BMJ  2004;329:524-525 (4 September), doi:10.1136/bmj.329.7465.524

Editorial

Bioterrorism and compulsory vaccination

Better vaccines are needed if vaccination is to be made compulsory

Taken at face value the use of vaccines to prevent the effects of serious infections caused by a terrorist attack appears a sensible policy. In 1997 the United States Department of Defense initiated the compulsory anthrax vaccine immunisation programme to immunise 2.4m military personnel.¹ In December 2002 a similar programme, also involving civilians, was started against smallpox. In the first five and half months the Department of Defense administered 450 293 doses of smallpox vaccine.² United States military personnel engaged in military operations in Iraq are immunised against smallpox and anthrax. As in any vaccination campaign, the incidence of the target disease and the characteristics of available vaccines are two key elements in decision making.

Naturally occurring anthrax is a rare disease. It occurs mostly in cutaneous form among those exposed to animal products (such as hides) and causes a rare and rapidly fatal—if untreated—respiratory illness (inhalation anthrax). Inhalation anthrax is the most likely form of the disease in the event of a terror attack as the use of anthrax spores for terror or warfare would probably follow dissemination at high concentration by aerial route. As smallpox was eradicated three decades ago, mass use of both vaccines in an antiterrorist role has an epidemiological justification only in the presence of a credible threat—the capability to produce and deliver large quantities of active agents to susceptible populations and the will to carry out such an action. Many suspected (and now know) that these conditions did not exist in the Iraq deployment and in the mountains of Afghanistan. The only recent recorded use of an infectious agent in a terrorist role (the anthrax mailing campaign in the United States) used bacteria that had been sourced from a US military establishment.³

Both anthrax and smallpox vaccines have been in use for a long time, but there are few other similarities between them. The UK and US anthrax vaccines consist of alum precipitated cell-free filtrate of bacilli. The US vaccine (BioThrax), manufactured by the BioPort Corporation (Lansing, Michigan), is adsorbed onto aluminium hydroxide (so called adsorbed anthrax vaccine, or AVA). At present, in the USA VaxGen and Battelle are developing and testing a recombinant Bacillus anthracis vaccine candidate known as rPA102.⁴

Evidence of the effectiveness of the predecessor vaccine to AVA relies on a 1950s study carried out by Brachman et al on 1249 adult workers in four tanneries in the north east of the United States.⁵ The study showed that the killed vaccine was 92.5% effective in preventing cases of cutaneous anthrax. Separate effectiveness estimates for cutaneous and inhalation forms were not reported, but the small numbers of inhalation anthrax found in the study left the authors unable to infer a protective benefit. This conclusion was based on the observation that during a concurrent epidemic no worker in the immunised arm of the study contracted the inhalation form of the disease, whereas four out of five infected workers in the placebo arm died. As the quality of reporting of the study is in keeping with its age, it is unclear whether random allocation to either arm did take place.⁶ Despite the authors' conclusion, the website of the anthrax vaccine immunisation programme of the Department of Defense claims proved protection against inhalation anthrax.⁷

Workers in the intervention arm of the Brachman study⁵ had a higher rate of adverse events than in the placebo arm, but no large scale trial of AVA has ever been conducted. Live attenuated anthrax vaccines were tested in the then Soviet Union in the mid-70s and seemed effective against cutaneous anthrax.⁶

The current smallpox vaccinia virus vaccine (Dryvax) produced in the United Kingdom on behalf of the US government has remained virtually unchanged since the days of the eradication campaign.⁸ It is thought to have substantial potency when administered to previously unvaccinated adults,⁸ but the harm profile of the vaccine reflects its live attenuated content, with post-vaccination encephalitis occurring in around 2.9 cases per million primary vaccinated subjects.⁹ In one study of 450 293 inoculations up to 3% of vaccine recipients needed short term sick leave. One case of encephalitis and 37 cases of acute myopericarditis developed after vaccination. No deaths were observed, and all patients recovered.^{2 9-11} Newer vaccines are currently being developed but are a long way from field testing.⁷ Trials of an improved version of Dryvax vaccine (ACAM2000) comparing the two vaccines head to head have recently been halted because of the occurrence of myocarditis in three of the 1132 volunteer participants.¹² It is unclear in which of the arms and in what proportions the events took place.

The US effort to prevent the effects of infectious agents by vaccination seems to be based on an unproved threat and the availability of old vaccines for which relatively few controlled data exist. Whether a credible threat will provide a rationale for the use of current vaccines in future confrontations is not known. Intelligence or its interpretation by politicians has proved to be fallible. Attention has been paid to the surveillance of recipients of both types of vaccines, but such methods are no substitute for large, well designed field trials powered to detect both serological responses and rare but potentially important adverse events. Although field trials are expensive, logistically difficult to undertake, and unlikely to answer the issue of vaccine effectiveness during a terror attack, investment in evaluation and in better and safer vaccines surely must be a requisite to have credible compulsory immunisation programmes involving huge numbers of adults of reproductive age. Until such time, the choice of whether to be vaccinated or not should be left to the individual.

Cochrane Vaccines Field, Via Adige 28a, 00061 Anguillara Sabazia, Rome, Italy (Toj1{at}aol.com)

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Competing interests: TJ is in receipt of retired pay and a war pension from the Ministry of Defence of the United Kingdom.

References

1. Nass M. Anthrax vaccine. Model of a response to the biologic warfare threat. Infect Dis Clin North Am 1999;13: 187-208.[CrossRef][ISI][Medline]
2. Grabenstein JD, Winkenwerder W Jr. US military smallpox vaccination program experience. JAMA 2003;289: 3278-82.[Abstract/Free Full Text]
3. The insider. After months of bungled investigation, it now looks certain that America's anthrax attacks came from within. The implications are terrifying. New Scientist 2002 February 9. (New Scientist.com).
4. VaxGen reports phase i clinical trial results of anthrax vaccine candidate. www.corporate-ir.net/ireye/ir_site.zhtml?ticker=VXGN&script=410&layout=-6&item_id=500806 (accessed 1 Jul 2004).
5. Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M, Ingraham NR. Field evaluation of a human anthrax vaccine. Am J Public Health 1962;52: 632-45.
6. Jefferson T, Demicheli V, Deeks J, Graves P, Pratt M, Rivetti D. Vaccines for preventing anthrax. Cochrane Database Syst Rev 2000;(2): CD000975.
7. Anthrax Vaccine Immunization Program. Anthrax. The vaccine. www.anthrax.osd.mil/vaccine/protect2.asp (accessed 4 Mar 2004).
8. Frey SE, Newman FK, Cruz J et al. Dose-related effects of smallpox vaccine. N Engl J Med 2002;346: 1275-80.[Abstract/Free Full Text]
9. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccinations, 1968: national surveillance in the United States. N Engl J Med 1969;281: 1201-8.
10. Anonymous. Cardiac adverse events following smallpox vaccination—United States, 2003. MMWR Morb Mortal Wkly Rep 2003;52: 248-50.[Medline]
11. Anonymous. Update: adverse events following smallpox vaccination—United States, 2003. MMWR Morb Mortal Wkly Rep 2003;52: 278-82.[Medline]
12. Witte G, Gillis J. Recruitment of smallpox test volunteers halted. Vaccine's potential side effect prompts biodefense contractor's precaution. Washington Post 2004 April 14:E01. www.washingtonpost.com/wp-dyn/articles/A9604-2004Apr13.html (accessed 28 Apr 2004).

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