EXTRA!

NOVEMBER 19, 2002

MORE CDC DIRTY WORK ON THE ANTHRAX VACCINE

By Meryl Nass, MD

My comments are interspersed within this item, found in the MMWR (November 15, 2002), a CDC publication. The ACIP is a CDC construct (supposedly independent but not really--the same group that said only 15,000 Americans should get smallpox vaccine at first, then changed their recommendations to make them more in line with government desires.)

What is this article really about? It is a justification for changes to an earlier ACIP document that suggested avoiding anthrax vaccine in civilians, providing cover to government policies (promulgated by CDC) that now wish both to test and to use anthrax vaccine in civilians.

CDC did not get enough takers for its vaccine trial last winter to change the vaccine label, and so this piece is spearheading a new attempt to enroll civilians in unethical and inappropriate anthrax vaccine research.

CDC had hoped its post-exposure vaccine trial would enroll enough civilians, especially pregnant women and children, to further test the vaccine. Why do they need civilians, when over 500,000 military personnel have already been vaccinated since 1998? Because even FDA has admitted the army studies are simply no good, and are unacceptable for approving changes to the vaccine license desired by our friends at CDC/DOD.

*Read The CDC article.

Notice to Readers: Use of Anthrax Vaccine in Response to Terrorism: Supplemental Recommendations of the Advisory Committee on Immunization Practices

In December 2000, the Advisory Committee on Immunization Practices (ACIP) released its recommendations for using anthrax vaccine in the United States (1). Because of recent terrorist attacks involving the intentional exposure of U.S. civilians to Bacillus anthracis spores and concerns that the current anthrax vaccine supply is limited, ACIP developed supplemental recommendations on using anthrax vaccine in response to terrorism. These recommendations supplement the previous ACIP statement in three areas: use of anthrax vaccine for pre-exposure vaccination in the U.S. civilian population, the prevention of anthrax by postexposure prophylaxis (PEP), and recommendations for additional research related to using antimicrobial agents and anthrax vaccine for preventing anthrax.

Use of Anthrax Vaccine for Pre-Exposure Vaccination

In December 2001, the U.S. Department of Health and Human Services obtained a limited supply of anthrax vaccine (BioThrax [formerly Anthrax Vaccine Adsorbed (AVA)], BioPort, Lansing, Michigan), allowing ACIP to reconsider using anthrax vaccine in the U.S. civilian population. ACIP reaffirms that pre-exposure use of anthrax vaccine should be based on a quantifiable risk for exposure (1). ACIP recommends that groups at risk for repeated exposures to B. anthracis spores should be given priority for pre-exposure vaccination. Groups at risk for repeated exposure include laboratory personnel handling environmental specimens (especially powders) and performing confirmatory testing for B. anthracis in the U.S. Laboratory Response Network (LRN) for Bioterrorism Level B laboratories or above, workers who will be making repeated entries into known B. anthracis-spore--contaminated areas after a terrorist attack (2), and workers in other settings in which repeated exposure to aerosolized B. anthracis spores might occur. Laboratory workers using standard Biosafety Level 2 practices in the routine processing of clinical samples or environmental swabs (Level A laboratories [3]) are not considered by ACIP to be at increased risk for exposure to B. anthracis spores.

For persons not at risk for repeated exposures to aerosolized B. anthracis spores through their occupation, pre-exposure vaccination with anthrax vaccine is not recommended. For the general population, prevention of morbidity and mortality associated with anthrax will depend on public vigilance, early detection and diagnosis, appropriate treatment, and PEP.

Prevention of Anthrax by PEP

Because of a potential preventive benefit of combined antimicrobial PEP and vaccine and the availability of a limited supply of anthrax vaccine for civilian use, ACIP endorses CDC making anthrax vaccine available in a 3-dose regimen (0, 2, 4 weeks) in combination with antimicrobial PEP under an Investigational New Drug (IND) application with the Food and Drug Administration for unvaccinated persons at risk for inhalational anthrax. However, anthrax vaccine is not licensed for postexposure use in preventing anthrax.

Use of anthrax vaccine for PEP could have additional benefits, including reducing the need for long-term antimicrobial therapy with its associated problems of nonadherence and possible adverse events. After the anthrax-related terrorist attacks in 2001, approximately 10,000 persons were recommended to receive a 60-day regimen of antimicrobial prophylaxis for suspected or confirmed exposure to B. anthracis spores, but adherence to the recommended 60-day antibiotic regimens was as low as 42% (4).

CDC is trying to exploit the fact that over 40% of people given antibiotics after possible anthrax exposure did not take the full course, by twisting this observation into support for anthrax vaccine. So they claim that given this noncompliance, "the effectivenenss of antimicrobial prophylaxis in such persons is unclear." This is utter nonsense, because even without full compliance, antibiotic treatment was in fact 100% effective. That's right, 100%! It's not unclear at all.

In addition, because studies of the 2001 terrorist attacks suggest that some persons might be exposed to B. anthracis spores in excess of those studied in animal models, the effectiveness of antimicrobial prophylaxis in such persons is unclear (4). However, no cases of anthrax have been detected among persons recommended to take antimicrobial prophylaxis after the terrorist attacks of 2001.

They just admitted antibiotics were effective. The writer then proceeds to ignore it.

The provision of anthrax vaccine for PEP under an IND application should provide an opportunity to reduce the risk to the greatest extent possible with current medical knowledge and might provide data to support developing additional recommendations for preventing anthrax.

Here they begin to hint at what is pushing this recommendation: the goal is to generate data to expand the vaccine's license, with further human experiments.

To better document the immunogenicity of anthrax vaccine in the postexposure setting, ACIP encouraged CDC to obtain serologic testing on a subset of vaccinees.

ACIP recommended previously that if antimicrobial therapy is used alone for postexposure prevention of anthrax, at least a 30-day course of treatment should be provided. Previous recommendations noted that longer courses (42--60 days) might be indicated. On the basis of limited data from both unintentional human exposures and animal studies (5--7), ACIP now recommends that the duration of postexposure antimicrobial prophylaxis should be 60 days if used alone for PEP of unvaccinated exposed persons.

Data are insufficient to clarify the duration of antimicrobial use in combination with vaccine for PEP against anthrax. Antibody titers among vaccinated persons peak at 14 days after the third dose (8). If antimicrobial prophylaxis is administered in combination with postexposure vaccination, it might be prudent to continue antibiotics until 7--14 days after the third vaccine dose.

Few data exist about the effectiveness of postexposure antimicrobial prophylaxis among exposed persons who have been partially or fully vaccinated. In the only human clinical trial of anthrax vaccine, cases occurred among participants who had received <4 doses (9).

Here a federal agency admits, for the first time, that maybe three doses are NOT enough! In the only trial of (another) anthrax vaccine--the Brachman trial--at least three people developed anthrax after receiving three vaccine doses. (But so what? CDC picked three doses and they're sticking to that number.)

Recognizing these limited data, but considering a potential undefined benefit, ACIP recommends that persons who have been partially or fully vaccinated receive at least a 30-day course of antimicrobial PEP and continue with the licensed vaccination regimen. Antimicrobial PEP is not needed for vaccinated persons working in Biosafety Level 3 laboratories under recommended conditions (10) nor for vaccinated persons (six vaccinations according to the current label) wearing appropriate personal protective equipment (PPE) while working in contaminated environments in which inhalational exposure to B. anthracis spores is a risk, unless their respiratory protection is disrupted.

Additional Considerations

For most occupational settings, recommendations about anthrax vaccine and antimicrobial PEP might be implemented in combination with use of appropriate PPE (2). In addition to receiving PEP for preventing anthrax, potentially exposed persons should be observed for signs of febrile illness. CDC has published guidelines on clinical evaluation of persons with possible anthrax, including antimicrobial treatment (1,2).

And now we interrupt this message to bring you the commercial:

Because the current vaccine supply is limited, ACIP recommends expanded and intensive efforts to improve anthrax vaccine production.

Recommendations for Additional Research

Because of the absence of data to guide public health recommendations in these critical areas, ACIP recommends studies on the safety and immunogenicity of anthrax vaccine for use in children, additional studies on the safety of anthrax vaccine during human pregnancy, and reproductive toxicology studies on anthrax vaccine in laboratory animals.

CDC has previously admitted this extremely disturbing fact: No data have been obtained on the effect of anthrax vaccinations in pregnant lab animals. Humans were the first species CDC wanted to study the vaccine on, and they made a special effort to recruit pregnant civilians for their anthrax vaccine trial last winter. I believe this is unethical. That is because the Navy has done a study indicating that anthrax vaccination during the first trimester of pregnancy increases birth defects. A preliminary report was published last year (in the MMWR, vol 51, number 6) but the Navy has been tasked with doing an enormous amount of additional work to justify its original conclusion, before it can publish a full report. Until then, CDC and its cronies are pretending the study never happened. (The Army studies that claimed the vaccine was safe never had to do any confirmatory research, unsurprisingly.)

To strengthen public health recommendations for PEP, ACIP recommends expanded animal studies to evaluate further the effectiveness of antimicrobial prophylaxis with and without anthrax vaccine, define the optimal duration of antimicrobial PEP for the prevention of inhalational anthrax, and evaluate alternative antimicrobial PEP regimens. Additional research also should be directed toward developing an improved vaccine for preventing anthrax and new therapeutic strategies, including use of antitoxin (e.g., hyperimmune globulin) for treating anthrax.

I tried to get the Defense Department to stockpile anthrax immune globulin beginning in 1990, and am glad they finally got the message in time for Gulf War 2. An effective anti-anthrax globulin will likely save many exposed persons, even after they get ill. I think one of the impediments to this treatment was that having immune globulin available meant anthrax disease might not be fatal after all, negating the need for vaccinating all the troops.)

References

1. CDC. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(No. RR-15).
2. CDC. Occupational health guidelines for remediation workers at Bacillus anthracis--contaminated sites---United States, 2001--2002. MMWR 2002;51;786--9.
3. CDC. Biological and chemical terrorism: strategic plan for preparedness and response: recommendations of the CDC Strategic Planning Workgroup. MMWR 2000;49(No. RR-4).
4. Shepard CW, Soriano-Gabarro M, Zell ER, et al. Antimicrobial postexposure prophylaxis for anthrax: adverse events and adherence. Emerg Infect Dis 2002;8:1124--32.
5. Meselson M, Guillemin J, Hugh-Jones M, et al. 1994. The Sverdlosk
anthrax outbreak of 1979. Science 1994;226:1202--7.
6. Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis 1993;167:1239--42.
7. Henderson DW, Peacock S, Belton FC. Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. J Hyg 1956;54:28--36.
8. Pittman PR, Kim-Ahn G, Pifat DY, et al. Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans. Vaccine 2002;20:1412--20.
9. Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M, Ingraham NR. Evaluation of human anthrax vaccine. Am J Public Health 1962;52:632--45.
10. CDC. Biosafety in microbial and biomedical laboratories, 5th ed. In: Richmond JY, McKinney RW, eds. Washington, DC: U.S. Department of Health and Human Services, CDC, 2001.