Ring of Fire: CDC plan to immunize around first smallpox cases has the devil in the details

Used successfully to eradicate smallpox in 1980

Bioterrorism Watch

Should a bioterrorist strike with smallpox, the Centers for Disease Control and Prevention’s (CDC’s) recently released response plan calls for investigators to rapidly immunize a "ring" around the first cases. The ring concept calls for isolation of confirmed and suspected smallpox cases followed by contact tracing, vaccination, and close surveillance of contacts.

"Ring vaccination — sometimes called search and containment —- is identifying individuals with confirmed smallpox and then identifying and locating those people who came in contact with that person, and vaccinating those people in outward rings of contact," says Harold Margolis, MD, CDC senior adviser for smallpox preparedness. "This produces a buffer of immune individuals and was shown to prevent smallpox and to ultimately eradicate this disease."

Indeed, the ring approach was used to successfully eradicate smallpox from the world in 1980. The only officially acknowledged stocks of live virus remaining are in the United States and Russia, but bioterrorism experts have long feared that smallpox may have fallen into other hands.

But the ring concept was effective when the demographics of smallpox were very different, when few were infected and the vast majority of people were already immune. The CDC plan acknowledges as much, noting that several current factors could contribute to a more rapid spread of smallpox than was routinely seen before this disease was eradicated.

These factors include virtually nonexistent immunity to smallpox, increased mobility of the population, and delayed recognition of smallpox by health personnel who are unfamiliar with the disease, the plan states. Concerning the latter — similar to the fine line between initial symptoms of anthrax and influenza — one of the most confounding differential diagnoses for smallpox is chickenpox. (See "Smallpox or chickenpox? How to make the diagnosis," in this issue.)

Preemptive strike

While the ring strategy is a classic public health approach, some favor a more aggressive preemptive action in this new age of bioterrorism: Immunize response teams of health care workers throughout the nation.

"I would be in favor of a plan to prospectively immunize not only the strike force at the federal level, but [also] a cadre of people in each state," says William Schaffner, MD, chairman of preventive medicine at Vanderbilt University in Nashville.

Having groups of health care workers immunized in advance could also be critical if the "ring" is difficult to perceive, he notes.

"We think of it conceptually as a ring, but clearly people are not all in one geographic area," he says. "The people who may or may not have contact with this first case will be scattered all over the community. They went shopping there, had a church group here, and then they played bridge. The first thing we will be looking for is information from public health authorities about who is within the ring and who is outside the ring. If that is not articulated with great clarity everybody is going to be in deep trouble."

The CDC is certainly aware of such issues and concerns, and discussions are still ongoing within the agency about preemptively immunizing some health care workers. "We have to weigh the risks and benefits of vaccination for any group, and that would include health care workers. We are kind of working through those issues right now," Lisa Rotz, MD, medical epidemiologist in the CDC Bioterrorism response program, tells Bioterrorism Watch.

The overriding factor in holding back immunization of health care workers is the hazards and side effects of the vaccine.

"In 1972 we actually discontinued routine vaccination [in the United States] because the risks of adverse events from the vaccine outweighed the risk of any one person coming down with smallpox, even though it was still occurring in other parts of the world," Rotz says. "I think that still holds true here. We are dealing with a vaccine that presents problems in and of itself."

Indeed, death occurs in about one per million primary vaccinations, usually as a result of progressive vaccinia, post-vaccinal encephalitis, or severe eczema vaccinatum. Other adverse events include inadvertent inoculation from the vaccinated site (e.g., to the eyes).

CDC will bring vaccine within hours’

In addition, the CDC has immunized approximately 100 of its personnel, who could be dispatched immediately to a stricken area and begin investigating and administering vaccine.

"We have people trained to respond to smallpox who can go rapidly to an area to evaluate a case, and then help the local and state officials begin implementing control measures," Rotz says. "That would include helping them implement surveillance, making sure we have identified people who need to be vaccinated right away and to start setting that up. We would get things started there until they get their own response up and running."

But instead of immunizing health care workers in advance, the CDC plan is to administer the vaccine after a case occurs. The CDC could deliver personnel and vaccine within "hours" to any area in the country, Rotz says. Moreover, the vaccine can be effective up to four days after infection sets in, and may prevent death in the patient.

Among the top priority for immunizations after smallpox is reported are "those involved in the direct medical care, public health evaluation, or transportation of confirmed or suspected smallpox patients," the CDC plan states. (See "Health workers, contacts priority for vaccination," in this issue.) In addition, smallpox patients would be placed under airborne precautions similar to that used for tuberculosis patients, who are placed in negative pressure rooms (vented outside) and treated by workers with respirators.

Another important factor in favor of the CDC approach is that smallpox is not communicable in its incubation period, says D.A. Henderson, MD, director of the office of public health preparedness at the Department of Health and Human Services in Washington, DC.

"You have an incubation period of 10 to 12 days when the individual feels perfectly well and is not able to transmit infection," he says. "Then he gets a fever for a couple of days and then the rash. It’s only when the rash begins that the individual transmits the disease. So, in fact, [those are] the people we’re really concerned about isolating so that they don’t transmit the disease. But just because somebody’s infected does not mean that they’re going to transmit infection during that incubation period. They won’t do that."

Into the thousands very quickly

Still, while emphasizing that the CDC plan is a good starting point, Schaffner argues that it would make sense — and allay subsequent chaos — to immunize groups of health care workers before an event occurs.

"The immediate [CDC] public health strike team is like being out on the beach and walking in up to your ankles, but the next step you take gets you into water over your head," he says. "Because if you start thinking about [immunizing health care workers], you’re talking about emergency personnel, ambulance drivers, infectious disease doctors, [and] nurses in hospitals who would be designated to care for such patients. It could get into the many thousands very quickly."

In addition, with the exception of the recently trained CDC personnel, few clinicians in the country know how to administer the smallpox vaccine using the "little pitchfork" bifurcated needle.

"That is one potential benefit of vaccinating a group of first responders around the country," Schaffner says. "You train these people how to administer the vaccine and all of sudden you have a bunch of trained people out there that we haven’t had before. I think that would be a substantial additional benefit."