Anthrax - Not Just a Thrash Metal Band

The other day, I got into a bit of a back-and-forth on Twitter with some folks that question vaccines. I know, I know. Big surprise! One of those people was comedian Rob Schneider, who has recently come out as a vocal critic of California bill AB 2109, which would require parents to get informed about vaccines before they could get a personal belief exemption. Schneider chimed in with a rather bone-headed comment to me:

Or, "I probably didn't think things through, but I'm going to ask anyway."

This isn't a comment that really surprised me or threw me for a loop. I mean, I wrote about it back in November 2010 and reposted the article a little over a year later, since I noticed the argument being brought up yet again. Schneider's comment really just illustrates that he either has not really thought the question through, doesn't understand the subject, cares little to none for people around him or some combination of the above. Suffice it to say, there are very good reasons to be concerned about those who do not vaccinate.

But that's not what this post is about. Rather, it's in answer to a question asked by another person who, presumably, follows Mr. Schneider and saw my exchange with him. This person simply wondered what I thought about complications from the anthrax vaccine. This caught me off guard. I suspected there was probably a bit more behind what appeared to be a very simple question. And sure enough, there was. It wasn't just complications in general, but specifically a possible connection between the vaccine and autoimmune disorders, fatigue and hypersomnia. I had to admit that I didn't know much about anthrax vaccine, but I promised I'd look into it.

And so, here we find ourselves.

I decided to turn my response into a blog post for several reasons. 1) The answer is a bit too complicated for a 140-character tweet. 2) As I started to look into it more, I got rather intrigued. 3) I like sharing knowledge. This is probably a good time to remind readers that nothing you read here should be taken as medical advice; I'm not a physician, so if you're looking for medical advice, see your doctor. I also have limited resources both in terms of time and access to journals. I limited my research for this post to articles published in the medical literature and available on PubMed. There may be some other studies out there that reach different conclusions that me, and I'm definitely open to additional evidence, as long as it is sound. Finally, before I get to actually answering the question I was asked, I think a bit of background is in store. If you'd rather ignore the details, scroll on down to the bottom. If not, sit back, relax and put your learning cap on.

The Disease

Anthrax is a pretty nasty little bacterium. Caused by Bacillus anthracis, it can cause three different types of infection: cutaneous (skin) infection, gastrointestinal infection and inhalation infection. Cutaneous is the most common and mildest form. It can be treated with antibiotics, but if left untreated, it is fatal in about 20% of cases. Gastrointestinal infection can also be treated with antibiotics, but has a much higher fatality rate if untreated, rating anywhere from 25%-75% mortality. Inhalation infections are the most dangerous, with an untreated fatality rate of 80% or higher. In this latter form, even treatment with antibiotics is no guarantee of survival, with death rates hovering around 45%. Of course, as with all infectious diseases, there are other problems associated with infection besides death: cutaneous infections produce sores with some tissue death, possibly accompanied by swelling or fluid build-up; GI infections may involve nausea, vomiting, diarrhea and anorexia; and inhalation infections cause severe difficulty with breathing.

Thankfully, in the U.S., anthrax is not particularly common. The most likely routes of exposure are handling infected animal products (usually imported from regions in which anthrax is common), inhaling spores from contaminated animal products or eating undercooked meat from an infected animal. And then there's weaponized anthrax, something that is fairly easily accomplished thanks to how stable the bacterial spores are. I wasn't able to find anything suggesting that it could be transmitted from one person to another, so that route of exposure it likely out. In short, unless you work in a setting where exposure is likely (e.g., tanner, lab personnel working with anthrax, military, etc.), your risk for this disease is probably very, very low.

What About the Vaccine?

There is only one licensed anthrax vaccine in the United States, Anthrax Vaccine Adsorbed (AVA), which was first approved in 1970 (PDF). Approval of the vaccine was based on a placebo-controlled study in mill workers (PDF) and a couple studies conducted by the CDC. It is around 92% effective at preventing infection, regardless of the route of exposure. Approved only for adults aged 18-65, it is administered as a three-dose initial series, followed by two boosters at 12 and 18 months, with additional boosters every year to maintain protection.

Anthrax vaccine is not on the recommended schedule for children or adults, but on December 15, 1997, amid growing concerns about the possible use of anthrax as a biological weapon, the U.S. Department of Defense (DoD) announced that all military personnel would be vaccinated against the disease. This program resulted in over 1.6 million doses being administered to about 426,000 service members as of April 12, 2000.

We already know that with just a recommended vaccination schedule, there will be people with reservations, shall we say, about getting any of the vaccines. When the vaccines become truly mandatory (i.e., "get vaccinated or else"), concerns about safety seem to ramp up a bit more. Despite the potential for administrative or disciplinary actions, some service members refused the anthrax vaccine. These concerns were, understandably, taken seriously by the DoD. Think about things from their perspective for a moment: you face the threat of a biological weapon that could, at the very least, put a large part of your force out of commission, if not outright kill a majority; the vaccine that prevents that threat is being refused because of safety concerns; if the safety issues reported are real, then the vaccine could, itself, be a threat to your forces and, thus, the safety of the U.S. It wouldn't be in the best interests of the military if the vaccine were putting their soldiers out of action for any significant length of time or causing chronic illnesses that could interfere with the performance of their duties.

So What About Those Safety Questions?

In response to the concerns raised by military personnel, the DoD conducted several surveys of service members and examined the Vaccine Adverse Events Reporting System (VAERS) over the period 1998-2000. They found that adverse reactions were generally limited to local reactions that were of short duration. There was no pattern of unexpected severe events, suggesting that there was no causal connection between the vaccine and these reports. However, the surveys and VAERS study did have some limits: they had small sample sizes, meaning rare events may go undetected; a retrospective approach could introduce recall bias; and the studies weren't designed to detect chronic, long-term adverse events.

In 2002, at the request of the Department of Defense, a civilian panel of physicians and scientists reviewed VAERS data to assess the safety of the vaccine. Like the DoD's review, the Anthrax Vaccine Expert Committee did not find a consistent, unusual pattern or high frequency of serious adverse events connected with the vaccine. Even though roughly three-quarters of the reported events dealt with systemic effects like malaise, headache, etc., only 6 of the 602 reports were judged as possibly or probably due to the vaccine.

The same panel of experts performed an expanded review of AEs reported to VAERS in 2004. Of 1,841 reports, 147 described a serious adverse event, but of those, only 26 were rated as having a tentative connection to the vaccine. Of those, most were, again, local to the injection site. As with the earlier study, the researchers concluded that there was "no evidence for an unusual rate of any SAE or OMIAE [other medically important adverse event] attributable to AVA."

Not content to look only at VAERS data, in 2006 the DoD also examined hospitalization rates (PDF) for service members. The study was quite large (170,723 service members) who were deployed between 1998 and 2001. Looking at 14 different hospitalization categories, as well as any-cause hospitalizations, the study found fewer hospitalizations for any-cause, as well as some respiratory and blood-borne illnesses, post-vaccination compared to pre-vaccination. The remaining categories showed no significant differences between pre- and post-vaccination. The authors added that:

Additionally, we found no evidence of an association between anthrax vaccination and hospitalization due to a number of specific disease outcomes, such as autoimmune diseases, asthma, amyotrophic lateral sclerosis, systemic lupus erythematosus, or fibromyalgia.

Researchers at Boston University School of Public Health took a slightly different approach. Since all military personnel undergo physical exams, the researchers compared physical exams and lab analyses of immunized and unimmunized aircrew members. The found "[n]o association between anthrax immunization and a clinically relevant change in a tested physiologic parameter".

Not to be left out, the Food and Drug Administration also took a peek at VAERS reports from 1998 to 2007, during which period over 6 million doses of the vaccine had been administered, with just 4,753 adverse events reported to VAERS. They found no distinctive pattern indicating a causal connection between the anthrax vaccine and serious reported events. As with all vaccines, however, they stressed the importance of continued surveillance to try to detect possible rare, serious events.

Despite all of this information confirming the safety of the vaccine, concerns still persist. And, interestingly, an explicit informed consent procedure (as opposed to an implied consent with all other required vaccinations for the military) could serve to heighten concerns, rather than to reassure service members, about the vaccine's safety, as a study in the U.K. found. Even efforts at more open communication and education are viewed through a lens of distrust.

The Bottom Line

With my admittedly limited resources (time/access to journals), I tried to do as extensive a search on safety studies of the anthrax vaccine as possible. Report after report stated that the most common reactions to the vaccine tended to be local and of mild to moderate severity, being limited mainly to erythema, edema and pruritis. Severe reactions of these types were rare, and none of the studies found any connection between the vaccine and long-term health issues, like autoimmune disorders or chronic fatigue. My best guess is that chronic issues are most likely unrelated to the vaccine and may be due to other factors (e.g., other environmental causes, stress and/or psychogenic illness, etc.). If they are connected to the vaccine, they seem to be so exceedingly rare that, for individuals at risk of anthrax exposure, the benefits of the vaccine outweigh the remote risks of a serious AE. Of course, research on the anthrax vaccine should continue. For one thing, we should have more than one formulation available. For another, discovering how long the vaccine provides protection and improving that aspect is definitely essential so we can reduce the number of boosters required.

Now, due to the very low risk of exposure to the bacteria for the average U.S. citizen, combined with the high frequency of boosters, I wouldn't recommend the anthrax vaccine for routine use. There just isn't a need; there would be little to no benefit while presenting an increased risk (even if only a slight increase). However, for anyone who is at risk of anthrax exposure, the weight of evidence strongly favors its use. When it comes to the military, this is especially true, since the risk of anthrax as a biological weapon is high. As any student of history can tell you, one of the biggest enemies of an army is not necessarily the opposing force, but rather disease.
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References:

• Brachman PS, Gold H, Plotkin SA, Fekety R, Werrin M & Ingraham NR. (1962). Field evaluation of a human anthrax vaccine. American Journal of Public Health & the Nation's Health. 52(4):632-45. Retrieved July 6, 2012 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1522900/pdf/amjphnation00490-0074.pdf
• Downing J, Greig TW, Quattlebaum MD, Valentin M, Heeren TC & Grabenstein JD. (2007). Assessing the safety of anthrax immunization in US Army aircrew members via physical examination. Journal of Occupational and Environmental Medicine. 49(10)1079-85. Retrieved July 6, 2012 from www.ncbi.nlm.nih.gov/pubmed/18000413
• Murphy D, Dandeker C, Horn O, Hotopf M, Hull L, Jones M, Marteau T, Rona R & Wessely S. (2006). UK armed forces responses to an informed consent policy for anthrax vaccination: a paradoxical effect? Vaccine. 24(16):3109-14. Retrieved July 6, 2012 from http://www.ncbi.nlm.nih.gov/pubmed/16504348
• Niu MT, Ball R, Woo EJ, Burwen DR, Knippen M & Braun MM. (2009). Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007. Vaccine. 27(2):290-7. Retrieved July 6, 2012 from http://www.ncbi.nlm.nih.gov/pubmed/18992783
• Sever JL, Brenner AI, Gale AD, Lyle JM, Moulton LH & West DJ. (2002). Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Pharmacoepidemiology and Drug Safety. 11(3):189-202. Retrieved July 6, 2012 from http://www.ncbi.nlm.nih.gov/pubmed/12051118
• Sever JL, Brenner AI, Gale AD, Lyle JM, Moulton LH & West DJ (2004). Safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Pharmacoepidemiology and Drug Safety. 13(12):825-40. Retrieved July 6, 2012 from http://www.ncbi.nlm.nih.gov/pubmed/15386719
• U.S. FDA. (2012). Anthrax. Retrieved July 6, 2012 from http://www.fda.gov/biologicsbloodvaccines/vaccines/ucm061751.htm
• U.S. FDA. (2012). Summary Basis for Regulatory Action. Retrieved July 6, 2012 from http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM308410.pdf
• U.S. CDC. (2009). Anthrax. Retrieved July 6, 2012 from http://www.cdc.gov/nczved/divisions/dfbmd/diseases/anthrax/
• U.S. CDC. (2000). Surveillance for adverse events associated with anthrax vaccination - U.S. Department of Defense, 1998-2000. Morbidity and Mortality Weekly Report. 49(16):341-5. Retrieved July 6, 2012 from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4916a1.htm
• U.S. CDC. (2010). Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. Morbidity and Mortality Weekly Report. 59(rr06):1-30. Retrieved July 9, 2012 from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5906a1.htm
• Wells TS, Sato PA, Smith TC, Wang LZ, Reed RJ & Ryan MA (2006). Military hospitalizations among deployed US service members following anthrax vaccination, 1998-2001. Human Vaccines. 2(2):54-9. Retrieved July 9, 2012 from http://www.landesbioscience.com/journals/vaccines/wellsHV2-2.pdf