Challenges immense for infectious disease research in large animals

The challenges of using mice as part of infectious disease research are relatively minor when compared with studies involving large animals.

Consider the biosafety requirements for a tuberculosis study involving white-tailed deer. Think about the potential for injury to staff who are coaxing an unwilling bison into a holding pen for brucellosis research. Imagine the type of facility needed to process waste from 200 pigs housed together for a pseudorabies investigation.

These and other factors must be taken into account when planning and using laboratories for studies of communicable diseases in large animal species, explained a former Department of Agriculture official Nov. 10, 2003, at the annual meeting of the Conference of Research Workers in Animal Diseases in Chicago.

Prior to joining an architectural firm in Madison, Wis., as director of business development, Scott Rusk supported animal disease research as assistant director of the USDA's National Animal Disease Center in Ames, Iowa.

In Rusk's keynote address, he highlighted variables necessary to guarantee sound scientific results, personal safety, and animal care, and to prevent infectious materials from being released into the environment. The presentation was based on a report Rusk prepared with Kim A. Brogden, PhD, and Diana L. Whipple, of the National Animal Disease Center, and Dr. Thomas O. Bunn of the USDA National Veterinary Services Laboratories in Ames.

Laboratory mice, rats, and other small animals are housed in groups in biosafety cabinets and managed with relative ease. Not so with bovids, deer, and swine, which are also usually housed together over long periods.

A wide variety of special operational additions are, therefore, essential, including those that account for the animals' size and temperament. Rules and guidelines relating to their health and welfare must be observed while ensuring a biologically secure area.

"Agriculture has a biosafety flair to it that's quite a bit different than your standard (Centers for Disease Control and Prevention) and (National Institutes of Health) guidelines," Rusk said.

Facilities must be equipped with chutes and drop boxes so animals can be safely moved and restrained. To avoid injury to animals, floors can't be too rough or slippery. Steel is the preferred material for animal spaces because it allows for thorough fumigation and decontamination.

Proper cleaning of facilities enhances research data, Rusk noted, because pathogens from previous studies are prevented from contaminating later ones. It also protects staff from illness if the pathogen is zoonotic in nature.

Moreover, a facility's infrastructure must satisfy several demands. These include providing for the animals' various temperature and humidity requirements; rendering and sterilizing animal waste before releasing it into a public sewer system; and filtering air drawn in and expelled from the biocontainment area.

No detail is too small, according to Rusk. For instance, he recounted how he once witnessed pigs eat paint off walls he was "certain" were bare. In addition, a pen can be easy or difficult to clean, depending on the location of the floor drain. Maintenance crews are usually prohibited from biocontainment areas, so rooms should be designed with this in mind.

The importance of properly functioning equipment cannot be overstated. "If your squeeze chutes don't work well, you put a lot of people, as well as the animal, at risk," Rusk said.

Regardless of how state-of-the-art a facility is, the facility itself can't ensure absolute biocontainment. People are the key, according to Rusk. Staff must observe a number of protocols to avoid contaminating a project, but also for their own safety.

Close contact with animals is often necessary with large animals, hence increasing chances for exposure.

"We crawl inside the biosafety cabinets, face to face with the animals," he said, and added that the cabinet's protections are canceled at such times. Respirators, eye protection, disposable clothing, and hair covers are musts. Staff must shower before and after entering a biocontainment zone, Rusk added.

Medical surveillance is another part of this. It might be necessary for staff to be vaccinated or receive annual physicals.

Physical safety is also a concern. White-tailed deer weigh more than a hundred pounds, bison as much as a ton, so depending on the research animal, staff might be wearing knee and shin guards. "Sometimes, these guys look like they're dressed up to do battle or catch behind home plate," Rusk observed.

Federal regulations require additional biosafety precautions for research involving biologic agents that can cause serious or lethal diseases. Studies on M tuberculosis or St. Louis encephalitis virus, for example, are to be conducted only in a biosafety level 3 facility. Additional controls mandated by the level range from staff qualifications to the location of the facility itself.

Rusk concluded by saying the $445 million upgrade of the USDA laboratories in Ames will incorporate all the features highlighted in his presentation.