Alternative Smallpox Strategies: A Newsmaker Interview With Thomas Mack, MD, MPH

Laurie Barclay, MD

Dec. 19, 2002 — Editor's Note: In the wake of U.S. President Bush's newly released vaccination plan, the New England Journal of Medicine offered an accelerated online release of articles "to inform the current national debate about smallpox vaccination." Included in these articles, which will be published in the Jan. 30, 2003, issue, is a Sounding Board by Thomas Mack, MD, MPH, a professor of preventive medicine at the Keck School of Medicine, University of Southern California at Los Angeles.

President Bush's plan calls for vaccination of 500,000 healthcare providers initially followed by up to 10 million others, but Dr. Mack suggests alternatives to this plan and their likely ramifications. Although Dr. Mack is now a cancer epidemiologist, he was involved in observing and investigating the dynamics of smallpox transmission in Pakistan 30 years ago. Medscape's Laurie Barclay interviewed Dr. Mack to learn more about his recommendations for smallpox vaccination and containment strategies.

Medscape: What is your opinion of the current smallpox vaccination plan?

Dr. Mack: I agree that we should not have mass vaccination of the public, but I disagree that we should vaccinate half a million healthcare workers. The

introduction of smallpox could occur anywhere within the U.S. — the likelihood that hospital workers would be the first to come in contact with the index case is not that great, so what is the rationale behind vaccinating large numbers of hospital workers?

Vaccinating large numbers of staff identified by the hospitals as well as the general public is a mistake, because the deaths from vaccine complications will outweigh any limited increase in protection. Mass vaccination will guarantee a few deaths. If you vaccinate a million people, you will have three deaths from vaccine complications if those you vaccinate are healthy, more if they are immunosuppressed or chronically ill. And the liability for complications from vaccination is not clear.

Medscape: Wouldn't barrier dressings help cut down on complications due to secondary infection from the vaccination site?

Dr. Mack: Barrier dressings are extremely uncomfortable and have to be worn for 10 days. When you're talking about half a million people, that is just not going to happen. Doctors and nurses will have to remove those dressings just to do their daily grind, and in the process, they'll come in close contact with lots of very vulnerable immunosuppressed patients. Those patients with skin lesions from AIDS or dermatological conditions will be at greatest risk of secondary infection from the caregiver's vaccination site.

Medscape: Could vaccinia immunoglobulin (VIg) help reduce vaccine-related complications?

Dr. Mack: Patients who develop serious complications from vaccination, like eczema vaccinatum, will die if they're not treated with VIg. It has never been widely used as adjunct prophylaxis, but in a small randomized trial in Madras, VIg increased the effectiveness of vaccination by 70%. So it may have a role in prophylaxis, and it's important to have enough on hand. Right now we have very little, but the CDC is working on trying to increase the available supply.

Medscape: Do you recommend any alternatives to widespread vaccination of healthcare workers?

Dr. Mack: A better plan is to vaccinate a team of specified field investigators, paramedics, caregivers, diagnostic lab technicians and some law enforcement officers, and to mobilize them to wherever they are needed in the event of an outbreak. About 15,000 individuals would be needed. These teams should be prepared and supervised by public health agencies because they have the expertise and the experience to do it.

Medscape: Would this plan protect us if a suicidal bioterrorist deliberately tries to infect as many people as possible?

Dr. Mack: In the early stages of the disease, a terrorist won't be infectious. Before the rash appears, individuals with smallpox are not really infectious, even though virus can be cultured from the pharynx. The most infectious individuals are very sick and have a very obvious rash that is virtually

impossible to miss. The most infectious period is during the second half of the first week of rash, when symptoms are so severe that the infected person is bedridden. So the likelihood of a bioterrorist wandering around and infecting others without being recognized as having smallpox is remote.

Smallpox is not aerosolized easily, so saliva droplets containing the virus fall on the floor or on the clothes and basically stay there. However, there was one outbreak in a hospital thought to be due to airborne spread through a faulty ventilation system that recycled air from an infected patient's room to other rooms, and another case of hospital transmission thought to be related to infected linens.

Medscape: Isn't it commonly believed that the pilgrims infected Native Americans with smallpox by giving them infected blankets?

Medscape: If we do have an outbreak, what is your recommendation for containment?

Dr. Mack: The first wave of infection will probably be people who are admitted to the hospital before they are diagnosed, while they have the fever but before they get the rash. The first case of smallpox will probably end up in a hospital. But the rest should not be admitted to a general hospital, assuming they are diagnosed before they enter the hospital. They should go to a dedicated facility or stay at home until [a dedicated facility] is available. There really is not much you can do for a smallpox patient other than symptomatic care.

Medscape: Please elaborate on your suggestion for dedicated facilities.

Dr. Mack: Every public health agency should think about selecting a small facility in advance, which, when needed, could be dedicated to isolation and treatment of individuals infected with smallpox. This could be a hospice, a nursing home, or even a National Guard field hospital. During the outbreak, the facility would be manned by a previously selected, previously vaccinated team.

Medscape: Do you see any practical problems with this arrangement, such as refusal of the chosen facility to convert to a smallpox ward, financial collapse of the facility before the outbreak because of loss of patients and staff once it was so designated, and lack of resources to convert the facility sufficiently quickly?

Dr. Mack: A public health officer has the authority to take over a hospital, so the facility couldn't really refuse to take part in this plan. Arrangements could be made in advance with the owner to offer remuneration to move the patients and staff out of the facility during an outbreak, and perhaps to continue paying the staff while they were off the premises. Before the outbreak, which facility had been designated could be kept quiet, and after the outbreak was over, the facility could resume its usual operations. Smallpox isn't like anthrax — it's easy to clean up.

Medscape: What about contacts of the index case?

Dr. Mack: For the first case, the Public Health Department would send out investigators to find all of the contacts of the index case from the time of fever through the time of the rash. In Pakistan, we saw first-hand that it's the social contacts of the infected individuals who are at risk, not necessarily those who live in the same geographic area. If we have an outbreak in the U.S., each of the potentially exposed persons would be contacted every day for 20 to 30 days to see if they develop any symptoms, so that they could be properly isolated and treated if necessary. If they chose not to cooperate, they should be forced to cooperate to avoid further transmission. This is one of the few situations that should be mandatory rather than voluntary. But in all likelihood, these individuals would be frightened and would willingly cooperate if treatment is made available to them. This treatment should include VIg after vaccination.

Medscape: How effective do you think this plan would be?

Dr. Mack: Smallpox is contagious but it doesn't spread like wildfire. We have one to three weeks to isolate exposed individuals before they become contagious. If we follow this plan, the second wave of smallpox will develop under surveillance. Of course, the system wouldn't be completely efficient, but any case missed would be like a new importation, and surveillance of the contacts of that case would help prevent additional spread. Smallpox is a disease that lends itself to containment. Based on what we learned in Europe, an initial smallpox introduction will probably result in fewer than 20 cases and 10 deaths. Hopefully, with increased experience, each subsequent introduction would have less of an effect.

The authorities and the media have done a terrible job of preparing the public because now they're scared to death, when in fact the disease is controllable and shouldn't create mass panic. In the European outbreak of smallpox after World War II, for every one case admitted to the hospital, there were about six hospital patients and visitors who became infected, about four hospital workers, about three household contacts, and only one individual where the route of transmission was unclear. Hospitals are where the danger is, not being out in public.

Of about 1,000 individuals infected in the postwar European outbreak, not one was infected on a plane, train, or bus. So the notion that we're at risk from infected individuals traveling around is a mythical fright.

N Engl J Med. 2002;348(5):000-000

Reviewed by Gary D. Vogin, MD