Laboratory-Acquired Vaccinia Exposures and Infections --- United States, 2005--2007
The last case of naturally acquired smallpox disease, caused by the orthopoxvirus variola virus (VARV), occurred in 1977, and the last laboratory-acquired case occurred in 1978. Smallpox was eradicated largely as the result of a worldwide vaccination campaign that used the related orthopoxvirus, vaccinia virus (VACV), as a live virus vaccine. Routine childhood vaccination for smallpox in the United States was terminated by 1972, but vaccination continues or has been reintroduced for specific groups, including laboratory workers who may be exposed to orthopoxviruses, members of the military, selected health-care workers, and first responders. Severe complications of VACV infection can occur, particularly in persons with underlying risk factors, and secondary transmission of VACV also can occur (1). VACV is used in numerous institutions for various research purposes, including fundamental studies of orthopoxviruses and use as a vector for the expression of foreign proteins (often antigens or immunomodulators) in eukaryotic cells and animal models. The widespread use of VACV for research has resulted in laboratory-acquired VACV infections, some requiring hospitalization. The current Advisory Committee on Immunization Practices (ACIP) guidelines recommend VACV vaccination for laboratory workers who handle cultures or animals contaminated or infected with nonhighly attenuated VACV strains or other orthopoxviruses that infect humans (2). This report describes five recent occurrences of laboratory-acquired VACV infections and exposure and underscores the need for proper vaccination, laboratory safety, infection-control practices, and rapid medical evaluation of exposures in the context of orthopoxvirus research.
During 2005--2007, five cases of laboratory-acquired VACV infection were reported to CDC from state health departments and health-care providers in the United States. No national surveillance system exists to track laboratory-related VACV exposures, and the five cases were reported to CDC informally in the course of seeking consultation on treatment and prevention. All five cases involved the Western Reserve (WR) vaccinia strain. Cases 1--4 involved recombinant VACVs with an insertion at the thymidine kinase (TK) locus. Case 5 also involved a recombinant VACV, but details of the virus are not known (Table).
Case 1. In March 2005, a laboratory worker at an academic institution in Connecticut experienced a needlestick to a finger while injecting mice with recombinant VACV. The laboratory worker was admitted to a hospital 3 days later with fever, lymphadenopathy, lymphangitis, and a hemorrhagic bulla at the site of the injury. The laboratory worker had been vaccinated with VACV as a child, and a second time approximately 10 years before the incident. Symptoms improved rapidly, and the laboratory worker was released after one night in the hospital. Infection with an orthopoxvirus was confirmed by testing in the state's Laboratory Response Network (LRN) laboratory.
Case 2. In October 2006, a laboratory worker at an academic institution in Pennsylvania experienced a needlestick injury on the thumb while injecting a mouse with a recombinant WR VACV strain. The laboratory worker had previously declined VACV vaccination. Six days after the incident, the laboratory worker sought medical care, with a primary lesion at the site of the inoculation and a secondary lesion near the thumbnail. Nine days after inoculation, the laboratory worker reported malaise, and on the following day, had a fever of 102.0°F (38.9°C) and lymphadenopathy. By day 13, the laboratory worker was feeling better; on day 14, a surgeon debrided the lesion near the thumbnail. VACV infection was confirmed by polymerase chain reaction and viral culture at CDC.
Case 3. In May 2007, a laboratory worker at an academic institution in Iowa who had no previous history of VACV vaccination was unsheathing a sterile needle and received a needlestick in a finger. The laboratory worker continued with the experiments, which involved two recombinant VACVs, and did not change gloves or wash hands until finished. The typical challenge dose for this set of experiments was 3 ´ 106 plaque-forming units (pfu). Approximately 11 days after the needlestick, the laboratory worker developed symptoms of VACV infection, including fever and chills, and noted a lesion and swelling at the site of the needlestick. The laboratory worker sought medical attention at an urgent-care facility and informed the clinical staff of the incident. A diagnosis of VACV infection was confirmed by the state LRN laboratory. The laboratory worker recovered fully.
Case 4. In August 2007, a laboratory worker at a government facility in Maryland unintentionally inoculated a finger with approximately 5 µL of a solution containing VACV, after injection of a research animal. The inoculum contained up to 104 pfu of the virus, which was a recombinant strain of WR VACV. The laboratory worker did not wash the exposed area immediately, but instead immersed the wound in a disinfectant containing hypochlorite for a few minutes. The laboratory worker had received a primary VACV vaccination in 2001, but immunization was unsuccessful (i.e., no lesion developed at the site of the vaccination). On the day of the incident, the laboratory worker went to the occupational health clinic and was revaccinated with VACV. Vaccinia immunoglobulin was not administered. When the worker was reevaluated on days 3, 4, and 5 postvaccination, no evidence of VACV infection was observed at the site of inoculation, and a characteristic lesion developed at the site of vaccination, evidence of a take.
Case 5. In September 2007, a laboratory worker at an academic institution in New Hampshire who had no history of vaccination incurred a minor scratch to a finger with a small-gauge needle containing 5 ´ 104 pfu/mL of recombinant WR VACV, which was being used for injecting mice. The laboratory worker felt pain, but did not bleed, and so continued working. Seven days later, the laboratory worker noted a pustule at the site of the scratch, sought medical attention the following day, and was hospitalized when red streaking appeared from the site of the scratch and extended into the axilla. Samples from the pustule were submitted to the state LRN laboratory, where VACV infection was confirmed. The laboratory worker was afebrile and recovered without specific therapy.
Reported by: R Melchreit, MD, Connecticut Dept of Public Health. F Lewis, MD, Philadelphia Dept of Public Health, Pennsylvania. P Quinlisk, MD, K Soyemi, MD, Iowa Dept of Public Health; L DesJardin, PhD, Univ of Iowa Hygienic Laboratory; LV Kirchhoff, MD, Univ of Iowa. EA Talbot, MD, Dartmouth Medical School; C Bean, PhD, New Hampshire Dept of Health and Human Svcs. J Schmitt, MD, National Institutes of Health. M Reynolds, PhD, W Davidson, MPH, S Smith, MS, Y Li, PhD, I Damon, MD, PhD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; A MacNeil, PhD, D Dufficy, DVM, EIS officers, CDC.
Although laboratory-related VACV exposures are rare, the cases described in this report demonstrate the need for laboratory workers to comply with ACIP vaccination recommendations (3,4). The total number of laboratories or researchers using nonhighly attenuated-VACV strains is unknown; therefore, estimating the incidence of VACV infection among at-risk laboratory workers is not possible. However, CDC does continue to receive reports of laboratory-related VACV exposures (fewer than five per year).
Laboratory-acquired exposure to VACV can lead to severe or atypical infections; exposures can be associated with a high inoculum or can occur through a route that has a high risk of complications, such as ocular VACV infection (5). Recombinant strains of VACV are commonly generated by insertion of genetic material in the TK locus of the virus. Because inactivation of the TK locus has been associated with decreased VACV virulence in mice (6), some laboratory workers might perceive TK insertion mutants as attenuated; however, at least four of the infections and attendant illnesses described in this report involved VACV strains that had insertions at the TK locus. Additionally, recombinant strains of VACV commonly encode foreign gene products, and the possibility exists that resultant recombinant strains might have increased pathogenicity in humans.
ACIP currently recommends VACV vaccination at least every 10 years for laboratory workers who handle cultures or animals infected with nonhighly attenuated orthopoxviruses (2), including the WR strain of VACV. Reasons the five persons described in this report failed to meet ACIP recommendations included refusal of vaccination, absence of follow-through on a failed vaccination take, and overdue revaccination. Because some laboratory workers are hesitant to receive VACV vaccination for fear of side effects, laboratory directors and occupational health programs are encouraged to provide education regarding the risks and potential benefits of vaccination, including, for the latter, the prevention or reduction of severe complications from laboratory-acquired VACV infection. This benefit accrues from receiving a carefully measured (rather than undetermined) dose of a well-characterized vaccine formulation, which results in local infection at a predetermined site on the body, and resultant memory-immune response on subsequent exposure. Laboratory workers should adhere to the vaccination schedule recommended by ACIP (2). Persons who have a contraindication to VACV vaccination should consider carefully the possible consequences of a laboratory-acquired VACV infection in their decisions to work with nonhighly attenuated VACV.
Laboratory directors, research staff, and institutional biosafety officials can further minimize the likelihood of inadvertent VACV exposure by reinforcing proper laboratory safety procedures, such as proper use of personal protective equipment and safe needle-handling practices when handling VACV-infected cultures or animals.
When a potential exposure occurs, the laboratory worker should immediately and thoroughly wash the affected body part with water and the available cleaning product sanctioned by their biosafety office; eyewash protocols should be followed for ocular exposures. The laboratory worker should then report the incident and strain to which they might have been exposed to the laboratory director and the occupational health clinic of the institution. VACV vaccination shortly after an exposure might help minimize the effects of inadvertent VACV infection. If severe illness or ocular infection occur, arrangements can be made with CDC for the administration of vaccinia immunoglobulin (2,3). The laboratory worker in case 4 immediately disinfected the wound and received prompt postexposure vaccination the day of the laboratory incident; this might have contributed to preventing infection at the site of the needlestick.
Secondary spread of VACV represents an additional public health concern. Patients with suspected VACV infection should be instructed by their caregivers in appropriate lesion care (2) as a precaution against spread of infection to another body site or to another person. Special care must be taken to avoid transmission to social contacts and persons in the health-care setting, particularly those with increased risk for severe illness from exposure to VACV, such as persons with atopic dermatitis, pregnant females, and immunocompromised persons.
Finally, occupational health clinics and health-care workers who might provide primary care for a laboratory worker exposed to VACV should become familiar with protocols for recognition and diagnosis of suspected poxvirus infections (3). Laboratory workers also should be instructed to seek care from appropriately trained health-care providers at their supporting institution. Appropriate infection-control measures should be instituted at the time of presentation of a patient with a suspected case, and whenever possible, clinical care should be provided by persons who have been vaccinated with VACV. Clinics also should review procedures for communication with and confirmation of orthopoxvirus infection through the LRN or the Poxvirus Program (404-639-4129) at CDC.
- CDC. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions. MMWR 2006;55(No. RR-1).
- CDC. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR 2001;50(No. RR-10).
- CDC. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR 2003;52(No. RR-4).
- CDC. Recommendations for using smallpox vaccine in a pre-event vaccination program. MMWR 2003;52(No. RR-7).
- Lewis FM, Chernak E, Goldman E, et al. Ocular vaccinia infection in laboratory worker, Philadelphia, 2004. Emerg Infect Dis 2006;12: 134--7.
- Lee MS, Roos JM, McGuigan LC, et al. Molecular attenuation of vaccinia virus: mutant generation and animal characterization. J Virol 1992;66:2617--30.
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Date last reviewed: 4/16/2008
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