Office of Research Rodent Health Monitoring Programs - Office of Research

Rodent Health Monitoring Programs

Attending Veterinarian Summary

RODENT HEALTH MONITORING PROGRAMS

June 16, 2008
Rodent health monitoring programs, rodent health surveillance, or sentinel monitoring programs, are designed to detect subclinical infections of rodents that potentially have detrimental effects to research. The program is tailored to the needs of the research.  There are many variations to developing and implementing a health monitoring program, but to maintain a constant standard of care at UC Davis, the Office of the Attending Veterinarian has developed a program of minimum standards. This program will provide essential information to vivarium managers, the veterinary staff, and the investigator.

Selection of Agents to Screen:

There are over 30 pathogens of rodents that can cause subclinical to clinical infections. Infection with these agents can present an unwanted variable resulting in aberrant effects on research results. Many of these agents are rare, as commercial vendors have been providing pathogen free rodents. However, there are still some that are commonly encountered in the research setting. The agents chose to screen are those more commonly encountered in laboratory rodents that are primary rodent pathogens, highly contagious, effect research results, are potential zoonotic diseases (disease transmitted from animal to human beings), or are commonly requested by other institution receiving rodent originating from UC Davis.

There are two levels of screening-quarterly testing and biannual testing which are outlined in the table below for each species. This is a modification of the screening performed in the past by increasing the frequency of the more common pathogens, and decreasing the frequency of the less common pathogens. This is the recommended list of routine screening of all rodent colonies of campus. More thorough testing may be required for barrier maintained rodents or defined flora rodents.

Mouse
Quarterly Testing
Serology- MHV, EDIM, TMEV, MVM, MPV, Ectromelia, Mycoplasma pulmonisParasitology- Ecto- and Endo- parasite,

Biannual Testing
Serology- Quarterly testing plus Norovirus, REO3, LCM, Sendai, PVM, Adenovirus,
Bacteriology- Respiratory and enteric cultures.  Additional bacterial screening is done in barrier, high risk or immune compromised colonies that may include helicobacter PCR and Pneumocystis screening.
Parasitology- Ecto- and Endo parasites.

Rat
Quarterly Testing
Serology- RCV, KRV, H1, RPV, Sendai, Mycoplasma pulmonis,Parasitology- Ecto- and Endo- parasite.

Biannual Testing
Serology- Quarterly testing plus REO3, PVM, Hantavirus, LCM, TMEVBacteriology- Respiratory and enteric cultures; Parasitology- Ecto- and Endo parasites.

Hamsters
Quarterly Testing
Serology- Sendai, PVM, LCMParasitology- Ecto- and Endo parasites.

Biannual Testing
Same as Quarterly testing

Guinea Pigs
Quarterly Testing
Serology- Sendai, PVM

Biannual Testing
Same as Quarterly testing plus LCM

Animals to be Screened:

A health monitoring program is designed to detect infections that may be present within the colony without testing all the animals within the colony. As such sentinel animals are maximally exposed to all the other animals in the room, typically using soiled bedding transfer. This involves mixing the soiled bedding of colony animals and giving it to sentinel animals to expose them. The entire procedure can be obtained by viewing the SOP available from the Campus Veterinarian’s Office at 530-752-7244 or animaltransfer@ucdavis.edu . It also requires that the animals to be screened are carefully selected. There is a tremendous amount of strain variability in response to infectious agents. When selecting an appropriate strain one needs to use an immunocompetent animal that is susceptible to disease and develops strong antibody responses. Examples of strains of mice that meet this criteria are outbred CD1, BALB/c, and C3H mice. Strains that are not sufficient are C57BL/6, SCID, or transgenic animals.

The use of colony culls is an excellent adjunct to the use of soiled bedding sentinels, but should not be the main source of sentinels as it would be easy to miss infections with a low prevalence.

Numbers to be Screened:

The number of animals chosen to be screened can be determined using a statistical formula. This formula has a number of assumptions which include: a population of at least 100, the pathogens is randomly dispersed throughout the colony, there is no sex predilection, the percentage of infected animals should be known, and the tests used for screen are 100% sensitive and specific. The formula used is:

Log 0.05
Log N
= number to be sampled

Where N = the percentage of uninfected animals and Log 0.05 indicates a 95 percent confidence level.

Using this formula the following table highlights the sample size required to detect at lest one positive animal with a 95% confidence.

Expected Incidence
of Infection
in the Population (%)
Sample Size*
90 2
80 2
70 3
60 4
50 5
40 6
30 9
20 14
10 29
1 298

Most viral disease have an incidence of infection of 30-40 percent in conventional housing situations, meaning 6-9 animals per 100 should be screened routinely.

Unfortunately, many of the assumption are unknown, inappropriate or significantly changed because of husbandry practices often resulting in an increased number of animals required to be screened to ensure the same confidence.

Obviously it is impractical financially to screen with this degree of rigor. However, to improve our ability to detect pathogens and provide reasonable assurances that we will detect a pathogen, the Attending Veterinarian has decided that for mice 2 sentinels per 80 colony boxes is sufficient.

Frequency of Screening:

The frequency of screening is set at quarterly intervals because this provides an adequate amount of time for potentially infected colony animals to shed the pathogens, expose the sentinels, and allow for the sentinel animals to develop a detectable immune response. Therefore sentinel animals are replaced quarterly.

Vivaiarium management:

Knowledge of the health status of rodents allows for more effective management practices to control the spread of disease. Many vivaria house rodents for multiple investigators, many of whom want to maintain pathogen free, or specific pathogen free rodents. Knowledge of the health status allow vivaria managers to make the appropriate management decisions regarding traffic flow of personnel and equipment.

In addition there is an increase in interdepartmental collaborations resulting in the movement of animals from one vivarium to another. To properly manage this movement to prevent the spread of an unwanted disease, the health status across campus needs to be known. For example, there is a core small animal imaging facility located in the basement of the Genomics and Biomedical Sciences Facility which images animals all over campus. To prevent the inadvertent spread of disease between vivaria it is important to know the current health status.

Effects on Research:

Pathogens of rodents have numerous documented effects altering research results (Baker, DG. Natural pathogens of laboratory mice, rats, and rabbits and their effects on research. Clin Microbiol Rev. 1998 Apr;11(2):231-66. The sentinel program provides assurance to investigators that there are not unwanted variable affecting their research. To provide a brief example, mouse parvovirus causes persistent infection and has been demonstrated to alter immune responses. The veterinary care program must address and recognize that most investigators want to maintain pathogen free colonies to deliver quality research.

Expectations from other institutions:

Intercollegiate collaboration have resulted in an increasing movement of rodents (particularly transgenic mice) between institutions. Each institution has developed its own standard for what is an acceptable health status for receiving animals. The agents selected also address the most common pathogens others expect to be evaluated. As such the recommended sample size, frequency and tests are consistent with the ‘industry’ standard.