Ten years-long survey on pathogen status of mouse and rat breeding colonies

Eleven pathogens including P. aeruginosa, Salmonella spp., E. coli O115a, c: K(B), P. pneumotropica, B. bronchiseptica, C. kutscheri, Tyzzer's organism, M. pulmonis, Sendai virus, MHV and Syphacia spp. were surveyed in 217 mouse and rat breeding colonies during 1972-1981. In conventional animals, P. pneumotropica and/or Syphacia spp. were detected in nearly 90% of 89 mouse and 64 rat colonies. Sendai virus, M. pulmonis, P. aeruginosa and MHV were positive in 51.7 to 23.6% of the colonies, and Tyzzer's organism, B. bronchiseptica and probably SDA virus were also detected in more than 10% of the rat colonies. Salmonella spp., E. coli O115a, c: K(B) and C. kutscheri were found in a few colonies. In SPF animals, P. aeruginosa was isolated from about one third of 33 mouse and 31 rat colonies, and P. aeruginosa was isolated from about one third of 33 mouse and 31 rat colonies, and P. pneumotropica was also positive in 3 rat colonies. Infection rates of P. pneumotropica, M. pulmonis, Sendai virus and Syphacia spp. were usually higher than 40% of animals sampled from colonies contaminated with them. Accidental contaminations of SPF colonies were usually caused by P. pneumotropica and Syphacia spp.     

A serological survey on 15 murine pathogens in mice and rats

A serological survey for 15 murine pathogens was performed on 269 mouse sera collected from 21 conventional and 12 barrier colonies, and on 376 rat sera collected from 21 conventional and 23 barrier colonies. Animals having an antibody against at least one of the antigens were contained in 81.0% of conventional and 16.7% of barrier mouse colonies and also in 81.0% of conventional and 43.5% of barrier rat colonies. Main contaminants were mouse hepatitis virus and Sendai virus in mice, and Sendai virus and pneumonia virus of mice in rats. Results also indicated that antibodies to Toolan's H-1, minute virus of mice and PVM were positive in mice from a considerable number of colonies and those to Kilham rat virus, Mycoplasma pulmonis and Toolan's H-1 were sometimes detected in rats, suggesting prevalences of these pathogens in mice and rats in Japan.     

Intestinal parasites of conventionally maintained BALB/c mice and Mastomys coucha and the effects of a concomitant schistosome infection

A longitudinal study was carried out to identify the spectrum of intestinal parasites present in conventionally maintained BALB/c mice and Mastomys coucha and to determine the effects of concomitant schistosome infections on their parasite status. Six parasites were observed during the course of the study, namely the nematodes Aspiculuris tetraptera and Syphacia obvelata, Entamoeba muris and the flagellates Trichomonas muris, Spironucleus muris and Chilomastix spp. Although the 2 rodents shared common facilities, the overall prevalences of S. obvelata, T. muris and S. muris were significantly higher in M. coucha than BALB/c mice. BALB/c mice with concomitant schistosome infection had increased prevalences of E. muris, T. muris and S. muris. In M. coucha, in contrast, there were no significant increases in parasite prevalences. Infection intensities of T. muris and S. muris were significantly greater in M. coucha than BALB/c mice. Concomitant schistosome infection resulted in increased intensities of T. muris infection in BALB/c mice only. The influence of immune status in determining the susceptibilities of rodents to environmentally transmitted parasites is discussed.     

Microbiological contamination of laboratory mice and rats in Korea from 1999 to 2003.

To survey the microbiological contamination of laboratory mice and rats in Korea during a 5-year period, we monitored animals housed in mouse and rat facilities with either barrier or conventional systems. At barrier and conventional mouse facilities, the most important pathogen identified was mouse hepatitis virus (MHV), while Mycoplasma pulmonis was the most important pathogen at conventional rat facilities. Interestingly, hantavirus was recovered from both barrier and conventional mouse facilities. The most common protozoon identified was Tritrichomonas muris in mouse facilities and Entamoeba muris in rat facilities. In addition, we found that the microbiological contamination of mice and rats in conventional facilities was severe. These results suggest that conventional facilities should be renovated and monitored regularly to decrease microbiological contamination. We also propose that hantavirus should be monitored in Korea as an important mouse pathogen.     

Ten-year long monitoring of laboratory mouse and rat colonies in French facilities: a retrospective study

From 1988 to 1997, a total of 69 mouse colonies and 36 rat colonies were examined for the presence of antibodies to 14 indigenous viruses of mice and rats. Among mouse viruses, high positivity rates were observed with mouse hepatitis virus (MHV), Theiler's encephalomyelitis virus (THEMV), minute virus of mice (MVM), Sendai virus and pneumonia virus of mice (PVM); the prevalence rates were high in rats with Khilam's rat virus (KRV), THEMV, Toolan's H-1 virus, Sendai virus, Parker's rat coronavirus (RCV/SDA) and PVM. During the last decade, the prevalence of some agents such as MHV, Sendai virus, THEMV, PVM and MVM has apparently decreased although they were still present in 1997 (except for PVM). Another point is the constant increase of colonies found free of viruses through this decade, demonstrating the efforts of the French research community to increase the quality of hygiene in laboratory animals.     

Efficacy of three microbiological monitoring methods in a ventilated cage rack

The use of individually ventilated caging (IVC) to house mice presents new challenges for effective microbiological monitoring. Methods that exploit the characteristics of IVC have been developed, but to the authors' knowledge, their efficacy has not been systematically investigated. Air exhausted from the IVC rack can be monitored, using sentinels housed in cages that receive rack exhaust air as their supply air, or using filters placed on the exhaust air port. To aid laboratory animal personnel in making informed decisions about effective methods for microbiological monitoring of mice in IVC, the efficacy of air monitoring methods was compared with that of contact and soiled bedding sentinel monitoring. Mice were infected with mouse hepatitis virus (MHV), mouse parvovirus (MPV), murine rotavirus (agent of epizootic diarrhea of mice [EDIM]), Sendai virus (SV), or Helicobacter spp. All agents were detected using contact sentinels. Mouse hepatitis virus was effectively detected in air and soiled bedding sentinels, and SV was detected in air sentinels only. Mouse parvovirus and Helicobacter spp. were transmitted in soiled bedding, but the efficacy of transfer was dependent on the frequency and dilution of soiled bedding transferred. Results were similar when the IVC rack was operated under positive or negative air pressure. Filters were more effective at detecting MHV and SV than they were at detecting MPV. Exposure of sentinels or filters to exhaust air was effective at detecting several infectious agents, and use of these methods could increase the efficacy of microbiological monitoring programs, especially if used with soiled bedding sentinels. In contemporary mouse colonies, a multi-faceted approach to microbiological monitoring is recommended.     

Long-term population dynamics of pinworms (Syphacia obvelata and Aspiculuris tetraptera) in mice

The population dynamics of concurrent infections of Syphacia obvelata and Aspiculuris tetraptera (Nematoda) in laboratory mice were investigated under conditions of constant re-exposure over periods of 56 and 115 days. The results indicate that A. tetraptera burdens equilibrate at a higher level than S. obvelata burdens and that both parasites become aggregated in the mouse population. Parasite burdens were higher following short-term (7 day) exposure of uninfected tracer mice to both parasites when compared with parasite burdens attained over long-term exposure, indicating probable development of immunity. A significant positive correlation was detected between numbers of immature S. obvelata and immature A. tetraptera for both experimental and tracer mice.     

A retrospective study of the microbiological and parasitological status of laboratory rodents in France

Between 1988 and 1997, 72 mouse colonies and 38 rat colonies were examined for the presence of bacteria parasite infections. Among mouse and rat bacteria, high positive rates were observed with Proteus species (sp.), Pasteurella pneumotropica, Mycoplasma sp. and Pseudomonas aeruginosa. Concerning murine colonies, parasites frequently detected were Tritrichomonas sp., Syphacia sp., Aspiculuris tetraptera, Entamoeba muris, Spironucleus muris, Myobia musculi, Chilomastix sp. and Myocoptes musculinus. In rats, high rates were obtained with Syphacia sp., Tritrichomonas sp., Spironucleus muris, Entamoeba muris and Chilomastix sp. During the first part of the last decade, some agents such as Clostridium piliforme, Citrobacter sp., Mycoplasma sp., Pseudomonas aeruginosa, Myobia musculi, Radfordia ensifera, Spironucleus muris and Giardia muris were often found among rodents, and most of them were still present in 1997. At the time of our study, results point out that some agents are still persistent, even increasing during the same period. It is particularly the case for parasites such as Entamoeba muris and the oxyurids, but also for bacteria like Proteus sp. and Klebsiella pneumoniae. We can thus conclude that only very limited success has been achieved in preventing microbial and parasitic infections in mice and rats colonies.     

Alteration of viral respiratory infections of mice by prior infection with mouse hepatitis virus

Pre-infection with mouse hepatitis virus (MHV) strains S, 3, or JHM reduced the ability of mice to seroconvert to PVM. Geometric mean antibody titers to PVM among MHV pre-infected mice were lower than those for control mice given only PVM, and dually infected mice seroconverted to PVM later than mice given PVM alone. PVM was not recovered from normally permissive respiratory tract tissues of MHV-S pre-infected mice. Pre-infection of DBA/2 mice with MHV-S compromised the susceptibility of these mice to lethal Sendai virus infection but did not substantially reduce the titers of infectious Sendai virus recovered from the lungs. Serologic responses to Sendai virus and lung Sendai virus titers were similar in Sendai virus-resistant C57BL/6 mice pre-infected or not with MHV-S.     

Serological examinations on natural infections with mouse pathogens in inbred mouse strains: difference in antibody detection among the strains (author's transl)

Serological surveys on several infections were performed on the inbred mouse strains maintained at the Central Institute for Experimental Animals. In the first survey, 11 strains of mouse, which were 8 weeks of age or older and were kept in separate cages in the same animal room, were tested for antibodies to Salmonella enteritidis, Corynebacterium kutscheri, Tyzzer's organisms, Mycoplasma pulmonis, mouse hepatitis virus (MHV), Sendai virus (HVJ), pneumonia virus of mice (PVM) and minute virus of mice (MVM). Positive results were obtained in MHV, HVJ, PVM and MVM. Positive rates for these viruses except for MVM were different among mouse strains. In the second survey, 5 strains of mouse kept together in the same cage for 4 weeks after weaning were examined for MHV and HVJ antibodies. Positive rates to MHV were different among mouse strains as observed in the first survey. For HVJ antibody, no difference was demonstrated in positive rates unlike in the first survey, but the titers varied between the strains. These results suggest the difference in antibody response to natural infections dependent on mouse strains.     

An attempt for eradication of respiratory diseases in breeding mice by sanitary improvement of care

An attempt was made to eradicate respiratory diseases developed in about 1,000 mice of 19 congenic inbred strains which were maintained in a mouse breeding room. The contagious diseases with respiratory signs were found to be caused by mixed infections with Mycoplasma pulmonis and Sendai virus. The eradication of the diseases was mainly made by sanitary improvement in care of the mice such as intensive disinfection, culling some diseased mice and so on, instead of destroying all colonies. As the result, mycoplasma infection decreased gradually, resulting in a complete eradication about one and half years later and remarkable increases in litter size and weaning rate of mice were obtained. Sendai virus infection failed to be eradicated.     

Distribution of Pseudomonas aeruginosa in experimentally infected mice (author's transl)]

The distribution of experimentally administered Pseudomonas aeruginosa was studied in germfree CF no. 1 mice, barrier-sustained DDD mice with or without oral treatment of aminobenzyl-penicillin and conventional DDD mice. On day 1 after oral administration of 8 X 10(7) organisms, more than 10(8) of organisms/g were recovered from the feces of ex-germfree mice and the number was maintained during the experiment. On the other hand, from barrier-sustained mice with antibiotic treatment and those without the treatment, 10(4-7) and 10(3) organisms were recovered, respectively. In all of monoassociated mice and some antibiotic-treated barrier-sustained ones the organisms were recovered also from the lungs, liver, spleen and kidneys. In conventional mice, however, no organisms were recovered from the internal organs throughout the experiment, while some were detectable from the intestinal tracts. The distribution of the organisms in naturally infected mice appears to be similar to that of experimentally infected animals with antibiotics.     

Seromonitoring of laboratory mouse and rat colonies for common murine pathogens (author's transl)]

During a period from 1973 to 1978, 392 and 225 lots including 12,232 mouse and 8,044 rat individual sera, respectively, were examined for antibodies to murine hepatitis virus, Sendai virus, Bordetella bronchiseptica, Mycoplasma pulmonis, Tyzzer agents, Salmonella typhimurium and Corynebacterium kutscheri. Of mouse lots 94.5% and 39.3% from breeder and user colonies, respectively, were negative for all antibodies examined as well as 31.6% and 17.2% of rat breeder and user colonies, respectively. Among positive lots from mouse users, high positivity rates were seen with Senai virus (47.6%), M. pulmonis (19.0%), and murine hepatitis virus (JHM : 18.2%, MHV : 31.0%), while the rates were high in rat user lots with Sendai virus (24.4%), B. bronchiseptica (39.3%) M. pulmonis (12.5%), murine coronaviruses (JHM : 19.0%, MHV-2 : 28.0%) and tyzzer agents (MSK : 19.6%, RT : 17.9%). These pathogenes with high positivities should be monitored indispensably as a quality control of laboratory mice and rats.     

Microbiological monitoring of laboratory mice and biocontainment in individually ventilated cages: a field study

Over recent years, the use of individually ventilated cage (IVC) rack systems in laboratory rodent facilities has increased. Since every cage in an IVC rack may be assumed to be a separate microbiological unit, comprehensive microbiological monitoring of animals kept in IVCs has become a challenging task, which may be addressed by the appropriate use of sentinel mice. Traditionally, these sentinels have been exposed to soiled bedding but more recently, the concept of exposure to exhaust air has been considered. The work reported here was aimed firstly at testing the efficiency of a sentinel-based microbiological monitoring programme under field conditions in a quarantine unit and in a multi-user unit with frequent imports of mouse colonies from various sources. Secondly, it was aimed at determining biocontainment of naturally infected mice kept in an IVC rack, which included breeding of the mice. Sentinels were exposed both to soiled bedding and to exhaust air. The mice which were used in the study carried prevalent infectious agents encountered in research animal facilities including mouse hepatitis virus (MHV), mouse parvovirus (MPV), intestinal flagellates and pinworms. Our data indicate that the sentinel-based health monitoring programme allowed rapid detection of MHV, intestinal flagellates and pinworms investigated by a combination of soiled bedding and exhaust air exposure. MHV was also detected by exposure to exhaust air only. The IVC rack used in this study provided biocontainment when infected mice were kept together with non-infected mice in separate cages in the same IVC rack.     

Rederivation of inbred strains of mice by means of embryo transfer

Embryo transfers were performed to rederive six inbred strains of mice, A/He, BALB/cByJ, BALB/c Lac, B10.BR/SgSnJ, C57BL/6J and DBA/2J. The aim was to determine whether it is possible to eliminate pathogens like mouse hepatitis virus (MHV) and Pasteurella pneumotropica (P.p.). The embryos were collected, handled and transferred into the oviduct of day one pseudopregnant SPF surrogate mothers under aseptic conditions. In 40.5% of the transfers, embryos developed to term. With respect to surrogate mothers delivering viable litters, 47.9% of the transferred embryos were born alive. Out of these 93.5% were reared. Virological and bacteriological examination of embryo donors verified the presence of P.p. and of antibodies against MHV in all strains. In some embryo donors P.p. could be isolated even from the uterine mucosa. However, neither in the surrogate mothers nor in the offspring could P.p. and antibodies against MHV be detected. Further bacteriological examination revealed that the offspring carried only the microbial flora received from the surrogate mother. The results indicate that embryo transfer is an appropriate tool to rederive mouse strains. In contrast to hysterectomy rederivation, embryo transfer has the advantage of avoiding postimplantational vertical transmissions of infections.     

Diagnosis of murine infections in relation to test methods employed

Comparative investigations of Sendai virus, pneumonia virus of mice (PVM), mouse encephalomyelitis virus (mouse polio), minute virus of mice (MVM), and reovirus type 3 (Reo 3) infected murine colonies revealed a 30% higher incidence of positive sera when enzyme-linked immunosorbent assay (ELISA) was employed instead of hemagglutination inhibition (HI) tests. Equivalent sensitivity as in the ELISA was obtained when the same sera were investigated by indirect immunofluorescence (IF) tests. The virus purification techniques described resulted in highly suitable antigens for all indirect ELISA established. Since IIF requires no purified antigens, this test is recommended as an alternative to ELISA as well as to HI and complement fixation (CF) tests for laboratories lacking the necessary equipment for high speed centrifugation. A high incidence of false positive HI reactions was found particularly in Reo 3 routine serology. An updated survey of seromonitoring showed that European murine colonies appeared to be infected far less with Reo 3 if ELISA or IIF tests were employed. During 1982-1984, only 13% of the mouse colonies screened possessed Reo 3 positive sera whereas no natural Reo 3 infection was found in rat colonies. Mouse hepatitis virus (MHV) and the coronaviruses of rats exhibited the highest incidence in murine colonies. A total of 60% of mouse and 41% of rat colonies were found to be infected by these viruses. In comparison with earlier serological surveys, the relative incidence of other murine infections was similar. Antibodies against Bacillus piliformis (Tyzzer's disease) were detected by the IIF test in 41% of the rat colonies screened.     

Studies on the development of an ELISA kit for microbiological monitoring. 1. Evaluation of the reliability of the prototype kit by field tests

The prototype of an ELISA kit using protein A as the second reaction reagent for mice and anti-rat IgG for rats was prepared for seromonitoring of the Sendai virus and mouse hepatitis virus (MHV)/sialodacryoadenitis virus (SDAV)/Parker's rat coronavirus (PCV) infections. The respective antigen strains and protein concentrations were Sendai virus MN strain, 2 micrograms/ml and MHV Nu-67 strain, 5 micrograms/ml. The reliability of this prototype kit was investigated in two field tests performed on a total of 10,094 mouse and rat sera from 147 institutions. The results indicated that the two types of kits for the two species of animals were highly specific, but it is necessary to increase the detection sensitivity of the MHV antigen for the MHV antibody of mice and SDAV/PCV antibodies of rats.     

Patterns of infection with the nematodes Syphacia obvelata and Aspiculuris tetraptera in conventionally maintained laboratory mice

Data on the frequency, distribution and mean intensity of the helminth fauna recovered from outbred and inbred mice conventionally maintained in Brazilian animal houses, are reported. The oxyurid nematodes Syphacia obvelata and Aspiculuris tetraptera presented overall frequencies of 91.5% and 8.5%, respectively. The frequency of S. obvelata in animals of three groups out of the four investigated ranged from 9% to 74% and A. tetraptera from 17% to 83%, since animals of one of the groups were negative for helminths. Infections due to a single species were observed in 62% of the animals, compared to 16% related to associations. The frequency of single infections in each group varied from 58.6% to 100% whereas associations varied from 24.1% to 41.4%. The analysis of specific mean intensities showed that S. obvelata was represented by 13.35 to 66.58 specimens/host and A. tetraptera by 5.85 to 16.75 specimens/host.     

A survey of rodent-borne pathogens carried by wild-caught Norway rats: a potential threat to laboratory rodent colonies

Unintentional infection of laboratory rodents can compromise scientific research as well as the health of the animals and animal handlers. The source of contamination often is unknown, but may be introduced by wild rats from surrounding environments. To determine whether rats in Baltimore, Maryland, USA carry infectious agents commonly found in laboratory rodent colonies, we live-trapped 162 rats during 2005 to 2006 and screened them for a panel of viruses, bacteria and parasites. Antibodies against rat coronavirus/sialodacryoadenitis virus (91.7%), Mycoplasma pulmonis (72.9%), cilia-associated respiratory bacillus (52.1%), rat parvovirus/rat minute virus (29.2%), Kilham rat virus (10.4%), Toolan's H-1 virus (10.4%), Sendai virus (4.2%) and Theiler's mouse encephalomyelitis virus (4.2%), were detected in wild-caught Norway rats. Antibodies against reovirus and pneumonia virus of mice were not detected in wild Norway rats. Endoparasites, including Nippostrongylus braziliensis (71.6%), Rodentolepis nana or Hymenolepis diminuta (34.4%), Hetarakis spumosa (24.1%) and Trichuris muris (14.8%), as well as ectoparasites (14.8%), were identified in wild-caught rats. The risk of pathogen transmission from wild-caught rats to laboratory colonies needs to be mitigated by minimizing exposures rather than assuming wild animals represent a minimal hazard.     

Infectious Diseases in Wild Mice (Mus musculus) Collected on and around the University of Pennsylvania (Philadelphia) Campus

Laboratory mice serve as important models in biomedical research. Monitoring these animals for infections and infestations and excluding causative agents requires extensive resources. Despite advancements in detection and exclusion over the last several years, these activities remain challenging for many institutions. The infections and infestations present in laboratory mouse colonies are well documented, but their mode of introduction is not always known. One possibility is that wild rodents living near vivaria somehow transmit infections to and between the colonies. This study was undertaken to determine what infectious agents the wild mice on the University of Pennsylvania (Philadelphia) campus were carrying. Wild mice were trapped and evaluated for parasites, viruses, and selected bacteria by using histopathology, serology, and PCR-based assays. Results were compared with known infectious agents historically circulating in the vivaria housing mice on campus and were generally different. Although the ectoparasitic burdens found on the 2 populations were similar, the wild mice had a much lower incidence of endoparasites (most notably pinworms). The seroprevalence of some viral infections was also different, with a low prevalence of mouse hepatitis virus among wild mice. Wild mice had a high prevalence of murine cytomegalovirus, an agent now thought to be confined to wild mouse populations. Helicobacter DNA was amplified from more than 90% of the wild mice (59% positive for H. hepaticus). Given the results of this study, we conclude that wild mice likely are not a source of infection for many of the agents that are detected in laboratory mouse colonies at the University of Pennsylvania.Abbreviations: EDIM, epizootic diarrhea of infant mice; MAV, mouse adenovirus; MCMV, murine cytomegalovirus; MFIA, multiplex fluorescent immunoassay; MHV, mouse hepatitis virus; MNV, murine norovirus; MPV, mouse parvovirus; MVM, minute virus of mice; TMEV, Theiler mouse encephalomyelitis virusLaboratory mice constitute the most popular animal models used in biomedical research today. Like all animals, even mice housed in so-called ‘barrier’ facilities are subject to infection. The infectious agents and organisms present in laboratory mouse colonies on the University of Pennsylvania campus are known and documented by the University Laboratory Animal Resources Diagnostic Services Unit. Sentinel mice that are housed on soiled bedding from resident mouse cages are screened onsite at 3 quarterly intervals for fur mites and pinworms and for a panel of viral infections: mouse hepatitis virus (MHV); epizootic diarrhea of infant mice (EDIM) virus; minute virus of mice (MVM); mouse parvovirus (MPV); Theiler mouse encephalomyelitis virus (TMEV); and Sendai virus. Comprehensive bacteriology and parasitology assessments are performed on all sentinels once yearly during the fourth quarter. In addition, these sentinels are screened serologically for 18 viral infections, Mycoplasma pulmonis, cilia-associated respiratory bacillus, and Encephalitozoon cuniculi and by PCR for Helicobacter spp. and M. pulmonis. Mesenteric lymph nodes from sentinels monitoring barrier-maintained colonies are also screened once yearly by PCR for MPV. In addition, University Laboratory Animal Resources maintains a quarantine facility for rodents received from nonapproved sources (sources other than selected commercial breeding facilities). Mice entering the quarantine facility are housed in semirigid isolators, and contact sentinels are tested for all of the agents included in the fourth quarter comprehensive health assessment described, including PCR for MPV.Wild mice (Mus musculus) could serve as a source of infection or infestation in laboratory mouse colonies, although little is known about the prevalence of infectious diseases in wild mouse populations in Philadelphia. However, we have surveyed wild mouse populations in other geographic areas.^1,9 Significant seroprevalence of MHV, EDIM, murine cytomegalovirus (MCMV), parvovirus, and thymic virus (murid herpesvirus 3), in addition to the presence of many types of parasites and bacteria including Myocoptes spp., Myobia spp., Radfordia spp., Spironucleus spp., Giardia spp., Pasteurella pneumotropica, Pseudomonas spp., and Leptospira spp. were found in wild populations of mice from farms in southeastern Connecticut.¹ Studies of wild mouse (Mus domesticus) populations in the cereal-growing region of southeastern Australia revealed a high serologic prevalence of MHV, EDIM, and MCMV, as well as significant seroprevalence of mouse adenovirus (MAV), MPV, and reovirus type 3.⁹The goal of the current study was to expand preliminary data obtained from wild mice trapped in the University City district of Philadelphia in 2005 (which are included with the current results from a 2007 survey). These data document the prevalence of various infectious agents and parasites commonly found in populations of wild mice on the University of Pennsylvania campus in Philadelphia and are discussed in the context of infectious disease outbreaks in campus vivaria over the past 5 y.