A lab worker sustained a needlestick exposure to the Vaccinia virus (VACV) — an Orthopoxvirus used in biomedical research — and was removed from work for four months, the CDC reported.1

In December 2018, a healthy, 26-year-old female laboratorian was injecting VACV into the tail of a mouse when she sustained a needlestick injury to her left index finger. The lab worker rinsed the wound with water and was advised by a supervisor to visit the local ED. A few months earlier, the lab worker was advised of the risks of working with VACV, but declined immunization with the ACAM2000 vaccine.

“Between days two and nine post-infection, the patient was evaluated by two community physicians; neither advised her to observe contact precautions to prevent autoinoculation or secondary transmission,” the CDC reported. Despite this lapse, the VACV did not spread from the wound site to others, and the patient did not self-inoculate by, for example, touching her eyes.

Ten days after the needlestick, she presented at occupational health clinic with swelling and a vesicular lesion at the injury site. The treating physician contacted CDC and the San Diego Health Department, which advised monitoring her for evidence of worsening infection.

“On day 12, she was treated at a university-based emergency department for fever, left axillary lymphadenopathy, malaise, pain, and worsening edema of her finger,” the CDC reported. “Healthcare providers were concerned about progression to compartment syndrome, joint infection, or further spread.”

Complicating the situation, the specific VACV strain could not be determined. Thus, the severity and progress of the infection could not be predicted. The patient received a single 6,000 IU/kg dose of vaccinia immune globulin intravenous, and started a 14-day course of twice-daily oral tecovirimat.

“She also received clindamycin and cephalexin because of concern about possible secondary bacterial infection,” the CDC reported. “Within 48 hours of treatment initiation, the fever and lymphadenopathy resolved, and the local pain and edema decreased.”

The occupational health office furloughed the patient from lab work for approximately four months, citing the local necrosis of the wound site and the risk for VACV transmission. Again, no secondary transmission or autoinoculation occurred.

Investigators determined that a genetically altered strain of VACV could have been involved in the needlestick. The patient was injecting multiple groups of mice with different strains, and did not recall which strain she used when the needlestick injury occurred.

“Although the patient had declined vaccination when it was initially offered, during this investigation she reported that she did not appreciate the extent of infection that could occur with VACV when vaccination was first offered,” the CDC concluded. “She also cited the challenges of managing the infectious lesion at the vaccination site and potential vaccination adverse events as factors contributing to her initial decision to decline vaccination.”

The CDC recommends vaccination for laboratorians who work with replication-competent VACV, unless vaccination is medically contraindicated. Counseling before working with VACV should include benefits of vaccination, risks of working with VACV in the laboratory, vaccination-associated adverse events, care of the vaccination site, and contraindications to vaccination.

“However, laboratories working with VACV set their own policies,” the CDC concluded. “ACAM2000 is a live-virus vaccine that produces an infectious vaccination site lesion. Appropriate vaccination site care requires careful monitoring of the site and adherence to infection control precautions until the crust separates and a new layer of skin forms.”

While laboratorians may wish to avoid the vaccine in lieu of these site management requirements, accidental inoculations may be a worse alternative. “[These] often occur in fingers or eyes, causing infections that present special concern for complications, and clinical management can be difficult,” the CDC warned. “In addition, laboratory exposures, unlike vaccination, do not have a controlled route of exposure or controlled dose.”

Hospital Employee Health sought further comment on this unusual case from CDC corresponding author Erin R. Whitehouse, PhD, MPH, in the following interview.

HEH: Can you comment on what type of lab this was, and the significance of using genetically modified strains of VACV? Was increased virulence a likely factor in the severity and duration of this infection?

Whitehouse: To protect the identity of the laboratory worker, we are not providing details about the laboratory itself. Vaccinia has been used for experimental vaccines and oncology research because it has a large, stable genome made of DNA, which makes it relatively easy to add genetic material (called generic inserts). We did not have reason to suspect that these inserts were more virulent to humans based on a review of scientific literature and an understanding of the purpose of the genetic insert. There is still much we do not know about how specific genetic changes to viruses, including VACV, might impact human health.

HEH: Can you elaborate on the “misconception among laboratory workers about the virulence of VACV strains?” Is this incident a cautionary tale of what can happen if a lab worker declines vaccination?

Whitehouse: Western reserve VACV is a replication-competent strain, which means it can replicate and cause infections in humans. In many laboratory strains, the thymidine kinase gene has been removed, which was thought to decrease the virulence of VACV. However, as noted in the Morbidity and Mortality Weekly Report, most laboratory-acquired vaccinia infections have been in VACV strains with the thymidine kinase removed. Because of the misconception that the thymidine kinase removal prevents infection, laboratorians may underestimate the impact of being infected with a strain of VACV. The specific risks of infection and adverse events from genetically modified strains of vaccinia are not well-known. Laboratorians also may underestimate their risk of having a laboratory accident, such as a needlestick. Laboratory workers should be clearly counseled on the potential risks of working with genetically modified vaccinia and encouraged to make a decision about vaccination in consultation with their physician.

HEH: Regarding the “importance of providing laboratorians with pathogen information and post-exposure procedures,” could that have prevented the situation of the two community physicians not seeming to understand the implications of the infection?

Whitehouse: We cannot comment on what might have happened in this scenario, but it is important that laboratories have clear post-exposure procedures and ensure that laboratory workers exposed to vaccinia have follow-up by a healthcare provider familiar with vaccinia. CDC and state and local health departments are available 24/7 to provide consultation for any healthcare provider who has a patient with a VACV exposure and would like additional information.

HEH: Can you comment further on the importance of these contact precaution measures to avoid secondary transmission and autoinoculation?

Whitehouse: It is important to monitor for lesions, and keep any lesions covered. Once lesions develop on the skin, they are infectious until the lesion forms a crust, the crust falls off, and new skin is present at the site. VACV is transmitted through direct contact with lesion material or through fomites (i.e. towels, bedding, clothing). A person can transmit VACV to other sites on his or her body through autoinoculation, or to other individuals. Post-exposure monitoring is important to help protect the person who has been exposed, as well as others. If a person is monitoring the infection site and covering any lesions that appear, then the risk of transmission is very low.

HEH: The worker apparently was worried about managing the inoculation site of a live-virus vaccine, but you underscore there may be a greater risk of “accidental inoculations” that often occur in fingers or eyes. Can you elaborate on this point, and the risk-benefit of VAVC vaccination?

Whitehouse: ACAM2000, a smallpox (vaccinia) vaccine licensed in the United States, is used for laboratorians working with Orthopoxviruses, including VACV. ACAM2000 contains a live VACV that causes an infectious lesion at the site of vaccination (typically the outer upper arm). The site is infectious until a crust forms, falls off, and new skin is present at the site, which typically takes four to six weeks. Appropriate vaccination care includes keeping the site covered to prevent infection to other parts of the body or to other people. Importantly, this is a known strain of VACV where the adverse events from vaccination are monitored through the Vaccine Adverse Events Reporting System at CDC, and by the military for military personnel. Thus, the risk of adverse events from vaccination are well-documented. As mentioned previously, the specific risks of infection from genetically modified strains of vaccinia are not well-known. In addition, the sites of accidental inoculations often are in areas like the eyes or fingers where there are higher risks of complications and that may be more difficult to cover to prevent further infections.

HEH: Were this lab’s policies typical or an outlier? It seems the worker was not adequately informed of the risk of VAVC, and unaware what to do after the exposure.

Whitehouse: We do not have enough information to comment on this. CDC does provide recommendations for vaccination of laboratory workers and others who may be at risk of occupational exposure with VACV through the Advisory Committee for Immunization Practices. However, laboratories set their own policies about vaccination.

HEH: Why was it necessary to furlough the worker for four months?

Whitehouse: The treating physician made determinations about the laboratory worker’s return to work based on her clinical status. We do not have enough details to comment specifically on all the factors related to her time off of work. However, VACV lesions are infectious until the scab has completely fallen off and new skin is present, a process that took several months in this case. Another contributing factor was the location on her finger, given that laboratory work with mice involves precision and fine motor skills.

REFERENCE

  1. Whitehouse, ER, Rao Ak, Yu YC, et al. Novel Treatment of a Vaccinia Virus Infection from an Occupational Needlestick — San Diego, California, 2019. MMWR Morb Mortal Wkly Rep 2019;68:943-946.