Smallpox update: be prepared to talk with parents

August 2002

---Philip A. Brunell, MD

The ACIP meeting in June was devoted to a discussion of smallpox. The panel decided there should not be routine vaccination of the population but that vaccination be restricted to those who might respond to or care for suspected cases of smallpox. In the event of an introduction, there would be “ring vaccination,” that is, vaccination of primary contacts and their household contacts.

One of the interesting paradoxes is the public demand for the vaccine. Did you ever think you would have to fight off people who wanted to be vaccinated?

It is not surprising that the public and the medical community have divergent opinions on smallpox vaccine. Reports of irregularities in clinical trials and suspicion of drug company motives in promoting immunization have fueled mistrust. The government handling of the anthrax problem has also cast some doubt on the competence of those to whom we look for leadership. (I will not go into some of the other governmental failings we are witnessing.) One of the reasons that likely has contributed to this divergence is that we have done a good job of encouraging parental involvement in immunization by open discussion. It is important that we continue to engage in an informed dialogue. This dialogue probably will consume more time than other immunizations as this is a different vaccine that would be given for a disease that we had eradicated a quarter of a century ago. Moreover, we are uncertain of our risk of being exposed by a terrorist attack.

The problem is compounded by the dearth of people outside of CDC and their alumni who have had experience with the diagnosis and management of smallpox or with vaccination.

It is particularly painful to see statements that this vaccine is “more dangerous than other vaccines.” Vaccines are not dangerous. Vaccinia is.

The vaccine we will be using initially would probably never have passed the safety requirement now in place. It was grown on the bellies of calves not in sterile tissue culture or embronated eggs as are the vaccines now in use. The hazards of taking the vaccine were acceptable given the alternative: accepting deadly smallpox epidemics that would claim almost half a million lives annually. About a quarter of a century ago, when the risk of vaccination appeared to be greater than the risk of smallpox, a decision was made to stop vaccinating.

Patients at risk

Inoculating with vaccinia produces an infection that is intended to produce less morbidity than would smallpox. It and oral polio were the only vaccines that spread from the vaccines to their contacts. Thus, it not only puts the vaccinee at risk but also those to whom he/she may be exposed. Because vaccinia is a live virus and produces an infection, it requires an immunologically intact host who can terminate the vaccine virus infection and develop a protective response against a future exposure. The most serious reactions are seen in those with cellular immune defects that often are unable to stop the infection with vaccinia. In the “olden days,” these reactions were seen in those with congenital immune deficiencies. Now, we have an increased number of people at risk because of those who have received transplants, are HIV positive or are recipients of immunosuppressive drugs. Unfortunately, there are a substantial number of HIV-positive individuals who are unaware they are infected.

The other group of patients at risk is those with eczema. Controlled eczema does not eliminate the risk of eczema vaccinatum. Thus, if you are a vaccinated health care worker, yourself in good health, it would be important not to expose individuals at high risk until the crust has fallen off your vaccination site. Encephalitis accounts for most of the deaths from vaccination, which are estimated to be from one to as many as five per million. Immunizing the entire population would lead to several hundred deaths. This is a far greater risk than of any vaccine currently in use. This is why I consider this a dangerous vaccine and not the others.

The vaccination site itself is messy and might become infected, and vaccinees are prone to scratch it and then inoculate themselves with the virus. There doubtless will be many phone calls to assure vaccinees that the vaccination site is OK. There also may be satellite lesions and an occasional nasty looking erythema multiforme (see “Which pox is it?”, February issue), but these generally require only reassurance. There is an excellent description of reactions in vaccinees who received varying doses of vaccine to determine whether the available stocks could be diluted and more people immunized (N Engl J Med. 2002;346:1264). More than a third of the patients missed work or school or had difficulty sleeping after receiving the vaccine. In my own experience with children, reactions of this type were uncommon. Of interest is that the vaccinations were covered with porous dressings. What is not mentioned is how these were handled after they were removed. Having hundreds of thousands of these containing live vaccinia out in a community would be a bit scary.

The new recommendations, which are still tentative, can be found at http://www.cdc.gov/nip/smallpox/supp_recs.htm#introduction. They do not recommend routine immunization of physicians. Special facilities would be identified and a team, which would be vaccinated, would be assigned to manage suspected cases. They recommend the development of “response teams” who would investigate possible cases, initiate control measures and facilitate laboratory studies. There is a great chart, which can be copied from the Web site https://www2.cdc.gov/nchstp_od/PIWeb/niporderform.asp. It contains some photos, which you will find very helpful.

An attack is possible

How likely is it that we would have an attack? Unfortunately, it is possible (N Engl J Med. 2002;346(17):1300). There was an effort to restrict smallpox virus to laboratories at CDC and in Russia. However, some countries who were said to have destroyed their smallpox stocks may not have done so, and there is suspicion that some virus may have been smuggled from the Russian stocks and fallen into unfriendly hands.

How would these be used? One scenario is that an infected person could circulate in the community and infect others. Infections require more intimate contact than the childhood exanthems with which we are familiar. If they were dispatched by plane from abroad, the timing of this would be dicey; by the time the victim is able to transmit disease, he or she usually is too sick to be boarding airplanes. Dumping smallpox virus in a ventilation system of a building also might be a method of dissemination. Cases of smallpox in a German hospital were believed to have been spread from an infected patient through the ventilation system infecting people who never had contact with the primary case.

It is important to suspect the diagnosis as vaccination given even a few days after exposure can prevent or modify smallpox. One should know in advance who in your community should be notified if a case is suspected. It also is important to have the response team organized to collect and transport specimens and put isolation procedures in place. Unfortunately, there is no approved treatment, but cidofovir (Vistide Injection, Gilead), which had been tested in animal against related viruses, might be released for treatment of these patients.

There obviously are lots of questions still to be answered. The second-generation tissue culture propagated vaccines which are on the way probably will be safer but would not have been evaluated in clinical trials. How will those who have serious reactions be compensated? One would hope that the recovery from our country’s economic crisis would not be by means of enhancing the income of trial lawyers. The diluted vaccine would be “off label” and probably would have to be treated as an investigational drug. Most physicians in practice have never learned to give smallpox vaccine and have never seen an arm postvaccination. One can expect to see smallpox preparedness appear in many of our requirements for hospital privileges and for hospital accreditation. In any case, be prepared for a lot of discussions with parents.