Vaccine refusal: it ain’t nothing new

imgres-1I’ve been fascinated by vaccine refusal for a long time, but for whatever reason I had never thought much about its history–at least not stretching back more than a few decades.

Perhaps it shouldn’t be surprising, but turns out that powerful anti-vaccine sentiment has been around for a long time! I just finished Pox: An American History by Michael Willrich, which explores the anti-smallpox vaccine movement during the last major epidemic in the US. Around the year 1900, smallpox emerged from the American South, where it had been festering, and started rampaging across the country, sparking epidemics in major cities like New York and Boston.

Desperate public health officials imposed mandatory vaccine drives. When people didn’t want to be vaccinated–and a lot didn’t–they risked being fined, thrown in jail, or physically restrained while somebody gave them the vaccination. Of course, vaccination laws were applied very differently depending on whether someone was wealthy or poor. In New York’s tenements, brute squads literally chased down and vaccinated every person they could find, breaking down doors and tearing children out of the arms of their mothers. The same was not true on Park Avenue.

All kinds of people joined anti-vaccine societies around the country. Celebrities weighed in too, although at that time people like Mark Twain and Williams James were voicing anti-vaccine sentiments. A little different from today, when anti-vaccine stars tend to be people like Jenny McCarthy and  Jim Carrey. It’s also striking how little the reasons for vaccine refusal have changed in 100+ years. Parents then were primarily concerned about their children’s safety. They cited all sorts of cases in which vaccines had been followed by death or terrible illness. Many believed that it was better to risk smallpox (especially in its milder variola minor form) than to receive the vaccine.

Of course then they had a point. People had very real reasons to worry about vaccine safety. Although local governments could compel people to be vaccinated, they could not guarantee the safety of the vaccines being administered. In the early days, when people were vaccinated with material from the lesions of another vaccinated person, the risk of some unwanted pathogen being transmitted alongside the vaccine virus was significant. In a particularly awful example from 19th century Italy, 63 children were vaccinated with infectious material taken from an infant who appeared to be healthy. Forty-four of those kids developed syphilis. Some also infected their mothers and nurses. And keep in mind this was before we had antibiotics–when syphilis often proved a death sentence.

Later, cows were used to produce the smallpox vaccine, which really helped ramp up production. It also meant that anyone with a cow and access to some virus could join the vaccine business–small, filthy operations were literally operating out of backyards in places like Brooklyn. There simply was no quality control or regulation.

Not surprisingly, vaccines at that time were often horribly contaminated. The vaccine site often became infected. A man or woman might lose days or weeks of work due to their inability to use the vaccinated arm–and the family that depended on them would suffer. That was sort of a best-case scenario, though. A number of children died of tetanus or other infections after vaccination. You can imagine how that stoked fear of the vaccine! It also horrified many of the doctors who unwittingly administered tainted vaccines and saw their patients suffer the results. Eventually, the attention these cases drew to the lack of quality control in vaccine production would revolutionize the way vaccines were produced, and quality control would become one of the industry’s major concerns. The government would also eventually recognize that it had a responsibility to regulate vaccine production and care for people harmed by vaccines.

The book also draws attention to a major divide in the medical community that was emerging at the time. Homeopaths and other alternative medicine practitioners were very active in the anti-vaccine movement. At the same time, allopaths were coming out strong in favor of vaccination and consolidating their hold over the medical profession. This is another source of tension that seems to have changed very little during the last century.

Willrich gives a sympathetic portrayal of the very real conflicts posed by mandatory vaccination as he follows the outcomes of court cases challenging mandatory vaccination laws. What are the rights of the individual weighed against the many? Especially when the risk of bodily harm to the individual is real? It’s interesting that a lot of passionate vaccine critics then were also active in the women’s rights and civil rights movements of the day. He makes a good case that society’s struggles with vaccine refusal have helped shape our understanding of civil rights. It’s a fascinating book, definitely worth a read!

A side effect of the flu vaccine teaches us something new about narcolepsy

images-3You’ve heard of narcolepsy. Probably the most famous symptom is someone falling asleep during the course of normal, daytime activities (like conversations). It’s a neurological disorder in which the brain is unable to properly regulate sleep-wake cycles. Experiencing sudden muscle weakness when you feel strong emotions is another symptom, as is sleep paralysis (when you wake up but cannot move or talk). Reading these symptoms makes me wonder if I have it! But it’s rare–it has been estimated to affect about 2 out of every 10,000 people.

We don’t have a great handle on what causes narcolepsy. Over the past few decades, evidence has started mounting in favor of a new hypothesis: that narcolepsy is an autoimmune disease. It became clear that the disease is  associated with a certain HLA genotype, DQBq*0602 positive (the human leukocyte antigen or HLA genes are involved in immunity). About 30% of the general population carries this genotype, but it’s found in 99% of narcolepsy cases, implicating the immune system. In addition, when researchers injected antibodies from narcoleptic humans into mice, the mice developed narcolepsy-like symptoms.

Now we’ve got a new source of evidence supporting the autoimmune hypothesis: a link between a flu vaccine used in 2009 and a scattering of childhood narcolepsy cases. As you may remember, 2009 was the year of the big H191 flu scare. In Europe, some countries used a vaccine called Pandemrix that was produced by GlaxoSmithKline. Researchers in Scandinavia were the first to discover that getting the flu shot was a risk factor for developing narcolepsy. In western Sweden, the odds of developing narcolepsy were roughly 25x greater for kids that got the Pandemrix shot than those who did not; in Finland, they were 13x greater; and in England, they were about 16x greater. Eventually, similar results were found in children who had received the vaccine in France too. Here, you can see a graph depicting the spike in cases following the 2009 vaccination campaign in Finland. Pretty striking!

journal.pone.0033723.g001

Spike in childhood narcolepsy cases in Finland following H1N1 vaccination. From: Partinen M, Saarenpää-Heikkilä O, Ilveskoski I, Hublin C, Linna M, et al. (2012) Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland. PLoS ONE 7(3): e33723. doi:10.1371/journal.pone.0033723

Now this is scary stuff, but I’d  like to point out that narcolepsy is actually a rare side effect of the shot. Only 1 of every 16,000 vaccinated children developed narcolepsy. And it’s important to remember the H1N flu itself can be pretty nasty, which is why the vaccine was developed in the first place. In Sweden, for example, even with the vaccination campaign there were 4,753 cases of H1N1 flu in children: 571 needed hospital care, 27 needed intensive care, and 4 died. So death occurs in about 1 of 500 kids who get the flu ,and narcolepsy occurs in about 1 of 16,000 kids who get vaccinated with this particular shot. Balancing the risk associated with the shot and the risk associated with the flu is tough–but for my kids, I would still favor the odds on the shot. Nevertheless, by 2011 the WHO had restricted the use of Pandemrix in children. This makes sense since other types of flu shots — that have not been linked to narcolepsy — are available.

Because narcolepsy seemed to be a side effect primarily of the European vaccine, attention centered on an ingredient found only in Pandemrix. This vaccine contained an adjuvant called ASO3 (an adjuvant is a material that helps create a strong immune response), whereas US versions did not. Thus, scientists hypothesized that it could be the strength of the immune response, which is greater when an adjuvant is involved, that leads to increased narcolepsy risk.

Now here is where things get tricky. It seems pretty clear at this point that in rare cases, the Pandemrix H1N1 vaccine triggers narcolepsy. But it looks as though the flu itself can trigger narcolepsy too. Getting the H1N1 flu, in particular, seems to be an important risk factor. Researchers at the People’s Hospital of Beijing University compared the number of new narcolepsy cases diagnosed every year from 1998–2012. They found a huge spike in new cases in 2010, following the H1N1 winter flu epidemic there. In 2010, 201 new cases were identified–more than the 187 new cases identified in all of 1998–2009 combined! By 2011 and 2012 the number of cases were back down to normal. So it looks like both the vaccine AND the flu can lead to narcolepsy. Doesn’t this remind you of the post I wrote about the flu vaccine and Guillain-Barré syndrome a few weeks ago?

The kind of risk associated with flu is not entirely clear yet, however, as H1N1 infection doesn’t seem to have contributed to the narcolepsy spike in Finland or in some other countries. Perhaps infection was more intense in China, in terms of both the numbers of infected people and the strength of the immune response. It’s not clear yet, but it will be interesting to see what we learn as time goes by.

So why would the flu vaccine/flu cause narcolepsy? In a recent article in Science Translational Medicine, researchers found that patients with narcolepsy have immune cells primed to attack a hormone called hypocretin. The brains of people with narcolepsy are missing the neurons that produce hypocretin, so this makes sense. Their immune system appears to have killed them off. And here’s where it all comes together: part of the H1N1 hemagglutinin protein closely resembles the parts of hypocretin visible to immune cells. In the laboratory, exposing immune cells from narcolepsy patients to these viral fragments increases the frequency of hypocretin-reactive cells! This is no good for the cells that produce hypocretin and suddenly become attractive targets for the immune system.

Who is most at risk for developing narcolepsy after the shot? All post-vaccine cases identified by three big narcolepsy centers in France, Canada, and the US have had a specific HLA genotype: DQBq*0602 positive. That was the genotype I mentioned before, the one that 99% of narcoleptics have. The post-vaccination cases identified in Sweden also had this genotype. So it seems as though the shot isn’t causing narcolepsy in just anyone. Instead, Pandemrix seems to be a precipitating factor for children who are already susceptible to developing the disease. Therefore, researchers have proposed HLA typing individuals prior to administering flu vaccines like Pandemrix.

Researchers have also called for additional studies examining whether non-adjuvant flu vaccines increase the risk of narcolepsy. The H191 vaccination campaign was unusual in that it involved the mass vaccination of tons of kids in a short period of time, facilitating our ability to recognize side-effects, like narcolepsy, linked with the shot. It’s also notable, but not surprising, that the narcolepsy connection was discovered in Scandinavia, where over 75% of kids were immunized and the health reporting is of excellent quality. It’s still possible that other flu vaccines carry a risk, probably less pronounced, that is hard to detect under normal conditions (like the relative chaos that is the US healthcare system). I think we are going to see some interesting research emerge in this area!

Does the flu vaccine cause Guillain-Barré syndrome or not?

urlGuillain-Barré syndrome (GBS) is a pretty scary condition. It starts with weakness and tingling in the extremities and can eventually leading to paralysis. Although most people recover in time, death can occur. Luckily, it’s a rare disease. It’s thought to result from an autoimmune process in which peripheral nerves are demyelinated and destroyed.

What causes GBS? Infections seem to be a major trigger. In about two-thirds of cases, the syndrome is preceded by either a gastrointestinal or respiratory infection. Campylobacter enteritis seems to be the most common trigger, but influenza, cytomegalovirus, Epstein-Barr virus, and HIV have all been implicated too. It appears that, in rare cases, these pathogens trigger the autoimmune cascade that leads to the diseases.

The 1976 H1N1 vaccine and GBS

Way back in 1976, researchers noticed something scary. 1976 was the year of the big swine flu epidemic scare. In February of that year, two army recruits at Fort Dix, in New Jersey, tested positive for swine flu. Researchers believed the strain they were infected with was similar to the one that had caused the 1918 flu pandemic that had killed millions. When they looked a little harder, they found that hundreds of other recruits at the base had been infected as well. Because these were not folks that had contact with pigs, it meant that the virus was spreading from person to person. Naturally, people were nervous. The government decided it would produce a vaccine against this strain and vaccinate as many people as possible, in order to head off what it feared might be a terrible pandemic.

Something strange happened though. Cases of GBS in people who had received the flu vaccine started cropping up. Hundreds of them. In 2009, The New York Times ran the story of Janet Kinny, a woman who developed GBS after receiving the shot in 1976. GBS put this young mother in the hospital for a month, paralyzed from the neck down. She recovered, but not everyone was so lucky. More than 30 of the people who developed GBS after getting a flu shot that year died. Epidemiologists spent a while debating whether or not this cluster was just a coincidence. In the end, most agreed that the shot really was associated with an increased risk of GBS. Researcher Lawrence Schonberger estimated that people who received the 1976 flu shot were roughly 7 times more likely to develop GBS than people who did not. For every 100,000 people vaccinated, approximately one got GBS. In December 1976, after having immunized more than 40 million people and failing to see evidence that the H1N1 pandemic was actually going to materialize, government officials called off the vaccination campaign due to the GBS risk.

Not surprisingly, people became wary of flu vaccines. Nobody wants to get GBS. A lot of work has been done over the years to try to clarify the risk that flu shots pose, but GBS is such a rare condition that it has been hard to put together studies large enough to shed light on this problem. Well, this year, three important studies on the flu vaccine and GBS came out. These were huge studies that each looked at millions of people, and they’ve provided a lot of insight into the relationship between vaccines and GBS.

2013: The year of gigantic flu shot/GBS studies

The first study appeared in Clinical Infectious Diseases. The authors mined data collected over 13 years (from 1994–2006) by Kaiser Permanente. Those of you from the West Coast know that Kaiser Permanente is a big insurer/hospital system with tons of clients. Using records for 3 million of patients, they were able to identify 415 confirmed cases of GBS. Sure enough, exactly two-thirds of these patients had suffered a respiratory and/or gastrointestinal illness in the 90 days preceding the onset of their GBS. But only 25 had received a vaccine of any kind in the 6 weeks prior to onset. In this study, GBS was NOT associated with getting a prior flu shot. However, the authors pointed out they could not rule out a very small increased risk of GBS; it’s always possible that with a larger sample size (i.e. more cases) they would have increased power to identify a small association.

Another even larger study appeared in the Lancet Infectious Diseases, and it, too, focused on seasonal flu vaccines. Carried out using the universal health care system records in Ontario, Canada, it was able to identify 2,831 incidents of GBS between the years of 1993 and 2011. The authors of this study found that the risk of developing GBS was roughly 50% higher in the six weeks following a seasonal flu shot, vs the risk experienced 9–42 weeks after. Thus, there really did seem to be a small, increased risk of GBS associated with seasonal flu shots. However, the authors found that actually GETTING the flu was a much bigger risk factor for GBS. In the six weeks after seeking medical help for the flu, the risk of GBS was roughly 16 times greater (vs 1.5 times for the shot) than in the weeks following the danger period. To put these findings in context: For every million people vaccinated with the flu shot, about 1 would get GBS, and for every million people who got the flu, 17 would get GBS.

The third study appeared in The Lancet, and it focused on the flu vaccine in one special year: 2009. You may remember that 2009 was the year of another H1N1 swine flu scare (and thus another H1N1 swine flu vaccine). So if any flu shot was linked to a greater risk of GBS, as in 1976, it seems like it would be this one. When focusing on this single year, researchers found an increase in GBS cases associated with the vaccine. Of the 23 million people who received the H1N1 vaccine and were included in the study, 54 developed GBS within 6 weeks of the shot. This works out to be about 1.6 extra GBS cases for every million people vaccinated. Thus, there WAS a slightly higher risk of GBS linked to the shot–but it was tiny. So tiny, the authors point out, that most studies of seasonal flu vaccines simply wouldn’t be large enough to detect the association. The sample size issue may well explain why the first study (based on the Kaiser Permanente data) did not identify an association between flu vaccines and GBS.

The take-home message: the extremely low risk of vaccine-related GBS is outweighed by the much higher risk of flu complications

So it appears that there is a small risk of GBS associated with flu vaccines. But, as flu researchers have been quick to point out, the risk associated with actually GETTING the flu is much higher. Poland and colleagues have posed a thought experiment in the Lancet on this subject. They point out that if everyone in the US had gotten the 2009 H1N1 vaccine, it’s estimated that 22 vaccine-related deaths would have occurred. But it everyone had gotten the H1N1 flu, 12,470 deaths would have occurred. Although the side-effects of a vaccine loom large in our minds, it’s important to put these risks in perspective: most vaccines prevent dangerous diseases, so foregoing a vaccine poses its own (often much greater) risks.

These modern studies still don’t explain exactly what happened in 1976. Why did that particular vaccine cause the syndrome at such a high rate (1 per 100,000 vs. 1 per 1,000,000 for modern vaccines)? Nobody knows. One explanation for the increased GBS risk is that the vaccine was contaminated with a bacterial trigger like Campylobacter.  Another explanation, which seems more plausible, is that something in the vaccine resembled nerve cells–so that when a recipient’s body mounted an attack against the vaccine, the attack might have hurt nerve cells as well. It would be comforting if, eventually, we could identify the problem.

Does the polio vaccine cause polio?

imgres-2One claim that I’ve heard a lot from vaccine opponents is that the polio vaccine is actually causing polio epidemics instead of preventing them. Scary, right? On websites like “GreenMedInfo” you see headlines like Polio vaccines now the #1 cause of polio paralysis. And Joseph Mercola maintains that because of problems like this, “the polio vaccine is not the ultimate solution to prevent” polio.

Is any of this true? As it turns out, there IS a grain of truth to this claim. But the truth is way more complicated than vaccine skeptics seem to understand, and, as it happens, the solution is more vaccination, not less.

Here’s the deal. There are two types of polio vaccine, one that involves the injection of dead virus and another that involves oral drops filled with live (but non-disease causing) virus. Here in the U.S., we use the first type of vaccine. But there are many benefits associated with the second type of vaccine: it’s easier to administer (drops vs shots), it provides stronger protection, and here’s the biggie: because it can spread after being administered, it effectively inoculates other people in the community. This is called passive immunization, and it’s definitely a good thing! It means the protection of the vaccine extends beyond just the people who get vaccinated. The virus can remain in a child’s feces for up to six weeks, during which time she has the potential to inoculate the people around her.

There is a dark side to this passive immunization, though. Give the vaccine-derived virus enough time to spread, and it can begin to mutate. Tick tick tick. Enough mutations, and it may regain its ability to paralyze. When does this happen? When the proportion of vaccinated kids is low. Surrounded by plenty of susceptible kids, the likelihood that a vaccine-derived virus can circulate for long enough to gain these mutations goes way up.

Unfortunately, this situation sometimes occurs. There have been a number of vaccine-derived outbreaks of polio. In total, scientists think that, since the year 2000, there have been 20 outbreaks of vaccine-derived polio in 20 countries, resulting in 655 vaccine-derived polio cases. The biggest outbreak, involving hundreds of kids, happened in Nigeria. This isn’t surprising, because vaccination stopped in some regions of the country for over a year in the early 2000s.

The counterintuitive solution to fighting vaccine-derived outbreaks is to increase vaccination rates. That way, children are inoculated with the harmless version of the virus and can’t be infected with any “bad” versions floating around. Vaccine-derived strains are nipped in the bud before they have time to accumulate dangerous mutations.

One thing to ask people critical of the polio vaccine because of vaccine-derived outbreaks is what they recommend as a substitute. Joseph Mercola’s big idea is to cut down on sugar, apparently. Sadly, sugar consumption isn’t a big problem in most of the places where polio is still a problem. So I think we can rule that solution out. Sayer Ji, founder of GreenMedInfo, recommends improved sanitation. While improved sanitation certainly cuts down on opportunities for infection (polio is spread through the fecal/oral route), it can paradoxically create more opportunities for paralysis. Why? The older you are when you become infected with polio (and the age of infection goes up when opportunities for infection go down), the greater the odds of paralysis. So I think we can rule that solution out too (although improved sanitation has many other benefits, and it is definitely a worthwhile goal).

So while vaccine-derived polio outbreaks are a real thing, they are not a reason to abandon the polio eradication campaign, which has reduced the number of new polio cases by 99% since it began in the late 1980s.

The bogus HPV vaccine article that just won’t die

vaccinationI came across this article on Facebook today: Lead Developer of HPV Vaccines Comes Clean, Warns Parents & Young Girls It’s All A Giant Scam. It was published on some entertainment website called feelguide.com back in July, but it just won’t die. It’s got 198,000 Facebook likes, and it’s been tweeted 631 times. It claims that Diane Harper, a scientist involved in the clinical trials for Gardasil, one of the HPV vaccines, did a 180 and decided that the vaccine is no good. According to the article, she announced this abrupt change of face at the 4th International “Converence” on Vaccination in Reston, Virginia. She came clean to the audience so she “could sleep at night.”

The article conveniently makes it very difficult to distinguish between the (supposed) paraphrasing of what Harper actually said at that meeting and the interpolations of other people. It says scary things like “44 girls are officially known to have died from [HPV] vaccines.” Uh, really? Wouldn’t that death toll be all over the newspapers? Well, maybe not, since it’s not at all true.

You might wonder how this website can get away with printing things that are demonstrably false. Yesterday somebody pointed out to me the feelguide.com website’s disclaimer: “Feelguide.com contains published articles, speculation, assumptions, opinions as well as factual information. Information on this site may or may not be true and is not meant to be taken as fact.” And the author? Is he a vaccine expert? Nope, his name is Brent Lambert. As it happens, he is also Editor-In-Chief of this fabulous website, and you can reach him at his gmail address. Super professional.

Where did this article come from, you ask? Almost word for word, it was taken from an article that appeared on the website LifeWise in June. This article, in turn, seems to have drawn on a 2009 article in the Sunday Express by Lucy Johnston. (Note: The Sunday Express may sound respectable, but it’s actually a British tabloid.)  Their claims that Diane Harper said all this stuff were debunked back in 2009, the very week that they came out. Ben Goldacre of the Guardian talked to Diane Harper himself. In Harper’s words:

“I did not say that Cervarix was as deadly as cervical cancer. I did not say that Cervarix could be riskier or more deadly than cervical cancer. I did not say that Cervarix was controversial, I stated that Cervarix is not a ‘controversial drug’. I did not ‘hit out’ – I was contacted by the press for facts. And this was not an exclusive interview.”

The original article was promptly taken off the Sunday Express website, and Harper complained to the Press Complaints Commission.

How did this whole brouhaha start? For whatever reason, Harper decided to speak at the 4th International Public Conference on Vaccination, held by the National Vaccine Information Center in Reston Virginia. Sounds bland enough, right? But as it happens, the NVIC is one of the largest, most vocal anti-vaccine groups out there. Why would she attend such an event? I guess it’s possible that she was tricked, that she didn’t realize what she was getting into. Working in the vaccine field, it seems she would have to be familiar with the NVIC, though. Maybe she was trying to engage vaccine critics, hoping that a little education would bring them around. Perhaps we’ll never know. But not surprisingly, it appears that attendees twisted her words in the press.

So how did all the same 2009 tabloid junk get recycled in a 2013 article? And why do people take it at face value? Lord only knows.

I frequently see people post articles like this in places like Facebook after adding something like, “C’mon, people. Do your research. Vaccines are dangerous.” I am all for people doing research about vaccines. There is so much great vaccine research available that if most vaccine skeptics really delved into it, I think they would rapidly change their minds. But does anyone really consider reading an article like this research? Even if the lack of any citations didn’t clue you in, and you didn’t know about the backstory for this chunk of lies, wouldn’t the misspelled words, the disclaimer that says the website contains  information that “may or may not be true,” and the Editor-in-Chief’s gmail address give you reason to pause? Is this really where you want to get the information you use to make medical decisions? Feelguide.com? C’mon people. Do your research. For real.

If you’re interested, more information about this particular zombie anti-vaccine meme can be found on the Respectful Insolence and Skeptical Raptor blogs.