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Adverse events occurring after smallpox vaccination.

We reviewed the literature on adverse events reported to occur after smallpox vaccination. Nearly one-half of the United States population is vaccinia-naïve and may be at risk for development of serious adverse events. We describe the clinical features of postvaccinial central nervous system disease, progressive vaccinia, eczema vaccinatum, accidental implantations, "generalized vaccinia," and the common erythematous and/or urticarial rashes. In the 1960s, death occurred approximately once in every million primary vaccinations, with fatalities resulting from progressive vaccinia, postvaccinial encephalitis, and eczema vaccinatum. Death in revaccinees occurred less commonly and almost entirely from progressive vaccinia. In today's population, death rates might be higher because of the increased prevalence of immune deficiency and atopic dermatitis.

Encephalomyelitis, Acute Disseminated↗

A postevent smallpox mass vaccination clinic exercise.

Emergency response plans require careful planning and testing. The exercises can be in the form of tabletop, functional, and full-scale activities. To test a regional plan, various agencies from Louisiana, Arkansas, and Texas conducted a postevent mass smallpox vaccination clinic that incorporated federal, state, and local resources. An evaluation of the exercise is provided along with the recommendations for improving a similar future exercise.

Bioterrorism↗

Diagnosis, management, and containment of smallpox infections.

The US public health system and primary health care providers must be prepared to address varied biologic agents, including pathogens that are rarely seen in the United States. The increased frequency of international travel, combined with the current national concerns regarding bioterrorism, create an imperative for health practitioners to be more knowledgeable about specific biologic agents. Smallpox poses a serious bioterrorist threat to the US population at this time. Thus, if an outbreak occurred, prompt recognition and the implementation of control measures would be important.

Bioterrorism↗

Inactivated smallpox vaccine. A comparison of inactivation methods.

Vaccines were prepared from a single pool of high-titred vaccinia virus and inactivated by six methods, namely heat, formalin, hydroxylamine, beta-propiolactone, ultraviolet irradiation, and visible light and methylene blue. Large doses of the vaccines were required to protect mice against intracerebral challenge. Differences in protection were not attributable to the method of their inactivation. The vaccines also induced similar degrees of skin immunity in rabbits which showed no severe dermal reactions when challenged with either homologous killed vaccine or live virus. The virus-neutralizing, haemagglutinin-inhibiting and complement fixing antibody responses to the vaccines differed; heat-inactivation preserved these antigens least well and beta-propiolactone apparently the best. In both rabbits and mice there was little association between the different antibody responses to each vaccine or between the degrees of antibody response and the protection they induced. The relation of these findings to pox-virus immunity and the use of inactivated smallpox vaccine in man is discussed.

Animals↗

Infectiousness of smallpox relative to disease age: estimates based on transmission network and incubation period.

This study investigated the infectiousness of smallpox relative to the onset of fever using a likelihood-based estimation procedure based on the observed transmission network (n=223) and on the distribution of the incubation period (n=379). Who-infected-whom information enabled us to back-calculate the infectiousness by disease age, employing a step function model for infectiousness. Frequency of secondary transmissions was highest between 3 and 6 days after onset of fever, yielding an expected daily frequency of 20.6% (95% CI 15.1-26.4) of the total number of secondary transmissions, which is consistent with previous observations. The estimated cumulative frequency suggests that 91.1% of secondary transmissions occurred up to 9 days after onset of fever. The proposed method appeared to be useful for diseases with an acute course of illness, where transmission was not hampered by depletion of susceptible contacts.

Acute Disease↗

Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room.

Bioterrorism has become a potential diagnostic consideration in infectious diseases. This article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting. The characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed. Ebola vieus and smallpox are also discussed as potential bioterrorist-transmitted infections from the clinical and epidemiologic standpoint. In addition to the clinical features of the infectious diseases mentioned, the article discusses the infectious disease control and epidemiologic implications of these agents when employed as bioterrorist agents. The review concludes with suggestions for postexposure prophylaxis and therapy.

Anthrax↗

Group interest versus self-interest in smallpox vaccination policy.

The recent threat of bioterrorism has fueled debate on smallpox vaccination policy for the United States. Certain policy proposals call for voluntary mass vaccination; however, if individuals decide whether to vaccinate according to self-interest, the level of herd immunity achieved may differ from what is best for the population as a whole. We present a synthesis of game theory and epidemic modeling that formalizes this conflict between self-interest and group interest and shows that voluntary vaccination is unlikely to reach the group-optimal level. This shortfall results in a substantial increase in expected mortality after an attack.

Game Theory↗

Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele.

The high frequency, recent origin, and geographic distribution of the CCR5-Delta 32 deletion allele together indicate that it has been intensely selected in Europe. Although the allele confers resistance against HIV-1, HIV has not existed in the human population long enough to account for this selective pressure. The prevailing hypothesis is that the selective rise of CCR5-Delta 32 to its current frequency can be attributed to bubonic plague. By using a population genetic framework that takes into account the temporal pattern and age-dependent nature of specific diseases, we find that smallpox is more consistent with this historical role.

Adolescent↗

Smallpox vaccination and the patient with an organ transplant.

Organ transplant recipients are vulnerable to a variety of infections because of the immunosuppressed state required to prevent organ rejection. We review the recommendations of the Centers for Disease Control and Prevention (Atlanta, Georgia) for smallpox vaccination and the possible complications of vaccination in the population with organ transplants. The risk of these complications is presumably dependent on the extent of deficient cell-mediated immunity.

Centers for Disease Control and Prevention, U.S.↗

Myocarditis after smallpox vaccination: a case report.

A 20-year-old airman (US Air Force) developed myocarditis 8 days after smallpox vaccination. He was treated with nonsteroidal anti-inflammatory agents, and his symptoms promptly resolved. However, postvaccinial myocarditis can lead to serious complications and even death.

Adult↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Basic study and laboratory standardization.

The present four-center collaborative study was undertaken in an attempt to define the best vaccine and/or vaccination procedure for use in areas of the world that are free of smallpox. The study was designed to compare the effect of different vaccinial strains, viral concentrations, and routes of administration on the morbidity and antibody response associated with primary vaccination and standard challenge revaccination. Primary vaccinations were performed on 1,585 children; 49.6% of the children were vaccinated by the percutaneous route, and 50.4% received vaccine subcutaneously. The overall age and sex distributions of percutaneous and subcutaneous vaccinees were comparable, but there were marked differences in participants among the four study centers. Vaccines in Kentucky had a greater mean age; the greatest number of Negroid children were enrolled in St. Louis, and more of them were vaccinated by the subcutaneous route; and the dropout rate was much greater in San Diego and Colorado. An analysis of comparative interlaboratory serologic procedures with the use of 20 coded duplicate samples of serum revealed good agreement in the hemagglutination-inhibition test; results of neutralization tests had greater variability of mean titers. On duplicate samples of serum from study participants there was generally good correlation between each of the four study centers and the Center for Disease Control's reference laboratory in titers of hemagglutination-inhibiting antibody. In contrast, 38% of the neutralization titers determined at the four study centers were greater than or equal to 0.67 log10 higher than the respective titers noted at the Center for Disease Control.

Black or African American↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary percutaneous vaccination.

In an investigation of the antigenicity and reactogenicity of four smallpox vaccines, 786 children received primary percutaneous vaccination with vaccine in one of three concentrations, 10(6), 10(7), or10(8) pock-forming units/ml. Dose-response curves indicated that the three licensed vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membrane, and the Lister vaccine) had similar potencies, but the CV-1 strain was about 10-fold less infectious. CV-1 also produced smaller skin lesions than the other three vaccines, and the incidence of fever in CV-1 vaccines who developed either "major reactions" or serum antibody was not significantly different from that in children in all vaccine groups with no evidence of "take." Hemmagglutination-inhibiting antibody was consistently seen in individuals who received potent New York City and Lister vaccines, and neutralizing antibody was induced in 82%-85% of children in this group who had some evidence of take (production of hemagglutination-inhibiting antibody or or major reaction). Only 30% of CV-1 vaccines with takes produced neutralizing antibody. Minor complications occurred in all groups, but most often in children who received the New York City strains."

Animals↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination.

A standard challenge with percutaneous smallpox vaccine was administered to 629 children six to 12 months after percutaneous primary inoculation with one of four vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membranes, the Lister vaccine, or the CV-1 strain). Of those who had had major reactions on primary vaccination, 8%-21% responded to revasccination with a typical primary-type skin response. In contrast, such a primary-type response occurred in 50% of those who on primary vaccination had developed serum antibody in the absence of major reactions and in 83% of those who had had no serologic or clinical evidence of primary "take." Skin lesions on revaccination tended to be largest in thosewhose primary vaccination was with CV-1, although fever and minor complications were not more frequent. Moreover, even in children who had received CV-1 vaccine, skin responses to challenge vaccine were clearly attenuated when compared with responses of children who had not had takes on primary vaccination. Sizes of lesions and acceleration of skin erytherma after challenge were related in most children to titers of both hemagglutination-inhibiting and neutralizing antibody at the time of revaccination. One month after revaccination, neutralizing antibody was present in 93%-96% of those with takes onprimary vaccination with New York City or Lister vaccines, but only 75% of CV-1 vaccines.

Antibody Formation↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary subcutaneous vaccination.

As part of a large study designed to develop schedules for smallpox immunization with reduced morbidity, 799 children received primary immunization with subcutaneous vaccine. Four vaccines (New York City Board of Health calf lymph, New York City chorioallantoic membrane, CV-1 and Lister) at three dosages (l0(3), 10(4), 10(5) pock-forming units) were administered. Eighty-two percent responded with hemagglutination-inhibiting antibody at one month, and only 22% with neutralizing antibody. There was no correlation between concentration of vaccine and antibody response. The CV-1 strain was slightly but significantly less likely to induce antibody than the other three vaccines. Subcutaneous vaccination was not associated with significant temperature elevation in general. However, some children developed erythema at the vaccination site or a swollen arm, and fever did tend to occur in this small group. Four children developed nonspecific vaccinia-related rashes, and one had generalized vaccinia.

Antibody Formation↗

Vaccinia necrosum after smallpox vaccination for herpes labialis.

We have described a patient with vaccinia necrosum after smallpox vaccination for persistent herpes labialis. The patient eventually recovered after surgical resection of the lesion and multiple courses of vaccinia immune globulin and methisazone. This report emphasizes the needless risks of vaccinating patients with herpetic infections.

Female↗

New Jersey's smallpox vaccination clinic experiences, 2003.

PURPOSE: During 2003, the New Jersey Department of Health and Senior Services, in collaboration with other agencies, began planning and implementing voluntary smallpox vaccination clinics. METHODS: Surveys were distributed to all vaccinees, hospital bioterrorism coordinators, and local health departments to assess clinic experiences. RESULTS: During January-July 2003, 23 clinics were conducted with more than 1,000 participants. Of 670 persons vaccinated, 529 (79%) completed surveys. We received 65 surveys from 68 (77%) of 84 hospitals, and 25 responses from 22 regional health agencies. CONCLUSIONS: Vaccination is one component of preparedness; future initiatives must incorporate multiagency collaboration and developing public health infrastructure.

Bioterrorism↗