco-Itza, considered the world’s largest slum – our hope of truly eradicating measles from the planet faces an additional but much more banal obstacle: educated, privileged, Google-empowered parents who fall for the pseudoscientific mythology of vaccine risk. Enlarging pockets of underimmunization due to vaccine hesitancy are threatening to derail our massive, worldwide efforts at controlling this and other horrendous diseases.

Vaccine hesitancy and refusal was largely responsible for the 189 confirmed cases of measles that occurred in the United States in 2013, the highest measles rate in 17 years. According to the CDC, most cases were in persons who were unvaccinated.

The trend shows no sign of breaking. Some of the more recent cases and outbreaks in the US highlight this problem:

  • March 13, 2013: Brooklyn, NY – an intentionally unvaccinated 17 year old who became infected with measles while on a trip to London, initiated the largest outbreak of measles in the United States since 1996. A total of 58 cases were identified, all in an orthodox Jewish community of Brooklyn, NY. All cases occurred in intentionally unvaccinated individuals or in infants too young to be vaccinated.
  • April-May, 2013, North Carolina – An unvaccinated traveler to India sparked an outbreak of 23 cases of measles. Most cases were among residents of a largely unvaccinated religious community in rural North Carolina. Most were unvaccinated.
  • August, 2013: 20 cases spread through a Texas Mega-church, the leader of which preached about the dangers of vaccines. All cases occurred in families that chose not to vaccinate, and all of the infected children to had been home schooled.
  • Feb 4, 2014: Measles confirmed in a graduate student at MIT who acquired the disease on a trip to South America.
  • Feb, 2014: Five Counties in New York each reported one confirmed case of measles. Four of the five cases were unvaccinated:
    • Feb 1, 2014: Rennselaer County, NY – A case of measles confirmed in a student at Rensselaer Polytechnic Institute (RPI). Multiple exposures may have occurred in a number of different settings beyond the college campus due to the student’s recent cross-country travel.
    • February 4, 2014, Albany County, NY – An unvaccinated one-year-old child contracted measles on a trip to the Philippines. He was treated and potentially exposed people at a private medical practice and at the Albany Medical Center.
    • February 7, 2014, Rockland County, NY – Another one-year-old unvaccinated child developed measles while visiting the Philippines and potentially exposed patients at a local medical office and a large shopping mall.
    • February 7, 2014, Monroe County, NY – A University of Rochester student who contracted measles during a trip to the Republic of Georgia was treated at Strong Memorial Hospital.
    • Feb 24, 2014: Orange County, NY – DOH issues Health advisory concerning a confirmed case of measles in Goshen, NY.
  • Feb 24, 2014, Framingham, MA: two confirmed cases of measles potentially exposing many people at a Trader Joe’s, a local restaurant, a Bose Corporation office building, and a Harvard Vanguard medical clinic.
  • Jan-Feb, 2014: California – 15 cases of measles have already been documented in California this year, mostly associated with travel to the Philippines and India. Most of the cases occurred in intentionally unvaccinated individuals or in infants too young to be vaccinated. Four of the 15 cases occurred in the Bay Area. This includes an unvaccinated man with measles who rode the San Francisco BART train between Feb. 4 and 7, potentially infecting many people in a particularly underimmunized region.

The human tragedy aside, outbreaks like these require extensive resources from state and local public health agencies, including thousands of hours of investigative labor.

As bad as it is in the United States, the creeping menace of vaccine denialism has taken root even more destructively in the United Kingdom. The UK reported 2,000 cases of measles in 2013, the highest level in 19 years. In the Swansea region of Wales alone, over 1,200 cases of measles were reported between November, 2012 and July 2013, and the numbers continue to rise.

Measles Alert

It is clear that, while we have succeeded in eliminating endemic measles in the US, imported cases from other countries are creating outbreaks in areas where parents are altering vaccine schedules and outright refusing to vaccinate in increasing numbers. As discussed previously, the school vaccine exemption rate demonstrates wide geographic variability, from 0.1% in Mississippi to 6.2% in Washington State. But even this hides more extreme regional differences. There are some schools and school districts with much higher exemption rates and dismally poor vaccine coverage. Washington State publishes its school vaccination and vaccine exemption rates. A quick search of their DOH website reveals countywide exemption rates as high as 19%. California also publishes vaccination and personal belief exemption rates on its DPH website. Perusing this data is truly eye-opening and frightening. In Marin County, 7.8% of kindergarten students have been registered as vaccine-exempt by their parents. Some schools in the state have staggeringly high vaccine exemption rates. There is one in which the entire student body is vaccine-exempt. While vaccine exemption rates can tell us much about the trends in parental vaccine hesitancy, it underrepresents the problem. For example, it tells us little if anything about parents who alter the schedule without claiming a formal exemption. An altered schedule may technically meet school vaccine requirements, while still damaging herd immunity and increasing the population risk of disease.

Although the problem of parental vaccine hesitancy in the United States is of critical public health importance, it’s an issue that has been largely ignored. Parents who are concerned may be hesitant to bring it up, as it tends to polarize individuals within communities. While much emphasis is placed on the safety of our children’s environment, from the air they breathe and the water they drink, to the types of foods they eat and the way their fruits and vegetables are grown, few parents give any thought to whether their children are surrounded by the protective shield of community immunization. While this information should be an important consideration when deciding where to send one’s child to school, it isn’t on the minds of most parents, nor is this information typically made available. My state of Massachusetts does not currently publish this data. None of the parents I know have ever thought about the degree to which their children are protected by herd immunity in their school or community. If that data were made available, and the importance of community immunity discussed and pushed more aggressively by providers, public officials, and society in general, perhaps the dangerous trend of vaccine hesitancy would begin to shift. It would be a tragic shame if all of our efforts and dramatic successes were thwarted by the backward antiscience of parental vaccine denialism.

We have also arranged things so that almost no one understands science and technology. This is a prescription for disaster. We might get away with it for a while, but sooner or later this combustible mixture of ignorance and power is going to blow up in our faces.

- Carl Sagan (from The Demon Haunted World)

Posted in: Epidemiology, Medical Ethics, Politics and Regulation, Public Health, Science and Medicine, Vaccines

Leave a Comment (75) ↓

75 thoughts on “Measles gets a helping hand

  1. Stephen H says:

    I have suggested elsewhere that anyone who chooses not to be vaccinated, or not to vaccinate their children, is effectively choosing to live outside of society. Vaccination is one of the sacrifices one makes to be part of a modern society – it is an obligation placed upon every society member who can possibly be vaccinated to protect those who cannot.

    Children should not be permitted to enter a school (public or private) unless vaccinated. Adults should not be permitted to undertake any of the activities that requires societal bonds: no driver’s licence, no bank accounts, no ability to enter into a contract…

    And of course Andrew Wakefield should be sued on behalf of every child in Britain that has been infected above the pre-scare levels. He and others who make these ridiculous claims should also be subject to court action from those of us who are autistic and our parents, for the pain and suffering caused by blaming their perfectly harmless behaviours for something that is genetic.

    Strangely, I also read someone state that they could not be vaccinated because they are vegan – presumably while ignoring all of the products they encounter every day that are made out of animal but are convenient to the lifestyle.

    /rant off… for now.

    1. WilliamLawrenceUtridge says:

      Vaccination is one of the sacrifices one makes to be part of a modern society

      You should really put “sacrifices” in quotes, since it’s not really a sacrifice. A sacrifice would be daily testing of all humans and shooting the ones who are infected. A year of this and we’d eliminate all communicable diseases. And reduce overpopulation!

      By gumbo my thoughts run in dark paths these days.

      1. Iefske says:

        sounds like a good zombie outbreak approach, but incubation periods and sky-rocketing bullet prices might interfere with your one year estimate…

  2. Lawrence says:

    Jeez – just a simple precaution, such as getting yourself or your family vaccinated before travelling overseas, would have prevented these outbreaks….better yet, are we still requiring proof of vaccinations for international travelers entering the US?

    The anti-vax militia must be proud – their pro-disease agenda is obviously gaining a tiny bit of traction.

    1. “are we still requiring proof of vaccinations for international travelers entering the US?”

      Notice that in the case of measles, nearly all cases in the US trace to unvaccinated American citizens who traveled to areas where measles is still endemic.

      1. TsuDhoNimh says:

        The only true exogenous import I can think of is the Tucson outbreak, which was a Swiss tourist entering during the incubation period.

        The usual cries of “it’s the filthy illegals coming across the Mexican border” are wrong. Mexico is highly vaccinated and their last case of measles was imported from France.

        It’s the people wealthy enough to travel, and foolish enough to thing that they are invulnerable.

      2. John Snyder says:

        An excellent point. Unfortunately, there are currently no vaccination requirements for entry to the United States.

  3. AnObservingParty says:

    Hear hear, Stephen. Like any decision that comes with risk that we are all fully entitled to make, there must be enforced consequences. As an adult, I have every right to imbibe alcohol. But because of the risks to others, I am prohibited from interacting with others in certain ways, such as on roads behind the wheel of a car. This is the same. You have every right to make that decision, but here are the consequences.

    It’s terrifying.

  4. Anna J. says:

    This is really worrying. Since I’m about the same age as the author, I’m wondering if I’ve got any immunity to measles or whether I’m vulnerable. My mother’s a bit fuzzy on the details of my childhood vaccinations so would it be good to be tested or just get the MMR shot?

    1. nancy brownlee says:

      @Anna J
      “would it be good to be tested or just get the MMR shot?”

      Last year I ‘topped up’ all my immunizations- at my local Walgreen’s. I’ve always had a tetanus booster every so often- I was a professional gardener for decades and anyone who gardens even casually needs current tetanus immunization, because the pathogen is soil borne, in animal feces.

      It’s easy and cheap and harmless, even if you already carry some immunity. There’s no reason NOT to.

  5. OGrady_Texas says:

    I was a small child in the days before the measles vaccine was licensed. An asthma sufferer, I developed pneumonia as a complication of measles. I almost died. I still remember the horrifying air hunger. I was lucky enough to avoid deafness, or brain damage, or any other after-effect of measles. Today I try to convince anyone I can that vaccination for measles can spare other small children the terror I experienced.

  6. goodnightirene says:

    At least once a month I run into someone, usually on a casual basis or someone I help with knitting, who although not outright anti-vax, inevitably will ask, “but isn’t it awful to put ALL THAT STUFF into one injection into a tiny baby?” The implication is that the “stuff” is awful “stuff” (toxic!). The last person who said this to me has a son (who also thinks this) who is about to enter medical school.

    This is where Sagan’s prediction has come to pass. The most basic scientific concepts are totally beyond the general public and, increasingly, even many with science/medical education. Sadly, I’m not sure the above mentioned son will be disabused of many of his notions in the course of training.

  7. steney01 says:

    Massively increased access to information/misinformation + everyone is a winner!/genius!/expert! hubris + mistrust = anti-vaccine, anti-evolution, pro-CAM, anti-climate change.

  8. Bogeymama says:

    I have always presumed that I was vaccinated, but dug out my records and was shocked to find it wasn’t on there although my nurse-mother insists that I was. I was born in 1969, and public health doesn’t specifically recommend it for those before 1970 due to the probability that natural immunity had occurred. Just found out that the local public health clinic DOES recommend it in light of recent outbreaks for all health care workers, so I will be getting my MMR done in the next few weeks.

    1. HSR says:

      The MMR shot wasn’t in my records. My mom thinks I got the shot at a public vaccination event of some kind, rather than at the doctor’s office. When I started grad school, I had titers done, which showed immunity to all three, so I had in fact had the shot. Could the same thing be the case for you? At any rate, no harm in getting a booster.

  9. AlisonM says:

    Wait – you can get vaccinations besides flu at the pharmacy? I’m going to have to check that out, because I keep forgetting to call the doctor. I’m 53, and I’m pretty certain that whatever vaccines I got were not as good as what’s available now, and all these people walking around without immunity worries me quite a bit.

    1. nancy brownlee says:

      @AlisonM
      Yes! There are times when some vaccines may not be in stock at a particular pharmacy- high demand during school start-up, etc- but they have most of them available almost all the time. (They will also call you if you’re waiting on a particular restocking.)

      I’m 66, have a mother who insists I had ‘everything’, all the available vaccines -and I caught ‘everything’ anyway. I just figure that at my age immunity may have waned- and the injections are cheap and easy to get. So I did.

  10. Iefske says:

    A few weeks ago I had to treat (he loves treats) my 5 yo son profilactically for whooping cough to protect his then 2-week old sister. He tested negative, but there are more than a dozen confirmed cases at his elementary school, some in his class (in CA; PBE (anti-vax) rate of 5%). These outbreaks are incredibly frustrating and the one good thing that could come from all this is higher vaccination rates due to either measures that make it more difficult to get a PBE, or anti-vaxers perhaps seeing the light.

    I’m a bit pessimistic about the anti-vaxers seeing the light and not just because of their apparent disregard of, or inability to access the science. There is the problem of linking these outbreaks (whooping cough in particular) solidly to lower vaccination rates and the resulting lowered protection of heard immunity. Solidly being the operative word.

    My request to you all: Does anyone know of good information to share that gets the point across (on pertussis in particular) that lower vaccination rates are the root cause of these outbreaks? It would be helpful if the information does not contain sarcasm, which tends to be counterproductive for convincing people.

    I have talked to his school and one of the problems of linking these outbreaks with vaccination rate decreases is that all the positive cases are vaccinated kids. This is fodder for the non-rational anti-vaxers.

    The vaccine, with a protection rate of ~90% is not perfect (perhaps even lower for particular strains of the bacterium, please correct if I’m off on any of the numbers). I’ve tried explaining that, assuming a 100% share-the-cough rate (not unimaginable at a pre-school), 10% of the vaccinated kids should get whooping cough symptoms; This doesn’t mean the vaccine doesn’t work. The PBE parents have to pull their kids from the school during an outbreak (positive cases in their kids classroom), part of the exemption agreement, which explains the absence of reported cases in unvaccinated kids.

    Much appreciated!

    1. Iefske says:

      Btw, thanks for a great article! I’ll start by passing this one along.

    2. WilliamLawrenceUtridge says:

      That’s terrifying, I hope your kids are OK. Pertussis scares the bejebus out of me.

      Paul Offit writes excellent, well-sourced, readable and short (<200 pages usually) books in general, and is also the dude behind the Children's Hospital of Philadelphia vaccines resource pages. Antivaccinationists hate him because he is well-educated on both vaccines and antivaccination tropes. His opinions are often discounted because of “conflict of interest” in that he has co-ownership (? not sure what the term is) for the HiB vaccine and thus stands to profit from its use – which is true, and is also the reason why he has such intimate familiarity with vaccines, their ingredients, and pediatric immunology. Oh, and since licensing the vaccine, Haemophilus influenzae infections have dropped by 99% while autism rates haven’t really budged.

      Herd immunity is covered in the CHOP page in a variety of places (you could start here) as well as Offit’s books (Deadly Choices addresses herd immunity in a couple places). The CDC has a page on pertussis specifically, which talks about herd immunity specifically (here), but it’s a bit cursory.

      Or you can search on SBM, for instance here, here, here, here and I’m sure there’s more (but not necessarily a “nail-on-the-head” page for herd immunity in pertussis specifically.

      1. Iefske says:

        Great links, thanks!!

    3. Sawyer says:

      “The PBE parents have to pull their kids from the school during an outbreak (positive cases in their kids classroom), part of the exemption agreement, which explains the absence of reported cases in unvaccinated kids”

      This pisses me off in more ways than I can put into words. The same people that are ultra-paranoid about the government/schools/hospitals lying to them are taking actions that completely hide very important public health data from government/schools/hospitals. And yet they cling to the delusion that it’s everyone else’s fault when kids get sick. Talk about psychological projection.

  11. jacobv says:

    My sister and I, along with nearly half a million other people in the US, had the measles 1964. We were lucky and did not suffer any after effects (that I’m aware of) or complications. That a parent who would never think of allowing their four year old to stay home alone while they were at work would think it’s okay to play Russian roulette with a dangerous virus is beyond me. Hubris is an amazing characteristic of the human animal.

  12. harriet huestis says:

    I shouldn’t have to be concerned about immunity to measles. I had measles encephalitis at 4 months old. There have been cases where people who had measles in their first year of life get measles again because their immunity was provided by maternal antibodies and the initial case was mild. I did ask my doctor whether I should get the immunizations but he said I would have Been checked when I was pregnant.
    We recently had an outbreak of measles in Southern Alberta. 42 cases brought in by an unvaccinated traveler to the Netherlands. There is a significant population of Dutch Reform Church members. However with vaccination rates in some places lower than 49% , they only account for small percentage of the unvaccinated. Vaccination rates are higher in Calgary and Edmonton, about 90%. There have been individual cases in Calgary brought in by travelers to the Philippines. 3 of the cases in fully vaccinated people. I have repeatedly had to explain vaccine math in highly vaccinated populations. There are sub communities where vaccination rates are lower in the cities, the upper middle class organic eating I am superior types. So an outbreak in the cities is possible. We were lucky the southern Alberta outbreak started in October so it was able to be contained before Christmas break.

    I believe the willfully unvaccinated should be required to carry risk insurance to cover the public health costs of treating and containing the outbreak and the ongoing consequences of those harmed by the disease. I posted multiple times that my single case of encephalitis has cost Alberta taxpayers in excess of $4million and I am on the mild side. I also think there should be limits or conditions on international travel for the willfully unvaccinated. Perhaps a quarantine period or outright ban.

    1. Tsu Dho Nimh says:

      I believe the willfully unvaccinated should be required to carry risk insurance to cover the public health costs of treating and containing the outbreak and the ongoing consequences of those harmed by the disease.

      Excellent idea … a “special hazards” policy.

  13. Lagaya1 says:

    I know when it comes to the United States, we in Hawaii are often considered “other”( and we like it that way), but you should note the two cases of measles seen here this month: http://www.kitv.com/news/health/health-officials-confirm-2nd-hawaii-measles-case/24671422

    The first came from the Philippines in an 11 month old. The second was infected in the doctor’s office used by the first.

    I actually heard on a news report that if you suspect that you have the measles, don’t go to the doctor or the emergency room. Call your doctor instead.

    1. John Snyder says:

      Very good point. Sorry I missed those cases.

    2. lilady says:

      The Philippines are in the midst of a major measles outbreak (2,417 cases, 2013):

      http://www.wpro.who.int/immunization/documents/MRBulletinVol8Issue01.pdf?ua=1

      If you think your child might have measles, do not take your child to a health care facility, without calling first. Most doctors will arrange to see your child after office hours. If you do not have a private physician, call your local health department to arrange for a health care provider to examine and diagnose your child.

      1. harriet huestis says:

        The Philippines was the source for the Calgary cases and the Regina outbreak. An unvaccinated infected baby traveled from the Philippines through Vancouver and Calgary on the way to Saskatchewan. I love our Chief Medical Officer Dr Talbot. First he calls willfully unvaccinated bad neighbours you don’t want to live beside. Then he informs the public that if you are travelling out of country babies as young as six months should be vaccinated for measles.

        1. lilady says:

          Infants 6 months – 11 months of age, should be immunized against measles prior to international travel, according to the CDC:

          http://www.cdc.gov/measles/travelers.html

          That MMR vaccine “doesn’t count”, toward the recommended 2-dose series of MMR vaccine, administered after 12 months of age, with at least a 28 day interval between the first and second dose.

          I love your Chief Medical Officer Dr. Talbot, who takes a firm stance against the parents who opt out of vaccines.

  14. DocBastard says:

    You absolutely nailed it on the head. The benefits of vaccines overwhelmingly outweigh the tiny risks. I’m gratified that there are people like you pushing back against the rising ride of antivax fanaticism.

    Keep up the fight, and keep working to educate the uninformed, underinformed, and misinformed.

  15. TheFlyingPig says:

    Are there any serious risks for an adult who’s unsure of his vaccination history to just get the lot of them??

    1. nancy brownlee says:

      @Flying Pig

      I think the physicians on this site will second me in repeating: VIRTUALLY NO RISKS. Whatever minuscule risks you might find are infinitesimally small, microscopically tiny, compared to the risks you may face if you contract a serious disease for which immunization is readily available- like measles, mumps, rubella, pertussis- as an adult. Plus, just think how stupid you’d feel, lying there desperately ill, thinking, “god, I coulda…”

    2. mriddel@wowway.com says:

      I’m not a medical person, but it seems to me you’d want to see a doctor or vaccine clinic so that you know which vaccines are appropriate for your age, travel requirements, etc. Some vaccines are only recommended if you are over or under a certain age, for instance. Definately a good idea, though, to get on that. Good on you.

  16. Kiiri says:

    To the person up the thread and pertussis – I work for a local public health department and pertussis is continually the most frustrating illness to talk to anti-vaccine wackadoodles about. The old celluar vaccine was spectacularly effective but had side effects (mainly swelling and pain at injection site). So the new acellular vaccine was developed, minimal side effects, but not as good immunity. Since it immunizes against a protein on the surface of the bacteria and recently I saw a paper (and for the life of me I can’t find it) stating that in one study fully 50+% of the pertussis isolates tested didn’t have that protein. So the vaccine was completely ineffective. Plus recent epi research is showing that the immunity from the new vaccine probably wanes a lot faster than previously thought, and a lot of immunized children can carry it and not get really ill but still be infectious. It’s terrible. We need a new vaccine for pertussis. But the MMR is fantastic. I plan to do some research on vaccination rates before it’s time to send the fully immunized little man off to school in a few years.

    1. Sawyer says:

      The situation with the cellular/acellular development is absolutely fascinating, both from a purely scientific level and from a political perspective. Paul Offit gave a short explanation in a Point of Inquiry interview a few months back, though I’m guessing someone can find a more complete explanation if they scour the internet. Public health agencies are in an impossible situation; switching back to a cellular vaccine would give a tremendous amount of ammunition to the antivaxxers, ultimately defeating the entire goal of the switch.

      Too bad there are human lives at stake, because otherwise I would find the situation quite humorous.

      1. ebohlman says:

        What about keeping the acellular vaccine for infants (which is where the most emotional outrage about a switch would be) and going back to the whole-cell vaccine as a booster for adults/adolescents? Seems to me that would hit the “80/20″ sweet spot since one of the big problems seems to be transmission from adults with waning immunity from the acellular vaccine.

    2. Iefske says:

      Thanks. A little disconcerting that the vaccine may perform that poorly. Perhaps the reason the CDC is so hesitant to link the outbreaks to lower vaccination rates.

      Also, there’s a recent paper on how baboons can carry and pass on whooping cough without showing symptoms, while vaccinated with the acellular vaccine you mention.

      Time for a new vaccine it seems indeed….

      1. Tanya says:

        For what it’s worth, it seems to be the same story all over. I live in Slovenia and my vaccinated son got whooping cough 2 yrs ago when he was 7. It went undiagnosed = untreated, though, as I understand, there was precious little treatment to be had at the stage it was confirmed, anyway. Also, due to the vaccination the case was mild (and consequently misdiagnosed at first). His paediatritian told me there were “qute a few” cases like his – no official data as to how much, as far as I know – and that the older the child, the worse the symptoms (so, lucky us …) Also, that the health authorities were apparently looking into giving boosters to kids at 14 yrs old. It’s not happening, though. Crisis ate up the money, I guess … :-(

  17. F says:

    I have wondered about the vaccination status of the children my kids go to day care or school with. A lot. Especially while they were infants and not fully vaccinated yet (MMR etc). Our school says somewhere in the paperwork they would notify us if there in an unvaccinated child in class, but I wonder if they actually care enough to do that. I would very much like it if they had to publish vaccination and exemption rates. At least I’d know what we are getting ourselves into.
    What are the chances that other states put this into law?

  18. Andrés says:

    Leucocyte ascorbic acid concentration doesn’t seem depleted in measles patients but their plasma ascorbic acid one does. From Leucocyte ascorbic acid concentration and plasma ascorbic acid levels in children with various infections (1993):

    In viral infections such as mumps, measles and chickenpox, plasma ascorbic acid levels were found to be significantly below the normal value, while there was no change in the leucocyte ascorbic acid concentrations (P < 0.005, Table 1).

    Ascorbic acid average (standard deviation) plasma concentration was 0.68mg/dl (0.25) in controls and 0.42mg/dl (0.28) in measles patients, both quite far away of the kidney threshold around 1.4mg/dl.

    Ascorbic acid at 250mg/day has already been demonstrated useless as a measles treatment. From Lymphocyte Subsets in Measles (1983):

    Because subset markers could be improved by in vitro treatment with ascorbate, children with measles were treated with 250 mg L-ascorbate/d, and LMF production assessed after 1 and 3 wk. As can be seen in Table III (b), LMF production was improved by 1 wk, but not to a greater extent than in untreated children.

    As far as I can seed Joffe et alter didn’t measured plasma ascorbic acid concentration. Nevertheless they also found ascorbic acid being very effective in vitro:

    Lymphocyte subsets were assessed in patients with measles using the OKT range of monoclonal antibodies. A significant decrease in cells reacting with the OKT3 and OKT4 monoclonal antibodies was observed. When the tests were repeated 3 wk after the acute infection, significant recovery of these subsets was observed. The abnormality in lymphocyte subsets could be reproduced by treating normal lymphocytes with measles virus in vitro. When lymphocytes from patients with measles or when normal cells infected with measles virus in vitro were treated with either levamisole or L-ascorbic acid for 15 min and then retested with the OKT antisera, restoration of the previously depleted OKT3+ and OKT4+ cell population was observed. Ascorbic-acid treatment also, to a certain extent, reversed the inability of measles mononuclear cells to produce lymphocyte mitogenic factor (helper factor for B cells) after pokeweed mitogen activation.

    When cells from patients with acute measles were pulsed in vitro with 10-4M L-ascorbic acid, considerable increase in the OKT3+ and OKT4+ cell populations was observed, with minimal improvement in the OKT8+ population.

    So an ascorbic acid concentration of 0.1mM = 1.76mg/dl seems effective at least in a proxy measurement.

    Let’s go now to the dangerous, outlaw literature on clinical experience. From The Use of Vitamin C as an Antibiotic (1953) by late Dr. Klenner in one of the very few occasions talking about oral-only vitamin C treatment:

    The use of vitamin C in measles proved to be a medical curiosity. For the first time a virus infection could be handled as if it were a dog on a leash. In the Spring of 1948 measles was running in epidemic proportions in this section of the country. Our first act, then, was to have our own little daughters play with children known to be in the ‘contageous phase.’ When the syndrome of fever, redness of the eyes and throat, catarrh, spasmodic bronchial cough and Koplik spots had developed and the children were obviously sick, vitamin C was started. In this experiment it was found that 1000 mg every four hours, by mouth, would modify the attack. Smaller doses allowed the disease to progress. When 1000 mg was given every two hours all evidence of the infection cleared in 48 hours. If the drug was then discontinued for a similar period (48 hours) the above syndrome returned. We observed this off and on picture for thirty days at which time the drug (vitamin C) was given 1000 mg every 2 hours around the clock for four days. This time the picture cleared and did not return. These little girls did not develop the measle rash during the above experiment and although exposed many times since still maintain this ‘immunity.’

    As I see it either high enough frequent doses of vitamin C are effective in measles patients or Dr. Klenner was completely deluded. Checking that a much smaller dose than 1g/4h doesn’t have any effect doesn’t falsify its hypothesized effectiveness at higher doses. Only when ineffective or toxic vitamin C doses are ridiculous.

    I personally wouldn’t risk any child skipping vaccination though since you don’t know where he/she is going to be when catching the virus and if vitamin C treatment is going to be available/permitted. Moreover, although very unlikely in my view perhaps Dr. Klenner was wrong and the time finally comes when his hypothesis is properly refuted.

    1. Andrey Pavlov says:

      As I see it either high enough frequent doses of vitamin C are effective in measles patients or Dr. Klenner was completely deluded.

      LOL. Seriously Andres? You really, really are stuck on this VitC thing, aren’t you?

      This is one of the most unconvincing pieces of “evidence” you have put up so far. You do realize that this is not even an actual study or itself original scientific research? It is a narrative describing the findings of a very small case series as reported by the investigator experimenting on his own children. It is a few anecdotes from someone who himself was obviously already convinced VitC should work some wonders and was angry that monkey trials showed no benefit, arguing that they are fundamentally different for VitC. He may actually be right about that but it shows his bias.

      And on top of all that, it doesn’t actually demonstrate anything beyond – at best and generously – that it can modulate the syndromic signs of the disease. It doesn’t tell us that they didn’t still have the potential for the negative effects of measles, such as death (the sample size was too small to see if it actually had any effect on mortality), encephalitis (same reason, too small), vision loss, SSPE, etc etc. So even if I could take it entirely at face value, it doesn’t actually show us much.

      AND…. can’t even really do that since they admit later on in the paper that the tests they used to confirm that there was actually measles and not something else could not be trusted which they only learned 6 months later. But still decided that their results were valid.

      Sorry Andres, you keep digging as hard as you possibly can for this VitC axe you have to grind and keep tossing up some really poor “evidence.”

      1. Harriet Hall says:

        Yes, that paper is not acceptable as evidence for several reasons. Anecdotal reports, clear bias on the part of the observer, no firm diagnosis of measles, measles without rash is very rare, measles symptoms don’t last a month, and the cases are said to show the antibiotic effect of vitamin C but measles is a viral disease. Also, it was published in 1953 and no similar cases have been reported in the ensuing 60 years.

      2. WilliamLawrenceUtridge says:

        Andrey, don’t be inaccurate. He’s also got a fetish for vitamin D.

      3. Andrés says:

        Dr. Pavlov said:

        LOL. Seriously Andres? You really, really are stuck on this VitC thing, aren’t you?

        I wouldn’t be so quick laughing at another MD experience but it is just me and I am not one. Around here I know dangerous “in my experience” interpretation wins. I am much more afraid of just ignoring promising therapies instead of them being properly refuted. While Dr. Klenner’s vitamin C experience driven hypothesis keeps being unfalsified I will keep proceeding as it is correct since it seems that we (me and those around me) keep getting positive results. In that sense I am stuck.

        Dr. Pavlov said:

        It is a few anecdotes from someone who himself was obviously already convinced VitC should work some wonders and was angry that monkey trials showed no benefit, arguing that they are fundamentally different for VitC. He may actually be right about that but it shows his bias.

        Everyone has his/her own biases. I actually disagree in his blaming of Dr. Sabin for failing in the replication of Dr. Jungeblut’s experiments as I have said elsewhere (I usually used my name spelled backwards at fora: Serdna) and I personally think the “blame” is on the first series of experiments by Dr. Jungeblut perhaps due to using the subcutaneous route. Yes, I know that those experiments are discordant with everything else I have read about vitamin C parenteral administration and that seems the only difference although I don’t know if it is relevant. Ideally we would have them repeated with intramuscular injections.

        Dr. Pavlov said:

        AND…. can’t even really do that since they admit later on in the paper that the tests they used to confirm that there was actually measles and not something else could not be trusted which they only learned 6 months later. But still decided that their results were valid.

        I am unable to find that passage. It seems to me that Dr. Klenner was convinced it was measles from the presence of Koplik’s spots.

        Dr. Pavlov said:

        Sorry Andres, you keep digging as hard as you possibly can for this VitC axe you have to grind and keep tossing up some really poor “evidence.”

        Of course each piece of data taken by itself doesn’t amount to much. Except the ICU intervention by the Vanderbilt University group with its OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group that I have already pointed out. Yes, it is an afterwards subgrouping but I think there is a reason for its higher effectiveness embedded in the article (it would require confirmation from the authors though).

        @Dr. Hall: I think that Koplik’s spots and being in an measles epidemic was sufficient in Dr. Klenner’s view. Both rash absence and strange duration may be due to the vitamin C intervention. I don’t know if back in 1953 they considered virus alive enough in order to use antibiotic instead of antiviral (I don’t think the semantic objection is relevant in the least though). Of course after the vaccination was common practice there was little interest in vitamin C effectiveness.

        @WLU: As I have already stated my fetishes include iodine too. For completeness I think vitamin K2 and magnesium are quite important too.

        1. Harriet Hall says:

          “Both rash absence and strange duration may be due to the vitamin C intervention.”

          That’s a real stretch! It “may” be due to anything.
          It “may” be due to the barometric pressure or to a genetic anomaly.
          I think it’s far more likely that it may be due to the fact that the symptoms he observed (at least in the latter part of the month) were not due to measles.

        2. Andrés says:

          @Dr. Hall: Of course the latter is another plausible explanation. Once there are populations skipping vaccination it would be ideal if the experiment got replicated in adults.

        3. WilliamLawrenceUtridge says:

          Yes Andres, you have many inexplicable theories that are not embraced by real experts on the topic. It is one of the reasons I don’t respect you.

        4. Andrey Pavlov says:

          I wouldn’t be so quick laughing at another MD experience but it is just me and I am not one.

          Interesting how you have so much respect for someone with certain letters after their name who wrote an anecdotal case series 70 years ago, but don’t afford the same amount of respect to others with the same letters who know much more than that physician did 70 years ago and have access to much more and much better evidence than he did.

          But seriously, can you imagine if I included a reference like that in the article on sepsis I am writing? What sort of place would that have in the echelons of evidence on the topic? That’s why I laughed – not at the physician writing the anecdote. At the fact that you are so committed to proving to yourself and anyone who will listen that VitC is a panacea that you would dredge up that and offer it as “evidence” to support your claim.

          Maybe it was the phlogiston and N-rays that actually helped with the measles? You do realize that much more rigorous scientists have done much more rigorous scientific experiments and been fooled, right?

          Of course the latter is another plausible explanation.

          It is not just another plausible explanation, it is the most probable explanation. At least to people like ourselves with MD after our names and an unbiased view of the evidence base for VitC.

          I am much more afraid of just ignoring promising therapies instead of them being properly refuted

          Is there an emoticon for incredulous exasperation?

          There are limitless conceivable possible therapies. Perhaps in the 1950′s this one might have been considered promising. It is not a promising therapy! We know enough know that while yes, hypothetically there are some uses of VitC that we don’t know of yet that could be maybe worth exploiting no reasonable person with any knowledge on the topic could possibly call it promising. That is your bias showing through Andres. It only appears promising to you because you have already decided it is promising and are trying to fit evidence into that conclusion. That is backwards. It is the precise opposite of how science works.

          If you had never heard of VitC before you could not possibly convince me you would find that article and conclude from it that it is a promising therapy unless you truly had no idea what you are doing…. hmmm…..

          Yes, I know that those experiments are discordant with everything else I have read about vitamin C… and that seems the only difference although I don’t know if it is relevant

          THIS! For the love of sweet baby raptor Jesus, this! This is precisely why it is not a promising therapy! You don’t know if it is relevant, but you assume it is and bias all your reading based on that. How about listening to the bunch of actual MDs and researchers right here on this blog who have told you the answer to that question many times?

          I am unable to find that passage

          First paragraph of page 77.

          We reported in 1951 and 1952 that a constant laboratory fi nding in virus infections was a positive, qualitative Benedict’s reaction. It is necessary to make a correction of that fi nding. This Benedict’s reaction was based on the admission urine specimen of patient’s admitted to our local hospital. About six months ago it came to my attention that this particular urine specimen is collected anytime from the admission of the
          patient to the hospital until some 18 hours thereafter. This, obviously, nullifies the laboratory report since medication given to the patient in the interim would alter the chemical fi ndings. Vitamin C being a powerful reducing agent could account for some of the Benedict urine reports. It, therefore, makes void the contention that this laboratory test is an index when to discontinue the use of vitamin C. The deduction, however,
          is correct

          Kind of a big confounder in their data, there Andres.

          It seems to me that Dr. Klenner was convinced it was measles from the presence of Koplik’s spots.

          You don’t need to link me to the wikipedia for Koplik’s spots. Anyone who graduated medical school should know what Koplik’s spots are. They should also know that they alone are not pathognomonic for measles since they can be confused for other findings on the buccal mucosa.

          Of course each piece of data taken by itself doesn’t amount to much.

          Yes, and in aggregate they don’t amount to much more. GIGO. Garbage In, Garbage Out. You can’t aggregate a whole bunch of crappy data and make it good data. But you just cannot seem to understand how significant figures and the accuracy of measurement affect computational outcomes, so I am not holding out hope you will understand this either.

          You are even taking completely disparate data on processes and pathologies that are only barely tangentially related at best and trying to smoosh them together into some kind of evidence that VitC… I dunno. I don’t even quite get what your point is about VitC except that it isn’t studied enough for your liking since you are so convinced it is a “promising therapy” for all sorts of random stuff.

        5. MadisonMD says:

          @Andres: You are always polite and thoughtful. But I have to agree with Andrey here. I think your ideas are inexplicably misguided. You put so much reliance on a vitamin which has already been put to dozens and dozens of tests over the past 50+ years with no conclusive evidence that it is useful as anything but an anti-scorbutic… yet you reject well-established effective interventions and screening tests because the NNT is too high?

          Well, we don’t even have an NNT for Vitamin C for any condition except scurvy. It could be infinite for all we know. So your I can only explain your position, Andres, by assuming they are fundamentally based on the naturalistic fallacy.

          Do you reject the idea that we could advance medicine more quickly if we stop studying vitamins– already tested extensively– and start testing new things? As I have already said, there are almost an infinite number of possible interventions so testing vitamins again and again wastes opportunities for new discovery.

          In short, we should not invest resources in ruling out every possible application of vitamin C when, instead, we could use the resources to sift through tens of thousands of possible interventions to identify those with more promise. There is a tremendous opportunity cost in the exhaustive research you propose to rule out every possible application of Vit C.

        6. Andrés says:

          WilliamLaurenceUtridge said:

          Yes Andres, you have many inexplicable theories that are not embraced by real experts on the topic. It is one of the reasons I don’t respect you.

          I am curious. How do you define “real experts“? From what I have gathered the common position is just rationalizing why intravenously delivered gram doses of vitamin C are ridiculous and from there forward just ignoring the scant evidence there is about intravenously injected vitamin C in gram doses. By the way, I am talking about infectious diseases not cancer.

          I understand why medicine has established a rank of evidence in order to make decisions. It would be almost perfect if it was coupled to the promotion of experiments designed to refute critiques. Nevertheless experiments are in an almost complete way focused on profit returning inversions. The “almost” part perhaps guarantees that evidence based medicine will slowly converge to the optimum treatments. I don’t like the pace though.

          Dr. Pavlov said:

          Interesting how you have so much respect for someone with certain letters after their name who wrote an anecdotal case series 70 years ago, but don’t afford the same amount of respect to others with the same letters who know much more than that physician did 70 years ago and have access to much more and much better evidence than he did.

          I am certain I didn’t disrespect you in any way except in being stubborn enough to not be convinced by each and every one of your statements. My questioning of usual conclusions seems a fault serious enough to merit your very loose use of the JAQing off term:

          “Just asking questions” is the attempt to make wild accusations acceptable (and not legally actionable) by framing them as questions rather than statements.

          I state “my” hypothesis up front, I am not accusing anyone of anything. About the other proposed meaning:

          2. asking questions and ignoring the answers.

          I must point out that I don’t ignore your answers. What I don’t do is being automatically convinced by your interpretation of the facts.

          Just to clarify I have presented two hypothesis about vitamin C antiviral and antibiotic effect. The first based mainly on Dr. Klenner’s clinical experience:

          1) Intravenous/intramuscular vitamin C in high doses (let’s say 400mg/kg per day) is an effective viral intervention.

          Any experiment focused on falsifying it would refute Dr. Klenner’s results too. Since that is not being studied at all (if anyone has access to much better evidence encompassing negative intervention trials of injectable vitamin C at doses higher than 3g/day either in viral or bacterial infections, please point them out) I have proposed a more humble hypothesis:

          2) Replenishment to normal physiological level (let’s say 60μM) in those patients with measured low ones brings up a positive effect.

          Vanderbilt University group ICU intervention supports this latter point. I used to think a proper (and cheap) RCT was possible in the ICU setting before reading your (Dr. Pavlov’s) take on the matter. What I really don’t understand is why the intervention by Dr. Collier et alter is not being replicated yet. Of course the signal is much more weaker in less serious illnesses and perhaps it is not even there.

          Dr. Pavlov said:

          But seriously, can you imagine if I included a reference like that in the article on sepsis I am writing?

          Of course not. What I am curious about is how do you rationalize to keep skipping over the OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group of the Vanderbilt University intervention. Not that it proves anything being a post hoc analysis but it certainly should inspire curiosity at least and drive someone to replicate it. I am supposing that you are not considering garbage their work.

          Dr. Pavlov said:

          If you had never heard of VitC before you could not possibly convince me you would find that article and conclude from it that it is a promising therapy

          Personally my present strategy acting on vitamin C as if it were an effective antiviral and antibiotic in high enough doses doesn’t mean that I am either closed to refuting evidence or falsely convinced that it has already been proven. I am perfectly aware that my experience is only anecdote that could be explained also by self-limiting illnesses and regression to the mean as unlikely it is in my view since it keeps bringing up consistent results. What I am certain enough is about its powerful antihistamine and antipiretic effect. I don’t remember how much books and papers I had already read when I decided to experiment with vitamin C upon myself. Certainly I had read not only Stone’s book and late Dr. Cathcart’s approach but also the critiques by late Charles W. Marshal and Dr. Barret that I have commented upon before. Since then I have read more including Dr. Levy’s book and Hickey’s and Roberts’ one. I have read several of their referenced papers too.

          When I said:

          Yes, I know that those experiments are discordant with everything else I have read about vitamin C… and that seems the only difference although I don’t know if it is relevant

          I was referring precisely to the initial experiments by late Dr. Jungeblut. Dr. Klenner observed:

          Induration (only when intramuscular injections are given too close to the surface)

          so perhaps using the subcutaneous route impeded good absorption of high doses in Dr. Jungeblut’s experiment. Dr. Pavlov said:

          This is precisely why it is not a promising therapy! You don’t know if it is relevant, but you assume it is and bias all your reading based on that. How about listening to the bunch of actual MDs and researchers right here on this blog who have told you the answer to that question many times?

          I certainly don’t know if it could be relevant although no one has said anything about it yet although I am certainly interested in that piece of information. On the other hand if you are referring to the question “is vitamin C effective as antiviral at high doses?” I am not interested directly in an answer (I know that you think it isn’t) but in experiment data showing that its effectiveness has been refuted.

          Dr. Pavlov said:

          But you just cannot seem to understand how significant figures and the accuracy of measurement affect computational outcomes, so I am not holding out hope you will understand this either.

          I have one last time tried to explain why your argument is wrong back in that thread and failed.

          MadisonMD said:

          You put so much reliance on a vitamin which has already been put to dozens and dozens of tests over the past 50+ years with no conclusive evidence that it is useful as anything but an anti-scorbutic…

          I have already pointed out to its natural history that grants studying it in intravenously delivered gram doses. I have already pointed out to positive results on guinea pigs and rabies (gross estimation of the probability of 17 or less of the 48 guinea pigs in the treatment group dying and 35 or more of the 50 controls dying supposing it being completely by chance —supposing probability of a death being 52/98— is 0.01%) that is still unrefuted. I have already pointed out to the scant intravenous vitamin C interventions that I am aware of. Where is the falsifying evidence?

          MadisonMD said:

          In short, we should not invest resources in ruling out every possible application of vitamin C when, instead, we could use the resources to sift through tens of thousands of possible interventions to identify those with more promise. There is a tremendous opportunity cost in the exhaustive research you propose to rule out every possible application of Vit C.

          I must disagree. I am not talking about “every possible application”. I am talking about its potential antiviral and antibiotic properties at gram doses by intravenous route. I don’t see any “tremendous opportunity cost” in replication of the already positive Vanderbilt University intervention: OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group (post hoc).

          1. WilliamLawrenceUtridge says:

            I am curious. How do you define “real experts“?

            Cancer researchers and academics who conduct clinical trials of, conduct meta-analyses on, and write systematic reviews, of chemotherapeutic agents. Ditto for those who study vitamin C as a career.

            From what I have gathered the common position is just rationalizing why intravenously delivered gram doses of vitamin C are ridiculous and from there forward just ignoring the scant evidence there is about intravenously injected vitamin C in gram doses. By the way, I am talking about infectious diseases not cancer.

            Emphasis added – “scant” means confidence is not justified (and since what scant evidence we have is absurdly unpromising, shouldn’t we turn the limited resources available to us towards something else? Merely because vitamin C is an essential nutrient does not mean it is magical. It is akin to noting that water is essential for life, then leaping to the conclusion that it also must therefore cure cancer).

            I understand why medicine has established a rank of evidence in order to make decisions. It would be almost perfect if it was coupled to the promotion of experiments designed to refute critiques. Nevertheless experiments are in an almost complete way focused on profit returning inversions. The “almost” part perhaps guarantees that evidence based medicine will slowly converge to the optimum treatments

            Merely because a medicine produces a profit for a company does not make it bad, unsafe or ineffective. The reality is most medications will have adverse effects and risks because the human body is not a designed organism, it is a product of messy evolution. And experiments do test novel hypotheses, that’s rather how peer review at the funding stage works – an explicit part of application reviews is the novelty and clarity of the hypothesis. Industry is far, far more concerned with pure efficacy, but that doesn’t mean that their primary driver isn’t hypothesis testing.

            Medical research is expensive and time consuming because biology is complicated. Replacing that expensive, time-consuming process by pushing more speculative ideas into early clinical trials or (FSM-forfend) treatments is a terrible idea. Medicine grinds slow, but it grinds fine, and the results are conclusions that we can rely upon with high certainty. Speeding that process up does not guarantee (in fact it probably obviates) better outcomes.

          2. MadisonMD says:

            @Andres: I was unclear. Let’s recap.

            Andres said: ” I don’t see any “tremendous opportunity cost” in replication of the already positive Vanderbilt University intervention: OR of 0.24″
            I said: “I would absolutely object to replicating the Vanderbilt study. However, I would not object to testing the hypothesis generated by it in a proper prospective RCT, based on this preliminary data. ” (italics added)
            Andres said: “Please, elaborate. I don’t know if you are aware that the intervention seems highly effective.”

            So I said this because your cited Vanderbilt study is a retrospective cohort design. It is not worth replicate since that would use the same design. It would be best to eliminate bias using a RCT design (which I would not object to given preliminary evidence). [Yet, even then the results would not be definitive because alpha=0.05, 1-beta=0.8, and because with a positive trial, the posterior probability of the hypothesis is still not high without a specific mechanism and patient population selected to match that mechanism.]

        7. MadisonMD says:

          @Andres

          I must disagree. I am not talking about “every possible application”. I am talking about its potential antiviral and antibiotic properties at gram doses by intravenous route. I don’t see any “tremendous opportunity cost” in replication of the already positive Vanderbilt University intervention: OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group (post hoc).

          I can’t really understand you here. I would absolutely object to replicating the Vanderbilt study. However, I would not object to testing the hypothesis generated by it in a proper prospective RCT, based on this preliminary data. If positive, I would seek research evaluating mechanism so it could be applied to other situations where it would have value.

          Yet this RCT would not test your hypotheses about antiviral and antibiotic properties of Vitamin C. In fact, exactly which virus and bacteria are we speaking of?… because there are a hell of a lot out there, and it would require exhaustive research to rule out all of them!

          I understand why medicine has established a rank of evidence in order to make decisions. It would be almost perfect if it was coupled to the promotion of experiments designed to refute critiques.

          You underestimate how difficult it is to prove a negative. For example, lets say we run your prospective RCT of IV Vit C in ICU with alpha = 0.05 and 1-beta = 0.8 (fairly standard). Say we do not detect a difference in outcome in the two arms. Well, given statistical power, there is 20% chance this is a false negative. Moreover, you or others could argue that the dose was inadequate, the schedule was wrong, the patients were not sufficiently ill, the patients were too ill, the patients weren’t elite athletes, they didn’t actually have a virus, etc., etc. etc. You could then perform a post-hoc subset analysis and find that, for example in women who had abdominal surgery, there was better outcome with Vitamin C… then demand this be followed up with another RCT. It never ends. You can’t prove the negative. But you do need to stop throwing good money after bad at some point and move on to more promising scientific frontiers. We could reopen the Vitamin C question when a lab researcher delinates a specific mechanism by which vitamin C modulates loading of a nucleic acid into a particular virus capsid. Then we could target the RCT to testing this particular virus and not deal with the shot-gun vitamin approach using poorly powered human studies lacking high prior plausibility.

          Nevertheless experiments are in an almost complete way focused on profit returning inversions.

          I think you are misguided here. Recall that Vitamin E was carefully tested for Alzheimers (covered on SBM), even though there is no money to be made. This is only one example belies the idea that research is only done on profitable therapies. But we could agree that government and private foundation funding of research are crucial to avoid research-for-profit as the only avenue of scientific inquiry.

          I think you should read a bit more widely beyond vitamins about other promising therapies. Could I recommend you read about imatinib, about HAART drug discovery, about the remarkable progress in melanoma treatment with RAF inhibitors and anti-PDL1 antibodies?

        8. Andrés says:

          WLU said:

          Cancer researchers and academics who conduct clinical trials of, conduct meta-analyses on, and write systematic reviews, of chemotherapeutic agents. Ditto for those who study vitamin C as a career.

          Well, for me those are Dr. Hemilä, Hickey and Roberts.
          MadisonMD said:

          I can’t really understand you here. I would absolutely object to replicating the Vanderbilt study.

          Please, elaborate. I don’t know if you are aware that the intervention seems highly effective. That OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group (post hoc) was the same either adjusted or unadjusted. The OR for global risk of dying was OR 0.70 (95%CI 0.56-0.88) before adjustment and OR 0.32 (95%CI 0.22-0.46) after. We are not looking at a non effective intervention we must repartition creatively in order to let it look positive. As I have already stated I think there is a reason for the higher effectiveness on the Expected Deaths group embedded in the article (it would require confirmation from the authors though).

          Since ICU CRTs are going to be quite rare given the reasons estated by Dr. Pavlov /> I would think desirable the intervention to be at least replicated. I don’t know if you are aware of the implicit block there.

          Certainly we are still discovering new actions on the immune system of the vitamin C and still trying to understand how does it works in another ones already known. I don’t think waiting to have a perfect knowledge of its workings is a good idea. Most drugs are not treated so.

          MadisonMD said:

          I think you are misguided here. Recall that Vitamin E was carefully tested for Alzheimers (covered on SBM), even though there is no money to be made.

          Yes, that’s in the “almost” part.

          MadisonMD said:

          I think you should read a bit more widely beyond vitamins about other promising therapies.

          I have already conceded that vitamin C has not a strong effect on cancer.

          1. MadisonMD says:

            Andres– Threading fail. I’ve replied to your note here.

          2. WilliamLawrenceUtridge says:

            Well, for me those are Dr. Hemilä, Hickey and Roberts.

            Why hasn’t the scientific community found their reasoning and results compelling? Why did Hickey and Roberts have to self-publish their book, and why does that book rely on the authority of Linus Pauling rather than firm data? Why did Hemilä have to retract a paper on the topic recently (actually, that’s not really fair since the problem was with their data set and the retraction appears to be an honest, good-faith effort). Why put so much effort into meta-analyses with tiny ns rather than basic data?

            It just doesn’t look promising to me, and efforts to skip over the kind of early work in an effort to push on human trials leaves a bad taste in my mouth. The scientific community is consistently underwhelmed – not because of prejudice, but because of unconvincing data.

            Vitamins aren’t magic.

        9. Andrés says:

          MadisonMD said:

          It would be best to eliminate bias using a RCT design (which I would not object to given preliminary evidence).

          No doubt.

          MadisonMD:

          [Yet, even then the results would not be definitive because alpha=0.05, 1-beta=0.8, and because with a positive trial, the posterior probability of the hypothesis is still not high without a specific mechanism and patient population selected to match that mechanism.]

          Well, I think the effect will be higher if they restrict to either intravenously or intramuscular vitamin C since that is what is observed elsewhere. I have already talked about several actions of vitamin C on the immune system some very recent discovered. These effects give high enough prior probability to the hypothesis in my eyes.

          WLU said:

          Why hasn’t the scientific community found their reasoning and results compelling?

          Well, Dr. Hemilä has written a very complete overview about it.

          I would add that it is not useful to dismiss all the animal experiments when dealing with shared endobiotic substances.

          WLU said:

          Why put so much effort into meta-analyses with tiny ns rather than basic data?

          It wouldn’t be my strategy.

          WLU said:

          Vitamins aren’t magic.

          I certainly haven’t said they were.

          I am curious. Have you read by yourself the already positive Vanderbilt University intervention bringing up an OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group (post hoc)? No, not a CRT.

          1. MadisonMD says:

            Hi Andres,
            Prior plausibility would be higher if you were able to select an appropriate subgroup of patients with a specific diagnosis rather than IV vitamin C to everyone admitted to surgical ICU. Although there is a purported mechanism, it lacks this type of specificity which is usually used to design a confirmatory RCT.

          2. WilliamLawrenceUtridge says:

            I would add that it is not useful to dismiss all the animal experiments when dealing with shared endobiotic substances.

            You might have a point were it not for the fact that humans are very close to unique in their inability to synthesize their own vitamin C.

            I am curious. Have you read by yourself the already positive Vanderbilt University intervention bringing up an OR of 0.24 (95% CI 0.15-0.37, P < .001) for the Expected Deaths group (post hoc)? No, not a CRT.

            Just skimmed the abstract. Interesting. Completely inapplicable to infectious disease, but certainly there is biological probability to support the need for vitamin C in people needing to build and repair substantial amounts of new tissues.

            Also, as usual – if the data is so convincing, why hasn’t it convinced? The apex of medical research is controlled trials in humans in which specific interventions are tested in specific patient groups. Everything else leading up to that apex is suggestive, not indicative.

            What you’ve got, Andres, is an interesting starting point and series of logical deductions and premises leading to a conclusion. That conclusion is not foregone and is only true if every single one of those deductions and premises are true. You only know if they are true by testing them. Leaping to human trials or dogmatic conclusions is premature.

          3. Andrés says:

            MadisonMD said:

            Prior plausibility would be higher if you were able to select an appropriate subgroup of patients with a specific diagnosis rather than IV vitamin C to everyone admitted to surgical ICU.

            I think the effect is strong enough in the Expected Deaths group to grant doing the RCT first and try to pinpoint the mechanism afterwards. For example, as I have already said we know about the regulation of neutrophil extracelular trap (NET) formation by vitamin C only since 2011.

            WLU said:

            You might have a point were it not for the fact that humans are very close to unique in their inability to synthesize their own vitamin C.

            I suppose you are referring to terrestrial vertebrates. Results of ascorbic acid supraphysiological doses are consistent all over both those vertebrates synthesizing it and those vertebrates and invertebrates not doing it as I have already pointed out.

            WLU said:

            Also, as usual – if the data is so convincing, why hasn’t it convinced?

            My preferred hypothesis is that almost everyone is convinced that ascorbic acid is just a simple vitamin coupled with an artificially imposed restriction on their scope to almost only RCT human trials.

            Finally, I have failed to arouse enough curiosity about the results of the Vanderbilt study on the Expected Deaths group.

            First, there has been a letter from Dr. Hemilä pointing out an error in the decimal point placement for the NNT numbers given in the article and confirmed by the authors. The unadjusted NNT is 42.7. The adjusted one is 17.10. Both the adjusted and unadjusted NNT for the Expected Deaths group should be 2.13, that is, the RR is 0.47 in this group.

            Second, Dr. Collier et alter paper estates (my bolds):

            Ascorbic acid was administered as a bolus over 1 hour (0600-1400-2200 time schedule) and selenium as a bolus over 2 hours (1000 time schedule), although both were permitted to be changed to an enteral dosage form once enteral access was established.

            I have already pointed out that the blood concentration attained by oral ingestion is completely different than by intravenous route.

            I will write to the corresponding author about these two points. If the answer lines with my thoughts I will repost it here. If not I will ignore it. Just kidding. I will link to this comment just in case he prefers to answer around here.

            1. WilliamLawrenceUtridge says:

              Hi Andres,

              It’s great that you’ve done all this research and minutely scrubbed through any and all comments for all errors great and small. But I won’t be convinced by single studies. I can never be convinced by single studies, I’m uninterested in them, lack the expertise to interpret them, and don’t have any time or incliniation to acquire that expertise. Instead, I rely on consensus statements and trust the medical establishment to adopt improved practices as time passes.

              When there is a consensus statement indicating megadoses of vitamin C is a good thing for a specific condition, then great! You can gloat all you want (and I’ll point out that this is a single condition and thus an indication for little else). Medicine will improve, suffering will be reduced, lives will be extended. But bickering and peppering me with citations won’t make me care or cause me to adopt the belief that high doses of vitamins are magic or a universal (or even a general) good.

              But please feel free to continue nit-picking and quoting yourself.

            2. MadisonMD says:

              I think the effect is strong enough in the Expected Deaths group to grant doing the RCT first and try to pinpoint the mechanism afterwards.

              Not a good idea. You should always test a hypothesis based on preliminary evidence and mechanism. If the hypothesis is that ascorbate assists healing, then you would select patients who have large wounds and your endpoint might be time to healing by some definition. If the hypothesis is that it helps with infection, then you would select patients at highest risk and your endpoint would be rate of documented infections.

              If you don’t have a hypothesis, then you have many patient characteristics and many endpoints. Your false positive rate skyrockets.

              Yes you could use death as primary endpoint and not worry about the secondaries and mechanism. However, your proposed RCT is only powered at 80% so if you take all comers and detect no difference, do you reject your hypothesis with the 20% false negative rate?

              In short, RCTs are a very bad way to go hypothesis hunting.

            3. Andrés says:

              WLU said:

              Instead, I rely on consensus statements and trust the medical establishment to adopt improved practices as time passes.

              Certainly your choice.

              MadisonMD:

              Yes you could use death as primary endpoint and not worry about the secondaries and mechanism. However, your proposed RCT is only powered at 80% so if you take all comers and detect no difference, do you reject your hypothesis with the 20% false negative rate?

              I expect the effect to be big enough so a small RCT on an Expected Deaths group could be powered at more than 80%. I would have liked to do the numbers with more information about the Vanderbilt study since I suspect the effect of only using intravenous route on survival has to be bigger. But as it could have been foreseen its author is not interested in revisiting a work done 8 years ago because of someone outside of his field of research has some strange ideas. I don’t blame him at all. When I get over this new bout of pessimism I will do the numbers with the same effect size measured on the Vanderbilt study just out of curiosity.

              1. Andrey Pavlov says:

                I expect the effect to be big enough so a small RCT on an Expected Deaths group could be powered at more than 80%.

                And you – nor anyone – have any rational reason to suspect this. Which is precisely what MadisonMD pointed out. And even if it were true, doing preliminary studies as he suggests would further help refine and improve your subsequent studies by establishing a better prior plausibility. Skipping this – whether the effect is there or not, large or not – can only hinder your efforts. In essence it is the Monty Hall problem.

                I would have liked to do the numbers with more information about the Vanderbilt study since I suspect the effect of only using intravenous route on survival has to be bigger.

                You do realize that the only difference between IV and oral administration of any drug is the bioavailability? And that achieving and equivalent serum value will produce equivalent outcomes regardless of route of administration?

                So the only reason to think an IV administration would be beneficial is if there was some barrier to achieving that serum level in the particular patient population in question.

                Once again, you’ve learned how to crunch some numbers and do some stats. You don’t understand how study design works and what it can and cannot tell you. And MadisonMD is more qualified than myself to speak on such matters. You’d do well to listen, rather than argue and think you are the smartest person on the planet.

              2. Windriven says:

                “So the only reason to think an IV administration would be beneficial is if there was some barrier to achieving that serum level in the particular patient population in question.”

                Andrey, the point has been made somewhere in these pages that delivering the desired dosages (megatons per kilogram?) via the oral route is impractical and that IV is the only route that can achieve and maintain the desired serum level. As I recall the pharmacokinetics are such that ascorbate has a short half life though just how short seems to be controversial.

              3. Andrey Pavlov says:

                Andrey, the point has been made somewhere in these pages that delivering the desired dosages (megatons per kilogram?) via the oral route is impractical and that IV is the only route that can achieve and maintain the desired serum level.

                I know. I’m more hammering Andres at the imprecision of his ideas. The issue he should be making a case for is that certain serum levels are not achieved nor achievable, which is independent and completely ancillary to mode of delivery. Basically, I am giving him back a dose of his useless pedantry.

                Of course none of it really matters since it is all just a means to move goalposts anyways. But as you may have noticed I’ve found myself growing a little irate with his prattlings.

              4. MadisonMD says:

                I expect the effect to be big enough so a small RCT on an Expected Deaths group could be powered at more than 80%.

                Highly unlikely unless you select the patients who match the specific mechanism for which the drug operates. Not all SICU patients are the same, and you will get a different population in SICUs at different hospitals depending on the surgery done there. I’m sure the SICU population at Vanderbilt has even changed. You need a hypothesis about mechanism, friend. (Imagine giving imipenem to all ICU patients. It would be much more efficacious if you selected the ones that actually have pneumonia, right?)

                Andres, you place an awful lot of faith on a single non-randomized trial of a drug without mechanism. Imagine how many similar trials went unpublished due to negative results.

              5. MadisonMD says:

                @windriven

                As I recall the pharmacokinetics are such that ascorbate has a short half life though just how short seems to be controversial.

                You link a 2008 review by Riordan posing the question of what is the pharmacokinetics of IV vitamin C in patients with advanced cancer, and proposing it may be longer than for oral Vitamin C. Two studies since that time have addressed this question: here and here.
                The first phase I trial measures halflife of 2+/- 0.6h
                The second phase I trial didn’t quantify halflife, but did plot washout after vitamin C infusion in Fig.1. Halflife looks to be close to 2 h or so.

                So, Windriven, I don’t think short halflife of Vitamin C is in question anymore.

              6. Windriven says:

                @Madison

                Thanks for straightening me out on that. In rereading my original comment, the irony wasn’t as stark as I had intended.

                So… the trial would boil down to replacing the blood volume with Florida’s Natural (TM)? Doesn’t the pulp clog the Jelco?

                But wait … there’s a better alternative! I think I’ve come up with The Next Big Thing in sCAM! OJ colon cleanses. Cures cancer, provides dietary fiber*, and leaves you smelling citrusy fresh. Your car seat will love you for it. ;-) Is it too late to enroll for the next semester at Bastyr?

                * What? You’ve never heard a more outrageous sCAM claim? Read any three random FBA or stanmrak comments.

  19. Kimberley says:

    The vaccine exempt numbers from the kindergarten class may not be as accurate as you think. The local charter school that I am registering my son in won’t accept applications unless all vaccinations that are required for school have been administered. The problem is that my son doesn’t turn five until the summer and the open spots at the school will be long gone by then since open enrollment begins in March. I tried to show the office staff that he had received all the vaccinations he could have received and would be getting another round after his birthday but the whole explanation was apparently beyond them so I signed the Exempt Waiver. Thankfully he got in; enrollment is now closed and he still hasn’t turned 5. In talking with other parents this seems pretty common. I will update his file after he has all the vaccinations but who knows if that form I signed hasn’t already been filed somewhere else. I wonder about the kids (here in California) that are still 4 when they start kindergarten. What a hassle for those parents!

    1. John Snyder says:

      There are no vaccines that must wait until age 5 years. The vaccines typically required for KG are typically given at age 4. I have encountered some instances when parents enrolling their kids before their 4th birthday are given a hard time by misinformed school personnel. That said, this confusion is easily corrected by a note from the provider explaining that the child is up to date.

  20. Sean Duggan says:

    We have a recent case here in Allegheny County in Pittsburgh. The guy hadn’t traveled recently and apparently got his MMR. Good that they’re advertising the places he’s been recently so that they can check to see if others have contracted it. Not so good that they downplay the deadliness of it, stating it only as a problem for the immunocompromised…

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