Is human exposure to veterinary vaccines a potential public health concern? There is currently limited understanding of the incidence of exposure of individuals to veterinary vaccines or of the consequences of such exposure. In addition, the potential for exposure and for adverse consequences secondary to exposure to veterinary vaccines may be increasing. The increased development and use of veterinary vaccines (including live vaccines), the increased aerosol administration of vaccines, and the increased proportion of individuals in the United States who are immunosuppressed and who may be exposed to these vaccines or to animals shedding the vaccine strains suggest that increased vigilance may be warranted.
The process for licensure of animal vaccines differs from that for human vaccines, and it is less rigorous. The USDA regulates veterinary vaccines, and the regulations are found in the Virus Serum Toxin Act in Title 9 of the Code of Federal Regulations . For the purpose of safety, the regulations state that a vaccine should not cause “undue local or systemic reactions”; for efficacy, the regulations state that a biological product “shall with reasonable certainty yield the results intended when used as recommended” [33, section 113.6]. In addition to requirements for safety, efficacy, and purity, the USDA performs a risk analysis before licensure to assess the risk posed by the vaccine to animals, human health, and the environment; the extent of this analysis varies according to vaccine (Louise Henderson, USDA, personal communication). The FDA regulates currently administered human vaccines and vaccines under investigation; there is a lengthy prelicensure process that may involve thousands of individuals in clinical trials.
Surveillance is conducted to monitor adverse effects of vaccines in animals, and problems have been documented . Safety concerns have included instances of failure to inactivate the virus sufficiently, resulting in disease in the vaccinated animals. This has been documented for the foot-and-mouth vaccine, as well as for the Venezuelan equine encephalitis vaccine. In addition, there have been adverse reactions to vaccine that were associated with the residual virulence of the vaccine organisms. The attenuated vaccine strains may be capable of producing disease in immunosuppressed and/or pregnant animals and have occasionally caused disease in healthy animals . There have also been examples of vaccines that induced lethal disease when administered to a species other than the target species .
In addition to problems associated with the vaccine virus strain itself, there are numerous examples of vaccines that have been contaminated with extraneous microorganisms, including live Mycoplasma organisms and bluetongue virus . In the early 1990s, a modified live virus vaccine containing canine distemper virus, canine parainfluenza virus, canine adenovirus-2, and canine parvovirus was reported to have caused abortion and death when administered to pregnant dogs; the vaccine was found to be contaminated with bluetongue virus [34, 35]. Bluetongue virus causes disease in wild and domestic ruminants, and it was not known to cause natural infection and disease in dogs.
Avirulent live vaccines are considered more efficient for preventing the spread of some diseases, such as those due to Salmonella infection in poultry raised for human consumption. A French study of several isolates of 3 live vaccine strains of S. enterica serotype Typhimurium demonstrated that the vaccine strains in the environment of the inoculated animals persisted for at least 1 month after vaccination . Some vaccine strains persisted in the liver and gut of poultry for at least 10 days. Two of the 3 strains, including 1 commercially available in the United States, showed evidence of genetic instability, but the investigators were unable to link the genetic changes to an impact on safety . A number of issues are raised by such studies, including the public health impact, if any, of animals raised for human consumption that are infected with a vaccine strain at the time of slaughter, the potential impact of the persistence of the virus in the environment, and the uncertainty posed by the genetic instability of some veterinary vaccines.
When physicians see patients with a zoonosis and query about exposure to sick animals, they may also want to query about exposure to live vaccines, to the environment in which live vaccines are administered, or to animals to which live vaccine has recently been administered. Occupational studies of exposure and outcome may be useful. More information is needed regarding the potential misuse of veterinary vaccines. Human misuse may be more common than many health practitioners realize. In 1998, the National Poison Control Center (Washington, DC) registered >3700 adverse events associated with human use of medications intended only for animal use.
Veterinarians should be instructed to take precautions to avoid exposing themselves or others who are in proximity to the animals to the vaccine (e.g., inadvertent administration of aerosol vaccine to an unsuspecting pet owner). Should immunosuppressed patients be warned to decrease the risk of exposure to aerosol and non–aerosol formulations of live vaccines? Should warning labels be placed on veterinary vaccines to avoid human exposure, and should individuals be aware that human safety studies have not been conducted? To what agency or organization should illness suspected to have resulted from human exposure to veterinary vaccines be reported? Should there be more safety testing, including increased testing of the genetic stability of the vaccine strain? Those who use veterinary vaccines should understand potential human health hazards and should know to whom to report suspected adverse consequences of exposure.
Veterinary vaccines have provided enormous economic and health benefits to the animal industry, and they have dramatically reduced the incidence of many zoonotic infections in humans. At the same time, as the frequency and administration of animal vaccines increase, we must be vigilant regarding human exposure and safety. Health consequences of human exposure to animal vaccines or vaccine strains cannot be quantified if they are not recognized and reported. For some diseases, such as brucellosis and vaccinia, a link has been clearly documented. For others, such as disease due to B. bronchiseptica infection, additional study to establish whether a link exists is needed. Some form of postmarketing surveillance for human adverse events should be considered when new vaccines are introduced, especially live vaccines for zoonotic diseases. Awareness of the potential for adverse events after exposure to animal vaccines or to animals vaccinated with a live vaccine should increase among physicians, and robust mechanisms of reporting, in addition to follow-up investigation, should be developed and implemented for suspected adverse events.