Over the weekend, some of you might have felt vaguely concerned that the European Medicines Agency is probably going to fast track a swine flu vaccine (meaning skip some preliminary safety testing.) Visit this Harry Potter-sounding organization’s website and read the press release for yourself here. Meanwhile, I was feeling alarmed that National Institute of Health (NIH) money was probably used to fund Raccoon Flu research. This article’s side-splitting section entitled Experimental Infection of Raccoons mentions rectal swabs enough times to make it worth reading. Although, as hilarious and ethically questionable as I found the study’s methods (which include capturing, infecting, and rectally-swabbing raccoons), I suppose I can see the rationale for studying what happens to the flu virus inside an animal that eats out of our trashcans (might I also suggest we test these crafty dumpster divers for recombinant flu strains?) I have a more difficult time understanding how this other flu research article received funding, seeing as the only population to benefit from the study’s findings is alcoholic mice. Hey, I want to study the flu’s effect on my crack-abusing newt. Any takers?
But in all seriousness folks, everyone has been a little nervous about swine flu since the media frenzy surrounding the outbreak in Mexico City in April. After the situation failed to yield piles of corpses, the story faded from the headlines, allowing the WHO to quietly declare the viral outbreak a stage 6 pandemic on June 11th, 2009. I’ve been keeping an eye on the story in anticipation of the southern hemisphere’s flu season followed by our own beginning this fall in October. The most recent WHO update can be found here, with a more comprehensive interpretation of the data here. Essentially, the WHO says we do not yet have a clear epidemiological picture of what’s going on and we should continue to monitor disease patterns as the seasonal flu and the novel H1N1 strain circulate around the globe. Similarly, the CDC reports about 43,771 cases and 302 deaths here in America. If you’re looking to protect yourself, the CDC recommends generically useful strategies like washing your hands and avoiding mouth-to-mouth contact with flu-infected raccoons.
Many of you will be deciding whether or not to get vaccinated this fall. News about fast tracking the flu vaccine triggers media-implanted concern over vaccine safety in many people. I cannot unimplant this concern (beside, concernectomy is not covered by your insurance policy), nor can I really reinstall public trust in certain organizations like the CDC or the NIH that some people now consider part of mainstream American medicine, colluding with big pharma and insurance giants and all that dirty stuff. Luckily for vaccine safety advocates, we don’t have any plans to fast track a vaccine here in the States. Safety reports should be available by the time a swine flu vaccine hits U.S. markets, although critics will rightly point out that the data will not reflect any potential long-term effects. The WHO’s expert advisory group on immunization compiled recommendations regarding H1N1 vaccine, which you can read about here. Just as the WHO recommends that each country consider its vaccine strategy based on its own unique epidemiological profile and resource availability, I recommend that you make the decision to vaccinate based on your own unique risks/benefits analysis.
Of course, it’s unwise to analyze risks and benefits if you don’t really know what they are (unless you’re an elected official.) Since I try to offer people a little something beyond my own general opinion or “informed” speculation whenever possible, I searched PubMed for additional information (beyond CDC, WHO or NIH websites) regarding the safety of routine seasonal flu vaccines, potential pandemic flu vaccines, and the great Guillian-Barre (GB) incident of 1976 in which 25 people died of GB after receiving a vaccine against a strain of novel swine flu. I also searched for information regarding the projected severity of H1N1 pandemic. My search was limited to PubMed, the Internet (including the world wide web at http://www.www.com) and various textbooks I have, which does not cover all the sources out there. Even with my limited search, flu studies are more numerous than “cute kitty” videos on YouTube, so a truly comprehensive review is beyond the scope of this blog. Still, with regards to vaccine safety, I found truckloads of articles discussing traditional inactivated and live-attenuated flu vaccine safety. I’ve pared the list way, way down to a few of the most crucial articles for review in this blog entry, but I read the others and will go ahead and disclose that they have influenced my opinion. I am always happy to provide references to anyone who is curious where I’m getting my information. For people looking for some down-and-dirty vaccine drama, I’m sorry to say that I could not find any reputable articles providing evidence that traditional flu vaccines are not safe, though I will address the Guillian-Barre link. (If you have in your paws a damning piece of flu vaccine evidence, please send it my way.) And I could not find any concrete answers regarding the projected severity of the H1N1 pandemic beyond “honestly, we don’t know.” I did, however, find an excellent expert review that is easy to comprehend for non-medical folks. The following discussion will contain some jargon, which you can easily understand after brushing up on virology 101. For those of you who want a brief review here, the next paragraph contains all the vocab you really need to know, and following the links will help you learn a bit more about genetics, microbiology and immunology as well! For readers well-versed in the sciences, skip the next paragraph.
A virus is an infectious agent composed of a nucleic acid core (like DNA or RNA, which is the virus’s genetic information) and a protein coat. The virus may also come with a few pre-packaged enzymes, which help the virus enter and exit the cell, undress inside the cell, and high-jack the cell’s genetic and metabolic machinery for the purposes of replication and proliferation. These enzymes are sometimes the targets of enzyme-inhibiting antiviral medications. (Parenthetically, viruses do what they do because they do not have their own organelles or cellular components necessary for metabolism and replication. Since the biological definition of life encompasses metabolism and replication, viruses are not alive–much like these people.) The proteins on the outside of the viral coat are called antigens. For example, the name H1N1 refers to the specific antigens on the outside of the influenza A viral particle, hemagglutinin and neuraminidase. Neuraminidase is also an enzyme (all enzyme names end in the suffix “-ase”.) These antigens are usually the targets of vaccination. A vaccine will (hopefully) help your immune system to recognize these antigens and launch an immue reponse against the virus.
When attempting to predict how safe a new vaccine will be, it might help to look at other vaccines of its kind that have come before it. The rationale here is that the new pandemic H1N1 vaccine will probably be made exactly like the others, only with an antigenic component unique to H1N1 inserted into the standard vaccine cocktail. This rationale, unfortunately, is an oversimplification, as development of an H5N1 avian flu vaccine illustrates. For example, vaccine production is switching from egg-based to cell-based methods (Ca-Ching!!$$$$.) Additionally, as Hovden, Cox and Haaheim (2007) reiterate in their excellent review of flu vaccination in people with COPD, current flu vaccines usually do not contain an adjuvant, whereas a vaccine against a novel flu strain may need an adjuvant to make it effective in an immunologically-naive population.
With these caveats in mind, the safety record of current seasonal flu vaccines is well established. Our friends Hovden et al. (2007) will vouch for this claim. These people probably wouldn’t (although check out their awesome professional credentials). Although some of the information on nvic.org is not entirely misleading (I can’t find a link to provide a warrant for that claim. I tried), I think that the article by Vellozzi et al. (2009) published in this month’s Vaccine journal is a bit more illuminating, seeing as it uses 15 years of data from the VAERS to track the safety of trivalent inactivated flu vaccines (TIV). Though there are some limitations with the study (mostly limitations inherent to the nature of the VAERS, which is a passive surveillance system subject to biased reporting and underreporting), the authors did look at a time period between 1990 and 2005, in which an estimated 747 million doses of TIV were administered. During this time, the VAERS received just over 18,000 reports of TIV-related adverse events, 14% (about 2500) of which were serious. That’s about a 0.0000033% chance of a serious adverse event related to a TIV flu vaccine, and a 0.0000244% chance of any adverse event. Guillian-Barre was reported at a rate of 0.78 per million vaccines. The study did not find any changes in overall vaccine safety between 1990 and 2005. The findings can’t be generalized in children under 18 years old or vaccines grown in anything other than egg. You can read about the safety of TIV in children and adults with asthma here and safety of H5N1 vaccine here plus here and live attenuated vaccine in adults here and TIV vs. live attenuated nasal spray vaccine in children here. Just to name a few.
On the subject of the 1976 swine flu that failed to amount one of those super-sexy killer pandemics but did generate a panic vaccine that killed 25 people by causing Guillian-Barre (GB): an in-depth analysis published in the Journal of Infectious Diseases by Evans, Cauchemez, and Hayden (2009) notes that around 45 million people received this vaccine over a 10-week period in 1976, with a risk of GB between 4.7 and 11.7 cases per million vaccines. That amounts to a 0.0000117% risk of getting GB from the vaccine and a 0.0000005% chance of dying from it (I’d like to credit my calculator with these numbers.) The study also provides an excellent breakdown in Table 3 of the number of study participants that would be needed to detect rare adverse events–you can see why clinical trails have difficulty in this area. If you’re a statistics nut, read this sucker. My point here is not that those 25 deaths were insignificant, but that these risks weighed against the possible risks of a severe flu pandemic warrant consideration. Even if the new flu vaccine is as “unsafe” as the 1976 disaster vaccine, it might still be worth the risk. Plus, we’re a little better at treating GB now.
So what are the chances that pandemic H1N1 will be a bust like it was in 1976? Be suspicious of anyone who assuredly, confidently answers this question with anything other than an “I don’t know.” The best review I found was published in Virology Journal and written by a dude named William R Gallaher, retired professor emeritus from LSU, holder of a U.S. patent for an Ebola antiviral strategy, and all-around nice guy. His review is comprehensive and easy to read. He concludes that, although the future course of the outbreak can’t be predicted, the current pandemic H1N1 strain has significant pandemic potential and warrants rapid development and possibly worldwide administration of a new vaccine. He’s also generously offered to be the new vaccine’s first test subject. His conclusions come from analysis of antigenic drift in both of the viral surface proteins. If we are going to trust CDC numbers, you have around a 0.0069% chance of death from this current pandemic H1N1 strain, although I won’t even attempt to calculate your chances of actually contracting the virus.
Like Gallaher, I’ll be getting a flu vaccine this fall. I’ll get a flu vaccine because I’m a health care worker and I would not want to transmit flu to any of my patients. However, I won’t let them poke me unless there’s been at least some preliminary safety testing. I mean, what if some sort of new adjuvant causes one to write overly verbose blog entries??? I certainly wouldn’t want that.
I hope this review has been educational in terms of H1N1 vaccination and flu information in general.
Evans, D., Cauchemez, S., and Hayden, F. G. (2009). “Prepandemic” immunization for novel influenza viruses, “swine flu” vaccine, guillian-barre syndrome, and the detection of rare severe adverse events. The Journal of Infectious Diseases, 200, 321-328.
Gallaher, W. R. (2009). Towards a sane and rational approach to management of influenza H1N1 2009. Virology Journal, 6(51). 7 pages.
Hovden, A. O., Cox, R. J., and Haaheim, L. R. (2007). Influenza: the virus and prophylaxis with inactivated influenza vaccine in “at risk” groups, including COPD patients. International Journal of COPD, 2(3), 229-240.
Vellozzi, C., Burwen, D., Dobardzic, A., Ball, R., Walton, K., and Haber, P. (2009). Safety of inactivated trivalent influenza vaccine in adults: background for pandemic influenza vaccine safety monitoring. Vaccine, 27, 2114-2120.