Risks of Infection among Laboratory Rats and Mice at Major Biomedical Research Institutions

Adventitious infections are among the most pervasive problems encountered in the use of laboratory mice and rats. Small laboratory rodents are susceptible to more than 50 viral, bacterial, parasitic, and fungal agents, which include well-known organisms such as mouse hepatitis virus and Mycoplasma pulmonis (Bhatt and others 1986; Compton and others 1993; NRC 1991; Percy and Barthold 1993) as well as emerging agents such as the recently discovered mouse and rat parvoviruses and Helicobacter species (Fox and Lee 1997; Jacoby and others 1996). Some of these agents incite overt disease, but most cause subclinical infections that can, nonetheless, significantly alter research results. They usually gain entry through infected animals or animal products such as serum, cells, or transplantable tumors. Expanding exchanges of animals and animal products among laboratories throughout the world have amplified the risks for introducing infection, especially among colonies that are not protected by stringent preventive measures. Risks from infection also are increasing due to the availability of genetically engineered mice, whose responses to infection and disease can be unpredictable. Hundreds of novel mouse strains have been developed, and their use will continue to grow as advances in biotechnology increase their value to research. This trend is adding significantly to the size of institutional rodent colonies and to the complexity of rodent health care. The prevention of deleterious infections among valuable, densely housed rodents, such as transgenic mice, requires timely testing, appropriate housing, rapid diagnosis, and control of worrisome outbreaks. These measures, and the use of animals with known microbial profiles, are sound insurance against tainted research. ability of animal-based research. However, attempts to assess the effectiveness of specific pathogen-free (SPF) housing, husbandry, and health care have been sparse. The last broad survey on the microbial status of mouse and rat colonies in the United States, which focused on the prevalence of infections in commercial breeding colonies (Casebolt and others 1988), was published about 10 years ago. A 1993 survey of laboratory animal use from the National Center for Research Resources (NCRR 1997) described responses about health care staffing for animal resources but did not inquire about the health status of animal colonies. Because of the increasing reliance of biomedical science on genetically engineered rodents and the deleterious influence of infection on rodentbased research, we recently surveyed major research centers throughout the United States for the presence of detrimental infectious agents in mouse and rat colonies. A summary of the results was published in July 1997 ( Jacoby and Lindsey 1997). This article provides a more complete synopsis of survey results, which indicate that risks from infection remain high despite improvements in rodent health care. The current survey queried animal resource directors at institutions comprising the top 102 recipients of National Institutes of Health (NIH) funds in 1996. Seventy-two institutions (71%) from 35 different states responded. Sixty-five of the respondents were colleges or universities, but 6 research institutes and 1 teaching hospital were included (Table 1). Collectively, they received more than $5.2 billion in annual NIH support during fiscal year 1995-1996 (slightly more than half of the NIH extramural research budget)—about $2.1 billion of which involved animal-related research—and used more than 3 million mice and 1 million rats.