Health and Safety
Executive / Commission
Infections at work and GMOs
1 In September 2002 we began an investigation into a laboratory acquired vaccinia virus infection, which was reported under the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR), because the infected individual was hospitalised with what is thought to have been a secondary bacterial infection. In this instance no particular event could be identified as having been responsible for the infection. However, it is possible that the infection resulted from contact with a contaminated surface, piece of equipment or object. Although the individual had received training in laboratory techniques and the risks of working with vaccinia virus, they were not aware of the signs of vaccinia infection and therefore did not realise that they had been infected.
2 It is believed that the vaccinia virus involved in the infection was a recombinant WR strain virus with a deletion of the thymidine kinase gene. WR strain is a murine neurovirulent strain frequently used in laboratories because it grows to high titre. Although thymidine kinase negative viruses are less pathogenic for mice than wild-type viruses, laboratory acquired vaccinia infections such as this demonstrate that these viruses are capable of infecting humans.
3 This is not the only case of a laboratory acquired recombinant vaccinia virus infection that we are aware of. In one case, a technician who had been vaccinated 2 years previously, accidentally inoculated himself whilst working with recombinants based on Thymidine kinase negative WR strain. The technician developed lesions after 5-6 days, which healed spontaneously. (Lancet 1991 vol 338 p459). In another case, a postgraduate student was admitted to hospital with a high fever and severe inflammation and swelling of the face. He had recently had an eyebrow pierced and doctors treated him for a suspected bacterial infection. He also developed a lesion on a finger, which a colleague suspected might be a vaccinia virus lesion. This diagnosis was confirmed serologically and doctors concluded that the patient had infected the open eyebrow wound through contact with the lesion on his finger. The infection resolved in a week and the patient was discharged. The student had been working with genetically modified vaccinia virus, and may have been accidentally infected whilst inoculating mice as part of his research, although he was unaware of any accidental inoculation or spillage of the virus and was wearing gloves during experimental procedures. Other cases of laboratory acquired vaccinia virus infections are well documented (J. Invest Dermatol 2003 vol 120 p345, J. Invest Dermatol 2003 vol 120 p 356).
4 Vaccinia virus is best known as the live attenuated vaccine used in the smallpox eradication campaign. Primary vaccination in humans causes a vesicular lesion at the site of inoculation usually associated with a local infection and, rarely, a viraemia between the third and tenth day. After about 7 days, the lesion crusts over and detaches, leaving a characteristic scar. Despite millions of individuals being vaccinated without effect, even vaccine strains (primarily Lister and Wyeth strains) can cause infections in humans.
Potential sources of infection
5 It is well known that vaccinia and other poxviruses have the
capacity to survive for considerable periods in dried material such
as detached vaccination scabs, but it is less well appreciated that
survival in aqueous solutions can be for several weeks. Live virus
can also be isolated from solid surfaces and fabric for as long as
two weeks after contamination. For laboratory workers, ingestion,
inoculation via needles or sharps, and droplet or aerosol exposure of
mucous membranes or broken skin are possible routes of infection.
Laboratories working with vaccinia and other poxviruses should have
suitable local rules to control these potential sources of infection,
including suitable procedures for decontamination of equipment and
surfaces.
6 As work with Class 2 organisms such as vaccinia virus requires restricted access, ideally only those who work with the virus should have access to the areas where the virus is used. Where vaccinia viruses are used in multi-user facilities, all users must be familiar with the risks associated with vaccinia and be trained to recognise the signs of vaccinia virus infection. Photographs of VV infections are available by searching for 'smallpox' at http://phil.cdc.gov/phil/quicksearch.asp. Photographs of vaccinia virus infections can also be found in 'Vaccinia (Smallpox) Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001', available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5010a1.htm.
Risk awareness
7 Vaccinia virus is categorized by ACDP as a hazard group 2
biological agent in recognition that it may cause particularly severe
disease during pregnancy, in people with active skin disorders such
as eczema or psoriasis, or in immuno-compromised individuals such as
those infected with HIV. Indeed a number of vaccinia virus vaccine
associated deaths of HIV positive individuals have been reported. It
is well documented that vaccinia can be passed to close contacts of
vaccine recipients generally with little adverse consequence.
Therefore, although an individual with a laboratory-acquired
infection is unlikely to receive the virus dose given for vaccination
purposes, close contacts, particularly those with contraindications
for vaccination, may also be at risk. All personnel who work with
vaccinia virus should be: trained to recognise vaccinia virus
infection; made aware of the possibility of human-to-human
transmission; and be aware of the increased risk to those with
eczema, those who are immuno-compromised, or those who are
pregnant.
Informing medical advisers
8 People who work with infectious agents or who work in areas where
they could be in contact with infectious agents should consider
informing their medical adviser of the nature of their work, if they
believe that it could be relevant to their condition.
Reporting to the Competent Authority
9 In addition to the requirements of RIDDOR, Regulation 21 of the
Genetically Modified Organisms (Contained Use) Regulations 2000
places a duty on those working with GMMs and GMOs to report
accidents, incidents and infections to the Competent Authority.
Further information is available in interim guidance, 'Notifying accidents' available in ACGM
Newsletter 32.