Excerpt: Vaccinia (Smallpox) Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001


These revised recommendations regarding vaccinia (smallpox) vaccine update the previous Advisory Committee on Immunization Practices (ACIP) recommendations (MMWR 1991; 40; No. RR-14:1-10) and include current information regarding the nonemergency use of vaccinia vaccine among laboratory and health care workers occupationally exposed to vaccinia virus, recombinant vaccinia viruses, and other Orthopoxviruses that can infect humans. In addition, this report contains ACIP’s recommendations for the use of vaccinia vaccine if smallpox (variola) virus were used as an agent of biological terrorism or if a smallpox outbreak were to occur for another unforeseen reason.


Variola virus is the etiological agent of smallpox. During the smallpox era, the only known reservoir for the virus was humans; no known animal or insect reservoirs or vectors existed. The most frequent mode of transmission was person-to-person, spread through direct deposit of infective droplets onto the nasal, oral, or pharyngeal mucosal membranes, or the alveoli of the lungs from close, face-to-face contact with an infectious person. Indirect spread (i.e., not requiring face-to-face contact with an infectious person) through fine-particle aerosols or a fomite containing the virus was less common.

Symptoms of smallpox begin 12-14 days (range: 7-17) after exposure, starting with a two- to three-day prodrome of high fever, malaise, and prostration with severe headache and backache. This pre-eruptive stage is followed by the appearance of a maculopapular rash (i.e., eruptive stage) that progresses to papules one to two days after the rash appears; vesicles appear on the fourth or fifth day; pustules appear by the seventh day; and scab lesions appear on the 14th day. The rash appears first on the oral mucosa, face, and forearms, then spreads to the trunk and legs. Lesions might erupt on the palms and soles as well. Smallpox skin lesions are deeply embedded in the dermis and feel like firm round objects embedded in the skin. As the skin lesions heal, the scabs separate and pitted scarring gradually develops. Smallpox patients are most infectious during the first week of the rash when the oral mucosa lesions ulcerate and release substantial amounts of virus into the saliva. A patient is no longer infectious after all scabs have separated (i.e., three to four weeks after the onset of the rash).

During the smallpox era, overall mortality rates were approximately 30%. Other less common but more severe forms of smallpox included: a) flat-type smallpox with a mortality rate >96% and characterized by severe toxemia and flat, velvety, confluent lesions that did not progress to the pustular stage; and b) hemorrhagic-type smallpox, characterized by severe prodromal symptoms, toxemia, and a hemorrhagic rash that was almost always fatal, with death occurring 5-6 days after rash onset.

Vaccinia vaccine is a highly effective immunizing agent that enabled the global eradication of smallpox. The last naturally occurring case of smallpox occurred in Somalia in 1977. In May 1980, the World Health Assembly certified that the world was free of naturally occurring smallpox. By the 1960s, because of vaccination programs and quarantine regulations, the risk for importation of smallpox into the United States had been reduced. As a result, recommendations for routine smallpox vaccination were rescinded in 1971. In 1976, the recommendation for routine smallpox vaccination of health care workers also was discontinued. In 1982, the only active licensed producer of vaccinia vaccine in the United States discontinued production for general use, and in 1983, distribution to the civilian population was discontinued. All military personnel continued to be vaccinated, but that practice ceased in 1990. Since January 1982, smallpox vaccination has not been required for international travelers, and International Certificates of Vaccination forms no longer include a space to record smallpox vaccination.

Currently, international concern is heightened regarding the potential use of smallpox (variola) virus as a bioterrorism agent. Because of these concerns, ACIP has developed recommendations for vaccinia (smallpox) vaccine regarding the potential use of smallpox virus as a biological weapon. Additionally, recommendations regarding vaccination of persons working with highly attenuated strains or recombinant vaccines derived from highly attenuated strains of vaccinia virus have been revised.


Although use of biological agents is an increasing threat, use of conventional weapons (e.g., explosives) still is considered more likely in terrorism scenarios. Moreover, use of smallpox virus as a biological weapon might be less likely than other biological agents because of its restricted availability; however, its use would have substantial public health consequences. Therefore, in support of current public health bioterrorism preparedness efforts, ACIP has developed the following recommendations if this unlikely event occurs.


A suspected case of smallpox is a public health emergency. Smallpox surveillance in the United States includes detecting a suspected case or cases, making a definitive diagnosis with rapid laboratory confirmation at CDC, and preventing further smallpox transmission. A suspected smallpox case should be reported immediately by telephone to state or local health officials and advice obtained regarding isolation and laboratory specimen collection. State or local health officials should notify CDC immediately at (404) 639-2184, (404) 639-0385, or (770) 488-7100 if a suspected case of smallpox is reported. Because of the problems previously encountered in Europe with health care-associated smallpox transmission from imported cases present in a hospital setting, health officials should be diligent regarding use of adequate isolation facilities and precautions (see Infection Control Measures). Currently, specific therapies with proven treatment effectiveness for clinical smallpox are unavailable. Medical care of more seriously ill smallpox patients would include supportive measures only. If the patient’s condition allows, medical and public health authorities should consider isolation and observation outside a hospital setting to prevent health care-associated smallpox transmission and overtaxing of medical resources. Clinical consultation and a preliminary laboratory diagnosis can be completed within eight to 24 hours. Surveillance activities, including notification procedures and laboratory confirmation of cases, might change if smallpox is confirmed.

Prerelease Vaccination

The risk for smallpox occurring as a result of a deliberate release by terrorists is considered low, and the population at risk for such an exposure cannot be determined. Therefore, pre-exposure vaccination is not recommended for any group other than laboratory or medical personnel working with nonhighly attenuated Orthopoxviruses.

Recommendations regarding pre-exposure vaccination should be on the basis of a calculable risk assessment that considers the risk for disease and the benefits and risks regarding vaccination. Because the current risk for exposure is considered low, benefits of vaccination do not outweigh the risk regarding vaccine complications. If the potential for an intentional release of smallpox virus increases later, pre-exposure vaccination might become indicated for selected groups (e.g., medical and public health personnel or laboratorians) who would have an identified higher risk for exposure because of work-related contact with smallpox patients or infectious materials.

Postrelease Vaccination

If an intentional release of smallpox (variola) virus does occur, vaccinia vaccine will be recommended for certain groups. Groups for whom vaccination would be indicated include:

• persons who were exposed to the initial release of the virus;

• persons who had face-to-face, household, or close-proximity contact (<6.5 feet or 2 meters) with a confirmed or suspected smallpox patient at any time from the onset of the patient’s fever until all scabs have separated;

• personnel involved in the direct medical or public health evaluation, care, or transportation of confirmed or suspected smallpox patients;

• laboratory personnel involved in the collection or processing of clinical specimens from confirmed or suspected smallpox patients; and

• other persons who have an increased likelihood of contact with infectious materials from a smallpox patient (e.g., personnel responsible for medical waste disposal, linen disposal or disinfection, and room disinfection in a facility where smallpox patients are present).

Infection Control Measures

Isolation of confirmed or suspected smallpox patients will be necessary to limit the potential exposure of nonvaccinated and, therefore, nonimmune persons. Although droplet spread is the major mode of person-to-person smallpox transmission, airborne transmission through fine-particle aerosol can occur. Therefore, airborne precautions using correct ventilation (e.g., negative air-pressure rooms with high-efficiency particulate air filtration) should be initiated for hospitalized confirmed or suspected smallpox patients, unless the entire facility has been restricted to smallpox patients and recently vaccinated persons. Although personnel who have been recently vaccinated and who have a demonstrated immune response should be fully protected against infection with variola virus, they should continue to observe standard and contact precautions (i.e., using protective clothing and shoe covers) when in contact with smallpox patients or contaminated materials to prevent inadvertent spread of variola virus to susceptible persons and potential self-contact with other infectious agents. Personnel should remove and correctly dispose of all protective clothing before contact with nonvaccinated persons. Reusable bedding and clothing can be autoclaved or laundered in hot water with bleach to inactivate the virus. Laundry handlers should be vaccinated before handling contaminated materials.

Nonhospital isolation of confirmed or suspected smallpox patients should be of a sufficient degree to prevent the spread of disease to nonimmune persons during the time the patient is considered potentially infectious (i.e., from the onset of symptoms until all scabs have separated). Private residences or other nonhospital facilities that are used to isolate confirmed or suspected smallpox patients should have nonshared ventilation, heating, and air-conditioning systems. Access to those facilities should be limited to recently vaccinated persons with a demonstrated immune response. If suspected smallpox patients are placed in the same isolation facility, they should be vaccinated to guard against accidental exposure caused by misclassification as someone with smallpox.

In addition to isolation of infectious smallpox patients, careful surveillance of contacts during their potential incubation period is required. Transmission of smallpox virus rarely occurs before the appearance of the rash that develops two to four days after the prodromal fever. If a vaccinated or unvaccinated contact experiences a fever >101° F (38° C) during the 17-day period after his or her last exposure to a smallpox patient, the contact should be isolated immediately to prevent contact with nonvaccinated or nonimmune persons until smallpox can be ruled out by clinical or laboratory examination.

Source: Centers for Disease Control and Prevention, Atlanta.