Dermatological lesions near the smallpox vaccination site after scab detachment.

Lesions arising after scab detachment at the smallpox vaccination site have been described in the medical literature. We investigated reports of postscab lesions among US civilian volunteers vaccinated against smallpox from January through August 2003. We conducted enhanced surveillance, using a standard questionnaire, for reports of skin lesions appearing at or near the smallpox vaccination site after scab detachment. We identified 21 reports; 19 of the case patients responded to our questionnaire. The lesions (scab and/or fluid) of 7 case patients were tested for vaccinia virus by use of polymerase chain reaction and/or immunohistochemistry; all were found to be negative. We contacted 18 case patients 11 months after the initial lesion appearance; 10 (56%) of the 18 reported having another lesion appear after the initial postscab lesion had resolved. Lesions were heterogeneous in morphology, clinical appearance, and histology. The evidence from our case series and follow-up suggests that these lesions are self-limited, without significant clinical sequelae.

Myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination among civilians in the United States, January-October 2003.

Myocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians.

Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and corticosteroid therapy: eleven United States cases, 1996-2004.

During 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal. Stress-dose corticosteroid (SDS) therapy has recently been found to improve survival among patients with septic shock but benefit for the treatment of YEL-AVD patients in septic shock is unknown. We retrospectively reviewed medical records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3 of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%) survived. Altered mental status was documented on admission for 5 of the 11 patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and survived. The use of stress-dose steroids might be a factor that influenced the survival of these YEL-AVD patients and should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.

Active telephone surveillance to evaluate adverse events among civilian smallpox vaccine recipients.

OBJECTIVE: Better characterize and monitor adverse events following Dryvax vaccinia vaccination in civilian health care workers and other first responders. DESIGN: Telephone interviews to ascertain adverse events experienced. RESULTS: Eight hundred twenty-five vaccinees, including 44 in the comparison group, were interviewed. At 10 days, 71.4% reported blisters, 35.1% reported bumps at the vaccination site, 48.5% swelling, 47.3% scab, tiredness/lethargy/fatigue (43.6%), headache (34.2%), lymph node swelling/tenderness (28.5%), muscle pain (23.1%), chills (14.4%), joint pain 11.8%, and fever >100 degrees F (12.5%). The 12.5% reported missing work because of vaccine adverse events. Most adverse events were anticipated and of short duration.

Adverse events associated with smallpox vaccination in the United States, January-October 2003.

CONTEXT: On January 24, 2003, the US Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a bioterrorism event. OBJECTIVE: To describe results from the comprehensive DHHS smallpox vaccine safety monitoring and response system. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of adverse event reports from the DHHS smallpox vaccine safety monitoring and response system received between January 24 and October 31, 2003, through the Vaccine Adverse Event Reporting System (VAERS) and the Centers for Disease Control and Prevention. A total of 37,901 volunteers in 55 jurisdictions received at least 1 dose of smallpox vaccine. MAIN OUTCOME MEASURES: Number of vaccinations administered and description of adverse events and reporting rates. RESULTS: A total of 38,885 smallpox vaccinations were administered, with a take rate of 92%. VAERS received 822 reports of adverse events following smallpox vaccination (overall reporting rate, 217 per 10,000 vaccinees). A total of 590 adverse events (72%) were reported within 14 days of vaccination. Nonserious adverse events (n = 722) included multiple signs and symptoms of mild and self-limited local reactions. One hundred adverse events (12%) were designated as serious, resulting in 85 hospitalizations, 2 permanent disabilities, 10 life-threatening illnesses, and 3 deaths. Among the serious adverse events, 21 cases were classified as myocarditis and/or pericarditis and 10 as ischemic cardiac events that were not anticipated based on historical data. Two cases of generalized vaccinia and 1 case of postvaccinial encephalitis were detected. No preventable life-threatening adverse reactions, contact transmissions, or adverse reactions that required treatment with vaccinia immune globulin were identified. Serious adverse events were more common among older revaccinees than younger first-time vaccinees. CONCLUSIONS: Rigorous smallpox vaccine safety screening, educational programs, and older vaccinees may have contributed to low rates of preventable life-threatening adverse reactions. Other rare, clinically significant, or unexpected cardiac adverse events were detected by timely review of VAERS data and intensive clinical case investigation.

Superinfection following smallpox vaccination (Vaccinia), United States: surveillance January 2003 through January 2004.

BACKGROUND: Superinfection is an adverse event following smallpox vaccination. The clinical presentation is similar to that of a large normal vaccine reaction or "robust take," and the frequency is unknown. METHODS: We retrospectively reviewed all reported severe local reactions consistent with superinfection among United States civilian smallpox vaccinees from January 2003 through January 2004. We applied a standard case definition and estimated the frequency of superinfection following smallpox vaccination. RESULTS: We identified 48 reported cases for further review among 39,350 [corrected] smallpox vaccinees. Two (4%) of the 48 reported cases met the case definition for superinfection; neither of the patients had a pathogenic organism isolated from their infection site. Both were treated with antibiotics and resolved their infection. Of the 46 cases determined not to be superinfection, 41 (89%) were temporally consistent with a large normal vaccine reaction. Thirty (75%) of 40 reported case patients for whom data were available received antibiotic therapy. CONCLUSIONS: Superinfection following smallpox vaccination is rare. Most of the reported superinfection cases were probably large normal smallpox vaccine reactions. Educating providers about the normal response to smallpox vaccine may decrease the overdiagnosis of superinfection and the unnecessary use of antimicrobials.

Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC).

This report supplements the 2001 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. Vaccinia [smallpox] vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP], 2001. MMWR 2001;50[No. RR-10]:1-25). This supplemental report provides recommendations for using smallpox vaccine in the pre-event vaccination program in the United States. To facilitate preparedness and response, smallpox vaccination is recommended for persons designated by public health authorities to conduct investigation and follow-up of initial smallpox cases that might necessitate direct patient contact. ACIP recommends that each state and territory establish and maintain > or = 1 smallpox response team. ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that each acute-care hospital identify health-care workers who can be vaccinated and trained to provide direct medical care for the first smallpox patients requiring hospital admission and to evaluate and manage patients who are suspected as having smallpox. When feasible, the first-stage vaccination program should include previously vaccinated health-care personnel to decrease the potential for adverse events. Additionally persons administering smallpox vaccine in this pre-event vaccination program should be vaccinated. Smallpox vaccine is administered by using the multiple-puncture technique with a bifurcated needle, packaged with the vaccine and diluent. According to the product labeling, 2-3 punctures are recommended for primary vaccination and 15 punctures for revaccination. A trace of blood should appear at the vaccination site after 15-20 seconds; if no trace of blood is visible, an additional 3 insertions should be made by using the same bifurcated needle without reinserting the needle into the vaccine vial. If no evidence of vaccine take is apparent after 7 days, the person can be vaccinated again. Optimal infection-control practices and appropriate site care should prevent transmission of vaccinia virus from vaccinated health-care workers to patients. Health-care personnel providing direct patient care should keep their vaccination sites covered with gauze in combination with a semipermeable membrane dressing to absorb exudates and to provide a barrier for containment of vaccinia virus to minimize the risk of transmission; the dressing should also be covered by a layer of clothing. Dressings used to cover the site should be changed frequently to prevent accumulation of exudates and consequent maceration. The most critical measure in preventing contact transmission is consistent hand hygiene. Hospitals should designate staff to assess dressings for all vaccinated health-care workers. When feasible, staff responsible for dressing changes for smallpox health-care teams should be vaccinated, all persons handling dressings should observe contact precautions. Administrative leave is not required routinely for newly vaccinated health-care personnel unless they are physically unable to work as a result of systemic signs and symptoms of illness; have extensive skin lesions that cannot be adequately covered or if they are unable to adhere to the recommended infection-control precautions. Persons outside the patient-care setting can keep their vaccination sites covered with a porous dressing hand hygiene remains key to preventing inadvertent inoculation. FDA has recommended that recipients of smallpox vaccine be deferred from donating blood for 21 days or until the scab has separated. Contacts of vaccinees, who have inadvertently contracted vaccinia, also should be deferred from donating blood for 14 days after complete resolution of their complication. In the pre-event vaccination program, smallpox vaccination is contraindicated for persons with a history or presence of eczema or atopic dermatitis; who have other acute, chronic, or exfoliative skin conditions; who have conditions associated with immunosuppression; are aged < 1 year; who have a serious allergy to any component of the vaccine; or who are pregnant or breastfeeding. ACIP does not recommend smallpox vaccination for children and adolescents aged < 18 years during the pre-event vaccination program. Pre-event vaccination also is contraindicated among persons with household contacts who have a history or presence of eczema or atopic dermatitis; who have other acute, chronic, or exfoliative skin conditions; who have conditions associated with immunosuppression; or who are pregnant. For purposes of screening for contraindications for pre-event vaccination, household contacts include persons with prolonged intimate contact (e.g., sexual contacts) with the potential vaccinee and others who might have direct contact with the vaccination site. Persons with inflammatory eye disease might be at increased risk for inadvertent inoculation as a result of touching or rubbing the eye. Therefore, deferring vaccination is prudent for persons with inflammatory eye diseases requiring steroid treatment until the condition resolves and the course of therapy is complete. Eczema vaccinatum, a serious form of disseminated vaccinia infection, can occur among persons with atopic dermatitis and other dermatologic conditions. Potential vaccinees should be queried regarding the diagnosis of atopic dermatitis or eczema in themselves or any member of their household, or regarding the presence of chronic or recurrent rashes consistent with these diagnoses. Persons reporting such a rash in themselves or household members should not be vaccinated, unless a health-care provider determines that the rash is not eczema or atopic dermatitis. Before vaccination, women of childbearing age should be asked if they are pregnant or intend to become pregnant during the next 4 weeks; women who respond positively should not be vaccinated. Any woman who thinks she might be pregnant or who wants additional assurance that she is not pregnant should perform a urine pregnancy test on the day scheduled for vaccination. If a pregnant woman is inadvertently vaccinated or if she becomes pregnant within 4 weeks after smallpox vaccination, she should be counseled regarding concerns for the fetus. Vaccination during pregnancy should not ordinarily be a reason to terminate pregnancy. CDC has established a pregnancy registry to prospectively follow the outcome of such pregnancies and facilitate the investigation of any adverse pregnancy outcome among pregnant women who were inadvertently vaccinated. For enrollment in the registry, contact CDC at 404-639-8253. Smallpox vaccine should not be administered to persons with human immunodeficiency virus infection (HIV) or acquired immunodeficiency syndrome (AIDS) as part of a pre-event program because of their increased risk for progressive vaccinia. HIV testing is recommended for persons who have any history of a risk factor for HIV infection or for anyone who is concerned that he or she might have HIV infection. HIV testing should be available in a confidential or anonymous setting, in accordance with local laws and regulations, with results communicated to the potential vaccinee before the planned date of vaccination. Smallpox vaccine can be administered simultaneously with any inactivated vaccine. With the exception of varicella vaccine, smallpox vaccine can be administered simultaneously with other live-virus vaccines. To avoid confusion in ascertaining which vaccine might have caused postvaccination skin lesions or other adverse events, varicella vaccine and smallpox vaccine should be administered >4 weeks apart. Health-care workers scheduled to receive an annual purified protein derivative (PPD) skin test for tuberculosis screening should not receive the skin test until >1 month after smallpox vaccination. Persons with progressive vaccinia, eczema vaccinatum, and severe generalized vaccinia or inadvertent inoculation might benefit from therapy with VIG or cidofovir, although the latter has not been approved by FDA for this indication. Suspected cases of these illnesses or other severe adverse events after smallpox vaccination should be reported immediately to state health departments. VIG and cidofovir are available from CDC under Investigational New Drug protocols. Clinically severe adverse events after smallpox vaccination should be reported to the Vaccine Adverse Event Reporting System. Reports can be made online at https://secure.vaers.org/VaersDataEntryintro.htm, or by postage-paid form, which is available by calling 800-822-7967 (toll-free). ACIP will review these recommendations periodically as new information becomes available related to smallpox disease, smallpox vaccines, the risk of smallpox attack, smallpox vaccine adverse events, and the experience gained as recent recommendations are implemented. Revised recommendations will be developed as needed.

Smallpox vaccination and adverse reactions. Guidance for clinicians.

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.