Smallpox vaccine in flux for doctors

The risk of exposure to smallpox is too small-and the risk posed by the vaccine too great – to justify vaccinating most physicians at this time, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended at its annual summer meeting.

In the absence of an act of smallpox bioterrorism, ACIP advised against vaccinating physicians other than those on designated smallpox response teams and selected health care personnel in facilities to be designated as smallpox referrals centers.

CDC officials estimated at the meeting that perhaps 15,000-20,000 people would be vaccinated under this plan. The ACIP recommendations included no numbers, however, and news reports have since said this figure could include 500,000 people.

The 500,000 (figure) could be right, it could be high, or it could be low, Health and Human Services spokesman said in an interview. The CDC and the HHS are reviewing the ACIP’s recommendations. Also, reports that smallpox vaccination is set to begin this fall are speculative. There is no timetable.

The debate also may shift as a result of a Yale University report published online July 15 in the Proceedings of the National Academy of Sciences.

This epidemiologic modeling study suggests that the "ring" vaccination approach would likely result in far more cases and deaths than if mass vaccination were applied in the event of a smallpox bioterrorist attack in a large US city. Ring vaccination was used to eradicate wild cases of smallpox. In ring vaccination, the case’s household members and other close contacts and their contacts are vaccinated.

In its recommendations, ACIP advised that, in the absence of an outbreak, smallpox response team, trained to investigate suspected smallpox cases and establish control measures, would be vaccinated. Teams might include medical epidemiologists, laboratory scientists, and security/law enforcement personnel. Each state would establish one or more such teams – no numbers have been decided as yet.

Smallpox referral centers would provide care to smallpox cases, and selected physicians, nurses, and possibly other support personnel at those centers would receive the vaccine under this plan.

A few hundred laboratory workers who handle recombinant vaccinia viruses or other orthopoxviruses are now vaccinated against smallpox. Also, about 300 volunteers are receiving diluted vaccine in a federal research study.

The ACIP acknowledge that the first smallpox cases could present to any physician, including physicians in an office setting. But, in the absence of an outbreak, the committee found that the risk of vaccinating all physicians exceeds the benefits.

If an unvaccinated health care provider were to be exposed to smallpox, postexposure vaccination is highly protective if given within a week. One of the built-in assumptions of the new recommendations is that the overall risk of exposure to any individual provider anywhere in the United States is even more remote and is outweigh by the large number of vaccine side effects.

The American College of Physicians-American Society of Internal Medicine’s liaison to the ACIP, pointed out that a recipient of smallpox vaccine, which is made from live vaccinia virus, may infect others for a week or two following vaccination.

A vaccinated physician would therefore pose a risk to patients during that time. The chances that any one physician will encounter smallpox are slim and far less than the chances of side effects or of harm to patients.

The risk is more acceptable, however, for the designated response and health care teams. Their risk of exposure would reach 100 percent if an outbreak were to occur in their region.

Further, postexposure vaccination is an acceptable approach. People don’t transmit smallpox without first developing a rash following a 7-17 day prodrome. People infected with smallpox are probably not on the subway or on a plane. They’re home in bed. The most likely place to contract smallpox is at home or in a hospital. It’s not like measles, where you can get it from someone before they’re sick.

Further, the rush to vaccinate may be risky. Smallpox vaccine carries a far higher risk than available routine vaccines. Based on data from the late 1960’s, the estimated all-cause death rate following receipt of smallpox vaccine was about five deaths per one million in children less than one year of age, 0.5 deaths per one million in children age 1-19 years, and possibly five deaths per one million in adults, according to a professor emeritus of pediatrics at the University of Arizona, Tucson.

Postvaccinial encephalitis occurred in about two-six per one million vaccines. Vaccinia necrosum was seen in about one per million children and probably would be far more common among adults. Thousands of other adverse events, such as eczema vaccinatum, generalized rashes, and accidental implantation occurred in the past and would likely be much more common today given the larger number of people living with altered immune systems.

Another complicating matter is that none of the smallpox vaccines are licensed. In October 2001, the federal government contracted with Acambis Inc. to produce at least 209 million doses of two different smallpox vaccines derived from cell culture. Licenser of those vaccines is expected in late 2003 or 2004.

Until then, only two investigational-status smallpox vaccines – Wyeth’s Dryvax and Aventis Pasteur Inc.’s smallpox vaccine – may be used, and only with signed informed consent from vaccine recipients. Also still in investigational status are doses of vaccinia immune globulin for use in treating the 600 or so adverse events expected to occur with the vaccination of four million to six million people.

In contrast to most of ACIP’s vaccine policy decisions, this one was made without a key piece of information: the risk of exposure. While the threat of smallpox bioterrorism probably hasn’t increased since ACIP’s last smallpox response statement in June 2001, the perception of threat has increased since September 11.