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Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference (2000)

Chapter: Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice

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Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
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Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice

Toshiyuki Shibahara

Vice Director and Associate Professor

Laboratory Animal Research Center

Faculty of Medicine, Tottori University

Yonago, Japan

MICROBIOLOGIC CONTAMINATION IN LABORATORY RATS AND MICE

Recently, the Japanese Association of Laboratory Animal Facilities of National Universities (JALAN; Figure 1) addressed the issue of a possible microbiologic contamination problem upon delivery of laboratory rats and mice to national universities and associated institutions. JALAN's Working Biosafety Committee (of which I am a member) has begun an investigation, and results have indicated that the problem is caused by the discrepancy between the sterility monitoring policies of the sender and the recipient. In some institutions, potentially harmful microbes/parasites (e.g., pinworms) are considered insignificant, and laboratory animals that are comtaminated with such microbes/parasites are sent or accepted without being examined. I would like to call attention to this problem and propose countermeasures.

Contamination of laboratory animals introduced both domestically and from abroad and the discrepancy between senders' and recipients ' sterility policies were reported by Dr. Mannen (Oita Medical University, Japan) at the last US/Japan conference (Mannen 1998). Dr. Mannen stated that many members of JALAN encounter subtle differences between the required microbiologic monitoring/inspection items of animals being distributed among national, public, and private colleges, as well as other academic institutions, and that this type of problem also exists with international shipping. Problem cases are increasing particularly with the increase of transported gene-manipulated animals (e.g., transgenic/knockout mice). For this reason, the JALAN Biosafety Committee is

Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×

FIGURE 1 Organizational chart of animal centers in Japanese universities. Adapted from Mannen, K. 1998. Definition of microbiologic status of rats and mice: The need for methods of defining flora: International standards for terminology. In: Microbial and Phenotypic Definition of Rats and Mice: Proceedings of the 1998 US/Japan Conference. Washington DC: National Academy Press. p. 24–27.

dedicated to the difficult task of formulating guidelines on the delivery and acceptance of laboratory rats and mice in national universities in an effort to establish uniformity in microbiologic monitoring/inspection items.

The results of inspecting mice facilities at the Central Institute of Experimental Animals of Japan for parasites over 3 years are shown in Table 1. Parasites were detected in 125 of 444 facilities. Some of the parasites are nonpatho-

TABLE 1 Parasitologic Monitoring in Mice Experimental Facilities (1996-1998)

Parasites

Number of Positive Facilities (%)

Octomitus pulcher

41 (9.2)

Chilomastix spp.

18 (4.1)

Tritrichomonas spp.

18 (4.1)

Syphacia obvelata

14 (3.2)

Entamoeba muris

10 (2.3)

Pneumocystis carinii

9 (2.0)

Aspiculuris tetaptera

7 (1.6)

Spironucleus muris

3 (0.7)

Unknown protozoa spp.

5 (1.1)

Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×

genic; however, others (e.g., Aspiculuris and Spironucleus, from both domestic and international sources) are pathogenic.

Members of the Biosafety Committee have been reconsidering the pathogenicity of specific pathogens (Itoh 1998). They currently recommend monitoring for the pathogens listed in Table 2, with optional attention to nonpathogenic protozoa. Although Committee members discussed the possible deletion of nonpathogenic protozoa (e.g., trichomonads) from the list, because they are sometimes found and/or listed in health reports from outside a facility, they ultimately decided to retain the item in the list.

PINWORMS AS POSSIBLE INDICATORS OF BIOLOGICALLY CONTAMINATED ANIMAL FACILITIES

Some Committee members considered the presence of nonpathogenic protozoa to reflect the level of microbiologic control among animal facilities. In the case of pinworms, the ICLAS monitoring center has identified pinworms as category E (i.e., a nonpathogenic parasite and mere indicator). From my experience, I have no doubt that pinworms have caused diseases, have affected their physiologic functions, and have influenced experimental results. Reports of pinworm infection affecting experimental results include that of Wagner (1988), who reported definite growth differences between pinworm-free and pinworm-infected rats. Sato et al. (1995) also reported that antibodies against Syphacia obvelata somatic antigen were detected in experimental infection of pinworms in mice. Thus, it is clear that pinworms affect infected animals ' physiologic functions and thereby influence experimental results. In my opinion, laboratory animal scientists should no longer minimize the influence of parasites. Because the measures taken to combat parasitic contamination in laboratory rats and mice have conspicuously lagged behind those taken against other pathogens (e.g., viruses and bacteria), parasites may currently be found even in animal facilities that appear to be well maintained and without microbiologic problems.

From an international point of view, I highly recommend international unification and harmonization of allowable microbiologic monitoring/inspection items of animals.

NEED FOR ELIMINATION OF PARASITES

In my experience with pinworm infection of laboratory mice, parasites have been entirely eliminated from a colony by mixing anthelmintic with feed and/or spraying the animals or bedding with ivermectin. Although these methods (especially the use of ivermectin) do involve some risk and are therefore not recommended, they are easier and more convenient than the embryo-transplant method. Some researchers complain about the use of anthelmintic; however, they should not overlook the spread of parasite infections like pinworms. I believe these methods are necessary to eradicate pinworms and other parasitic infections from mouse and rat colonies.

Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×

TABLE 2 Microbes/Parasites in Mice and Rats for the Subject of Microbiologic Monitoring in University Animal Facilities

Mouse Pathogen

Categorya

Frequencyb

Microbiological statusc

Inspection

Mouse hepatitis virus

B

Minimum

Periodically

Sendai virus

B

Minimum

Periodically

Ectromelia virus

B

Minimum

Nonperiodically

Lymphocytic choriomeningitis virus

A

Minimum

Nonperiodically

Mouse rotavirus (EDIMV)

B/C

Common

Nonperiodically

Mouse parovirus (MVM/MPV)

C

Common

Nonperiodically

Mouse encephalomyelitis virus (TMEV)

C

Common

Nonperiodically

Pneumonia virus of mice (PVM)

C

Common

Nonperiodically

Mouse adenovirus

C

Common

Nonperiodically

Reovirus type 3

C

Common

Nonperiodically

Lactic dehydrogenase elevating virus (LDEV)

C

Common

Nonperiodically

Mycoplasma pulmonis

B

Minimum

Periodically

Salmonella spp.

A

Minimum

Periodically

Clostridium piliforme (Tyzzer's organism)

C

Minimum

Periodically

Corynebacterium kutscheri

C

Minimum

Periodically

Pasteurella pneumotropica

C

Common

Periodically

Cilia-associated respiratory (CAR) bacillus

C

Common

Nonperiodically

Escherichia coli O115a, c:K(B)

B/C

Common

Nonperiodically

Helicobacter hepaticus

C

Common

Nonperiodically

Pseudomonas aeruginosa

D/E

Excellent

Peri./nonperi.

Staphylococcus aureus

D/E

Excellent

Periodically

Pneumocystis carinii

D

Excellent

Nonperiodically

Pathogenic protozoa

 

Giardia muris

C

Common

Periodicallyd

Spironucleus muris

C

Common

Periodicallyd

Nonpathogenic protozoa

 

Trichomonads, etc.

E

Excellent

Periodicallyd

Helminths (pinworms)

C

Common

Periodicallyd

Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×

Rat Pathogen

Categorya

Frequencyb

Microbiological statusc

Inspection

Sialodacryoadenitis virus (SDAV)

B

Minimum

Periodically

Sendai virus (HVJ)

B

Minimum

Periodically

Hantavirus

A

Minimum

Periodically

Rat parvovirus (KRV/H-1/RPV)

C

Common

Nonperiodically

Mouse encephalomyelitis virus (TMEV)

C

Common

Nonperiodically

Pneumonia virus of mice (PVM)

C

Common

Nonperiodically

Mouse adenovirus

C

Common

Nonperiodically

Reovirus type 3

C

Common

Nonperiodically

Mycoplasma pulmonis

B

Minimum

Periodically

Salmonella spp.

A

Minimum

Periodically

Clostridium piliforme (Tyzzer's organism)

C

Minimum

Periodically

Corynebacterium kutscheri

C

Minimum

Periodically

Bordetella bronchiseptica

C

Minimum

Periodically

Pasteurella pneumotropica

C

Common

Periodically

Streptococcus pneumoniae

C

Common

Nonperiodically

Cilia-associated respiratory (CAR) bacillus

C

Common

Nonperiodically

Pseudomonas aeruginosa

D/E

Excellent

Peri./nonperi.

Staphylococcus aureus

D/E

Excellent

Nonperiodically

Pneumocystis carinii

D

Excellent

Nonperiodically

Pathogenic protozoa

 

Giardia muris

C

Common

Periodicallyd

Spironucleus muris

C

Common

Periodicallyd

Nonpathogenic protozoa

 

Trichomonads, etc.

E

Excellent

Periodicallyd

Helminths (pinworms)

C

Common

Periodicallyd

aCriteria used for selection of test items in the ICLAS monitoring center.

bFrequency of occurrence during the past two decades in Japan. , rare; , often; , very often.

cMinimum: These pathogens should be negative. Common: It is desirable that these pathogens are negative. Excellent: It is desirable that these pathogens are negative in immuno-insufficient/deficient mice.

dInspection methods to be recommended are to examine small/large intestine contents. (Modified in part from Mannen, 1998)

Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×

CONCLUSION AND RECOMMENDATIONS

  • Measures to counteract parasitic contamination in experimental animals, especially rats and mice, lag conspicuously behind those that counteract other pathogens.

  • Parasites often serve as indicators of the level of microbiologic control among animal facilities. However, because some parasites may affect experimental data, their existence and species name should be clearly indicated in the health monitoring reports.

  • The pathogenecity of parasites should be reexamined, even if they are considered nonpathogenic to the animals. An international scheme for unification/harmonization of test results and allowable conditions should be devised.

  • Parasites should be eliminated as much as possible. The methods recommended are as follows:

    1. mixing anthelminthic with feed;

    2. spraying animals/bedding with anthelminthic; and/or

    3. cleaning the colony using a method such as embryo transplant.

REFERENCES

Itoh, T. 1998. Quality testing system for SPF animals in Japan and problems in the management of such systems. In: Microbial and Phenotypic Definition of Rats and Mice: Proceedings of the1998 US/Japan Conference. Washington, DC: National Academy Press. p. 15-23.

Mannen, K. 1998. Definition of microbiologic status of rats and mice: The need for methods of defining flora: International standards for terminology . In: Microbial and Phenotypic Definition of Rats and Mice: Proceedings of the 1998 US/Japan Conference. Washington DC: National Academy Press. p. 24-27.

Sato, Y., H.K. Ooi, N. Nonaka, Y. Oku, and M. Kamiya. 1995. Antibody production in Syphacia obvelata in infected mice. J. Parasitol. 81:559-562.

Wagner, M. 1988. The effect of infection with the pin worm (Syphacia muris) on rat growth. Lab. Anim. Sci. 38:476-478.

Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×
Page 21
Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×
Page 22
Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×
Page 23
Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×
Page 24
Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×
Page 25
Suggested Citation:"Necessity of Reexamining the Pathogenicity and Elimination of Parasites in Rats and Mice." National Research Council. 2000. Microbial Status and Genetic Evaluation of Mice and Rats: Proceedings of the 1999 US/Japan Conference. Washington, DC: The National Academies Press. doi: 10.17226/9987.
×
Page 26
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US/Japan meetings on laboratory animal science have been held virtually every year since 1980 under the US/Japan Cooperative Program on Science and Technology. Over the years these meetings have resulted in a number of important documents including the Manual of Microbiologic Monitoring of Laboratory Animals published in 1994 and the article Establishment and Preservation of Reference Inbred Strains of Rats for General Purposes. In addition to these publications, the meetings have been instrumental in increasing awareness of the need for microbiologic monitoring of laboratory rodents and the need for genetic definition and monitoring of mice and rats.

In cooperation with the Comparative Medicine section of NCRR/NIH, the ILAR Council and staff are pleased to become the host for this important annual meeting and look forward to participating in future meetings. The support and sponsorship of NCRR (P40 RR 11611) in the United States and the Central Institute for Experimental Animals in Japan are gratefully acknowledged. Bringing together the leading scientists in the field of laboratory animal care has resulted in increased understanding of American and Japanese approaches to laboratory animal science and should continue to strengthen efforts to harmonize approaches aimed at resolving common challenges in the use of animal models for biomedical research and testing. This effort to improve understanding and cooperation between Japan and the United States should also be useful in developing similar interaction with other regions of the world including Europe, Australia, and Southeast Asia.

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