Nowadays, it is unquestionable the importance of the laboratory animal health in research. Improving the microbial quality animal allows to reduce (or eliminate) the negative effects of pathogen agents (not associated with the objective of the study) in the expected experimental results. Health monitoring programs are used as preventive tools in animal facilities, although, in some circumstances many facilities cannot or have problems for establishing appropriate strategies. The present text attempts to bring the reader's interest to the laboratory animal health. A better awareness about this topic will allow a better use of animals in research.
Keywords: Laboratory animal, microbial status, health monitoring, recommendations
Nowadays, it is unquestionable the importance of the laboratory animal health in research. Natural pathogens as viral, bacterial, parasitic, and fungal agents may be present in laboratory animal, without provoking signs of disease1. Many of infectious agents have been described as factors that may alter host physiology, perturbing experimental results.2 Important advances related to environmental control, hygiene, nutrition, and animal husbandry as gnotobiotic derivation3 and transgenic techniques4, have allowed a significant reduction (and sometimes a complete elimination) of pathogens found in laboratory animals.
At present, transport of animals between facilities for research purposes is a common practice. This enables to transmit unwanted microbiological agents between institutions. Consequently, animal facilities require correct health monitoring methods, for recognizing animal health status, as well as the rapid detection of an infectious agent and validate measures of prevention to the admission of infected animals. Microorganisms can be also introduced through contaminated biological reagents (isolated organs or cells, tumors, embryonic cells, sera, others), altering in vitro experiments. Some pathogens can “enter” to the animal facility by water, food, bedding material or other contaminated objects, which would be avoided by evaluating their microbial quality prior to be used. It is also remarkable the apparent risk caused by microorganisms from the animal house staff, especially for immunosuppresed animals. In addition to regular microbial checks, it is also required to validate serological and biochemical diagnostic protocols.
Although animal facilities are designed as a strict sanitary barrier, health monitoring is needed for the detection and identification of pathogens as a preventative tool. Health monitoring remains as a topic of interest and over the years proposals have been emerging. The Federation of European Laboratory Animal Science Associations (FELASA) has been releasing guidelines and recommendations (not regulatory in nature) on several laboratory animal science disciplines. FELASA recommendations offer important support in to advance and harmonize the development of all aspects of laboratory animal science and practice, not only in Europe but also in the worldwide. The first publication focused on health monitoring of rodent and rabbit breeding colonies and encouraged interest in this type of suggestions5. The frequency of animal monitoring, the sample size, the observation of pathologic lesions, a list (flexible) of bacterial, fungal, viral, and parasitic agents to be monitored were included in this revision. Moreover, a standard health monitoring report was proposed; the information compiled from husbandry practices, breeding and clinical observations provide information about the health condition of experimental animals. Afterwards, recommendations on the health monitoring of breeding colonies and experimental units of cats, dogs, and pigs6, and about small ruminants7 were also reported by FELASA.
Scientific knowledge increases over time inducing updates of the health monitoring recommendations8. The addition of new infectious agents that are now identified in rodent colonies (such as Helicobacter spp., mouse rotavirus, mouse adenovirus, mouse and rat parvoviruses), new diagnostic techniques, a better use of sentinel animals, and the reporting of the results are factors to be included in a recent revision.
In 2007, International Council for Laboratory Animal Science (ICLAS)9 established a Performance Evaluation Program for Diagnostic Laboratories. It offers subscribing laboratories the opportunity to evaluate their diagnostic methods through the analysis of well characterized specimens for serology, bacteriology, and PCR testing, improving the diagnostic performance through a process of self-assessment.
Recently, international working group collaborations on health monitoring of rodents have emerged (American Association for Laboratory Animal Science (AALAS) and FELASA10. The main goal is to join efforts in order to reach an international harmonization of health monitoring, in which definitions of quality and standards would be recognized. Also, transportation of laboratory rodents and the assessment of the microbiological status of them (such as; agents or methodology for diagnosis) are worldwide objectives that must be achieved.
No doubt exists in that standardized health monitoring is required. However, benefits but also limitations of all these guidelines and recommendations are debated11. The first limitation could be that animal facilities are not equal. The protocol type of investigation establishes the number and variety of microbial agents to be tested; the number of animals to be tested (depending on the virulence of the pathogen); the use open cages in conventional or barrier housing; individually ventilated cages or isolators; the sentinel program, among other parameters. A second (and a very important) limitation could be the cost of monitoring and diagnostic practices.
The health state of laboratory animal must be taken into account throughout the experimental time course. Interferences caused by infectious agents could be related to differences in the experimental results obtained. However and unfortunately, only successful results tend to be published. Without the microbial interferences, the number of animals used for scientific purposes could decrease and also prevent the unnecessary distress caused by microorganisms. Undoubtedly, health monitoring practices are in accordance with the achievement of the three Rs (replacement, reduction and refinement) of Russell and Burch (1959), improving the quality of science and, in consequence, life quality.
1 . Baker DG. Natural pathogens of laboratory mice, rats, and rabbits and their effects on research. Clin Microbiol Rev 1998, 11:231-66.
2 . Nicklas W, Homberger FR, Illgen-Wilcke B, Jacobi K, Kraft V, Kunstyr I, Maehler M, Meyer H, Pohlmeyer-Esch G. Implications of infectious agents on results of animal experiments. Lab Anim 1999, 33: 39:87.
3 . Owens WE, Berg RD. Derivation of a breeding colony of germ-free athymic mice by cesarean section and foster nursing. J Immunol Methods 1981, 42 :115-9.
4 . Rülicke T, Montagutelli X, Pintado B, Thon R, Hedrich HJ. FELASA guidelines for the production and nomenclature of transgenic rodents. Lab Anim 2007, 41:301-11.
5 . Kraft V, Blanchet health monitoring, Boot R, Deeny A, Hansen AK, Hem A, van Herck H, Kunstyr I, Needham JR, Nicklas W, Perrot A, Rehbinder C, Richard Y, de Vroey G. Recommendations for health monitoring of mouse, rat, hamster, guineapig, and rabbit breeding colonies. Report of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Animal Health accepted by the FELASA Board of Management November 1992. Lab Anim 1994, 28:1–12.
6 . Rehbinder C, Baneux P, Forbes D, van Herck H, Nicklas W, Rugaya Z, Winkler G. FELASA recommendations for the health monitoring of breeding colonies and experimental units of cats, dogs, and pigs. Report of the Federation of European Laboratory Animal Science Associations Working Group on Animal Health. Lab Anim 1998, 32:1–17.
7 . Rehbinder C, lenius S, Bures J, de las Heras ML, Greko C, Kroon PS, Gutzwiller A. FELASA recommendations for the health monitoring of experimental units of calves, sheep, and goats. Report of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Animal Health. Lab Anim 2000, 34:329–350.
8 . Nicklas W, Baneux P, Boot R, Decelle T, Deeny A, Fumanelli M, Illgen-Wilcke B. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Recommendations of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Health Monitoring of Rodent and Rabbit Colonies accepted by the FELASA Board of Management, 9 June 2001. Lab Anim 2002, 36:20–42.
9 . ICLAS (International Council for Laboratory Animal Science). Performance Evaluation Program for Diagnostic Laboratories (PEP). ICLAS Network for Promotion of Animal Quality in Research. 2007. Available online at http://www.iclas.org/NetworkPEP.htm
10 . Guillen J. FELASA guidelines and recommendations. J Am Assoc Lab Anim Sci. 2012, 51:311-21.
11 . Nicklas W. International harmonization of health monitoring. ILAR J. 2008; 49(3):338-46.
1 SIAL (Servicios Integrados del Animal de Laboratorio)
Department of Cellular Biology – Physiology and Immunology Faculty of Veterinary - Universidad Autónoma de Barcelona
08193 - Bellaterra (Barcelona), Spain.
Tel +34 93 581 4781
MariaAsuncion.Romero@uab.cat