Natural infections of guinea-pigs

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1976 10: 119Lab AnimCharlotte Rigby

Natural infections of guinea-pigs

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Laboratory Allimals (1976) 10, 119-142.

NATURAL INFECTIONS OF GUINEA-PIGSby

CHARLOTTE RIGBY*

Department of Veterinary Microbiology,

Western College of Veterinary Medicine,

University of Saskatchewan, Saskatoon, Saskatchewan S7NOWO,Canada

119

The guinea-pig (Cavia porcellus) is an important laboratory animalwhose susceptibility to a wide range of pathogens has made it extremely use-ful in research and diagnosis. In the United States about 600000 guinea-pigs are used each year; only mice and rats are more common (ILAR, 1972).

Guinea-pigs are thought to have originated in the mountains of Peru, andlittle is known about the diseases which they suffer in their natural habitat.In the artificial environment of the animal colony a number of infectiousagents may cause disease problems. These are most likely to occur whenthe animals are under stress because of overcrowding, a breakdown in sani-tation, or abrupt changes in temperature, humidity, or diet. Such infectionsmay be either sporadic or epizootic, and often produce a high mortality. Inthis discussion, they are grouped under the heading 'spontaneous infectiousdiseases'. Most of the agents involved have been isolated and well-character-ized, and methods have been devised for their control. With careful manage-ment, including routine surveillance to detect and eliminate infected animals,they need not cause many serious problems. Good management practiceshave been described (for example, Lane-Petter & Pearson, ]971; UFAW,1972) and will not be repeated here. BasicalIy they consist of common sense;if an infectious disease does cause losses, most often it is due to a lapse ofattention to the management routine.

Inapparent infections pose a different type of problem. In these cases abalanced relationship exists between parasite and host: the infected hostremains healthy and the pathogen is almost always undetected. However,when stress such as experimental infection disturbs this balance, the pathogenmay multiply or exert its effects. Infected animals may respond unpredict-ably to experimental treatments, yielding inconclusive or misleading results.In recent years the increased recognition of the importance of healthy animalsfor diagnosis and research has stimulated progress in identifying and charac-terizing such infettions (Baker, Cassell & Lindsey, 1971; Irving, 1972).

·Present address: Animal Diseases Research Institute (E), P.O. Box 11300, Postal StationH, Ottawa, Ontario K2H 8P9, Canada.

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120 C. RIGBY

Further knowledge of their pathogenesis seems likely, in some cases at least,to reveal similarities to human diseases which could make them extremelyuseful animal models for research into human infections.

This paper will first of all review the better-known spontaneous infectiousdiseases causing losses in guinea-pig colonies. Secondly, it will discuss someexamples of inapparent infections which may be important because of their(often unrecognized) deleterious effects on experimental results, or because oftheir possible relationships to human diseases.

SPONTANEOUS INFECTIOUS DISEASES

It is difficult to estimate the incidence of diseases in laboratory animals,or their economic impact on diagnostic and research funds. In Britain,Seamer & Chesterman (1967) conducted a survey to identify the most commondisease problems in laboratory animals. They sent a questionnaire to 46institutions; 33 responded, representing a total of almost 3000 OOOanimals,including 161 620 guinea-pigs. The problems considered by the respondentsto be important in guinea-pigs included: respiratory problems (11 laboratories);'pasteurellosis'-presumably Yersinia pseudotuberculosis infection (8); septicinfections (5); otitis media (5); enteritis (5); coccidiosis (3); urinary tractdisease (3); skin and eye disease (3); genital infections (2); mastitis (2); sal-monellosis (2); lice (2); helminth infestation (1); and staphylococcal infection(1). 'Undiagnosed disease' was indicated as a major problem by 14 insti-tutions. Only 20 laboratories routinely necropsied dead or culled animals.The authors felt that the responses, besides identifying the more commoninfectious disease problems, also indicated serious deficiencies in routinediagnosis and record-keeping facilities in animal colonies.

In our own institution, we reviewed the routine necropsy records of guinea-pigs which died or were culled from a conventional, closed breeding colony(consisting usually of between 300 and 400 animals) in the Animal ResourcesCentre of the University during the period July 1971 to September 1974. Theprincipal findings or presumed cause of death were classified as shown inTable 1. Of 88 guinea-pigs necropsied, 70 (80 %) presumably suffered in-fection of some kind. Pneumonia was by far the most common problem(39 animals) and Diplococcus pneumoniae the most common pathogen (17isolates).

During this period an outbreak of Salmonella typhimurium infection occurred(Olfert, Ward & Stevenson, 1976). The animals affected or killed during thisepizootic have not been included in Table 1.

Table 2 lists some of the more common infectious disease problems ofconventional guinea-pig colonies, and includes their associated aetiologicalagents, common sources of infection, and methods for their diagnosis andcontrol.




NATURAL INFECTIONS OF GUINEA-PIGS 121

Table 1. Principal findings at necropsy of 88 guinea-pigs which died or were culledfrom the Animal Resources Centre, University of Saskatchewan, guinea-pig colony

from July 1971 to September 1974.

Infectiousfindings and no. animals

Pneumonia'" 39Lymphadenitis and abscessest 7Enteritis 5Dermatomycosis 4Peritonitis 4Metritis 3Otitis media 2Nephritis 2Septicaemia 2Myositis 1

70 (80%)

Non-infectiousfindingsandno.anima~

Malocclusion 4Pregnancy difficulties 3Pregnancy toxaemia 2Alopaecia 2Nutritional deficiencies 2Congenital abnormalities 2Tumour 1LeuJcaemia 1Undiagnosed 1

18 (20%)

'"Diplococcus pneumonia was cultured from ]6, Pasteurella hemolytica from 1.tStreptococcus zooepidemiclls was cultured from ], Diplococcus pneumoniae from 1.

Bacteria

Bacterial infections are by far the most common and serious of the diseasesaffecting laboratory animal colonies. Without exception, diagnosis dependson the isolation and identification of the causal agent. For the necessarybacteriological techniques interested readers are referred to such excellentmanuals as those of Osbaldiston (1973) and Carter (1973).

The nomenclature of many important bacterial pathogens is still unsettled;we follow that given in Bergey's manual of determinative bacteriology (Buchanan& Gibbons, 1974).

Bordetella

Bordetella bronchiseptica is probably the most common cause of acutepneumonia in the guinea-pig (Neil, 1972). Subclinical infection is common,and the organism may easily be cultured from the nares and trachea of normalanimals. Of 120 healthy guinea-pigs examined by Yoda, Nakagawa, Muto& Imazumi (1972), 119 carried B. bronchiseptica in the nasal cavity for amonth or longer. Acute pneumonia may result when this 'normal' host-parasite relationship is disturbed. In one such epizootic, in which 19 % ofthe colony's adult breeders died (Woode & McLeod, ] 967), the affected animalsrarely showed any clinical signs before death. At necropsy, an extensivebronchopneumonia with a reddish-brown pleuritic exudate was the principal




122 C. RIGBY

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124 C. RIGBY

finding. In all cases, cultures of affected lung tissue yielded a pure growthof B. bronchiseptica. The epizootic was finally controlled by identifying andsacrificing all nasal carriers and their contacts, then thoroughly disinfectingtheir quarters.

Autologous vaccines have been used to control similar epizootics withencouraging results (Ganaway, Allen & McPherson, 1965; Nikkels & Mullink,1971; Nakagawa, Yoda, Muto & Imazumi, 1974). Rabbits and rats alsofrequently carry B. bronchiseptica in the upper respiratory tract, and cross-infection may occur-a reason for housing different species of animals inseparate rooms.

SalmonellaSalmonellosis is a serious threat to laboratory animals and to their human

attendants. Both chronic and acute salmonellosis occur as epizootics inanimal colonies; both are a hazard to human health.

In the early stages of an outbreak of acute salmonellosis due to Salmonellaenteritidis, which occurred in a lOOO-animal commercial guinea-pig colony,only a few animals succumbed after a brief, acute illness or severe diarrhoea(Fish, Fletch & Butler, 1968). After a month losses suddenly increased tomore than 20 animals a day. Gravid sows showing signs of infection had anabortion rate of 60 %. S. enteritidis was cultured from the tissues of deadanimals; and treatment with sulphamethazine, neomycin, and nitrofurazoneattempted, unsuccessfully. After 2 months over 500 animals had died and,during this time, 3 human cases of salmonellosis were traced to this outbreak.The disease was finally c~:mtrolled by depopulating the colony.

In such acute outbreaks death may occur in a few hours, preceded only byroughening of the fur, weakness, and mild diarrhoea. Few changes (possiblyonly a slightly enlarged spleen) are seen at necropsy. It is important to culturethe organism from affected tissues in order to differentiate salmonellosis fromother acute septicaemias. This is best accomplished by the inoculation ofspecimens into an enrichment medium (such as selenite or tetrathionate broth)in addition to routine bacteriological media.

Chronic salmonellosis causes a general wasting of the affected animals, withdeath occurring after several weeks. At necropsy, the spleen, liver and lymphnodes are enlarged, an ulcerative enteritis is common, and a peritonitis maybe present. As in acute salmonellosis, the chronic form is diagnosed byisolating the organism from affected viscera.

Several species of Salmonella have been incriminated in epizootic guinea-pigsalmonellosis, including the common animal types S. enteritidis, S. dublin, S.florida, S. poona, and S. bredeney (Haberman & Williams, 1958a; Neil, 1972).Wild rodents, newly-introduced stock, and contaminated food are frequentsources of infection. Animals which recover may remain chronic faecal





excretors of the organism so that control necessitates prompt removal of allaffected animals and their contacts, followed by disinfection of their quarters.These measures, combined with regular surveillance of the colony by culturalexamination of pooled faecal samples, are an effective means of control (Olfertet al., ]976).

In an unusual type of salmonellosis, presenting as a mesenteric lympha-denitis with no visible systemic effects (Paterson & Cook, 1955), S. limete(Salmonella group B) was isolated from the infected lymph nodes. It wasnot pathogenic for mice, and affected guinea-pigs were still very susceptibleto infection with S. typhimurium, another member of Salmonella group B.The prevalence of such infection by S. limete in guinea-pig colonies is un-known.

Yersinia

Yersinia pseudotuberculosis, a common pathogen of rodents, produces 3distinct syndromes in guinea-pigs (Paterson, 1972). Most common is 'classical'pseudotuberculosis, with chronic caseous lesions in mesenteric and coloniclymph nodes. Lymphadenitis, emaciation and diarrhoea are seen; deathoccurs after several weeks. Newborns may be infected, either congenitally,or soon after birth. At necropsy the principal findings are enlarged, caseouslymph nodes, and focal necrosis in the liver and spleen.

A second form is an acute septicaemic pneumonia. Coughing and rapidbreathing, with death in 24 hours, are the principal signs. Severely congestedlungs are seen at necropsy.

Thirdly, Y. pseudotuberculosis may cause a chronic cervical lymphadenitis,with the animals remaining in good condition. The danger of this infectionis that the lesions may burst externally, disseminating the organism and spread-ing the infection.

The organism is readily isolated from the tissues and faeces of infectedanimals. Wild birds and rodents are frequent sources of infection. InBritain, pigeon faeces contaminating greens introduced the organism into aguinea-pig colony (Paterson & Cook, ]963).

An effective control method consists of regular palpation for enlargedmesenteric and colonic lymph nodes (Paterson, ]972). In this way, animalsin the early stages of infection may be detected and destroyed before they beginto excrete the organism in faeces.

Strep tobacill us-Fusobac terium

Streptobacillus moniliformis, a common commensal of the throat of rats,is said to be a rare cause of cervical lymphadenitis in the guinea-pig (ILAR,1974). The organism is an aerobic, pleomorphic Gram-negative bacillus.




126 C. RIGBY

Since it is difficult to isolate, an aetiological diagnosis has often been madewhen such organisms are seen in Gram-stained smears of pus.

The situation is, however, rather confusing. Guinea-pig strains of S.moniliformis differ from strains isolated from rats in that they require anaero-biosis for isolation and are rather inert biochemically (Aldred, Hill & Young,1974). We have also isolated such strains in our laboratory, and we considerthat they conform more closely to the published descriptions of Fusobacteriumnecrophorum (formerly Spherophorus necrophorus) (Buchanan & Gibbons, ]974).It would be of interest to characterize such strains further, particularly sinceguinea-pig lymphadenitis, if it is truly caused by F. necrophorum, could proveto be a useful model for the study of infections due to this organism in largeranimals and man.

KlebsiellaKlebsiella pneumoniae, a relatively non-pathogenic organism which is widely

distributed in nature, may cause a highly contagious, fatal pneumonia inguinea-pigs which are debilitated by sudden changes in diet or environment,or by experimental manipulation (Paterson, ]972). Emaciation, labouredbreathing, and purulent nasal discharge are followed by rapid death. Apurulent bronchopneumonia is seen at autopsy, and the organism is easilyrecovered from affected tissues.

Pseudomonas

Pseudomonas aeruginosa is a ubiquitous, usually non-pathogenic organismwhich may be introduced into laboratory animal colonies by contaminateddrinking water. This organism may cause acute septicemia, either as anepizootic affecting mainly young guinea-pigs, or as sporadic cases in olderanimals. Death occurs rapidly, often in as little as 5 or 6 hours. At necropsy,the lymph nodes may be slightly enlarged, but few other signs are seen. P.aeruginosa infections are rare, occurring only when conditions are extremelyinsanitary.

Bostrom et al (1969) described an unusual fatal botryomycosis in an adultguinea-pig which had previously recovered from acute P. aeruginosa septicemia.The lung exudate seen at necropsy contained typical botryomycotic granules,from which P. aeruginosa was recovered in pure culture.

Streptococcus

Streptococcus zooepidemicus (Lancefield group C) is associated with severaldiseases of guinea-pigs. Subclinical infections of the upper respiratory tractare common (van der Waaij & van Bekkum, 1967), and the organism probablyenters the circulation most frequently through abrasions of the mucosa.




NATURAL INFECTlONS OF GUINEA-PIGS 127

Most commonly, S. zooepidemicus causes a chronic cervical lymphadenitis('lumps'). Fraunfelter, Schmidt, Beattie & Garner (1971) observed this con-dition over a period of 8 months in a group of 42 strain-2 guinea-pigs, where10 animals developed 'lumps'; all continued to eat well, and grew at the normalrate. These affected guinea-pigs were necropsied at regular intervals, and S.zooepidemicus isolated from the purulent material contained in the affectedlymph nodes. Fibrinopurulent pneumonia, pleuritis, pericarditis and inter-stitial nephritis were seen at necropsy in some of the animals.

Such lymph node abscesses may rupture and drain spontaneously, recurringthroughout the life of the animal (Elwood, 1971). Occasionally, there may bean associated arthritis and cellulitis, and pregnant females may abort (Cook,1969).

Bronchopneumonia due to S. zooepidemicus has been observed in guinea-pigs subjected to irradiation (van der Waaij & van Bekkum, 1967). Theorganism may also cause sporadic cases of acute, rapidly fatal pneumoniaand septicemia. Haemoglobinuria is often present, and is pathognomic ofinfection with this pathogen (Kunz & Hutton, 1971). Consolidation of thelungs, congestion of the kidneys, and myocardial necrosis are the principalfindings at necropsy. S. zooepidemicus is easily cultured from the affectedorgans, and its isolation is important in order to distinguish this infectionfrom acute salmonellosis. Control is best achieved by rapid culling of affectedanimals and their contacts, and disinfection of their quarters.

Evidence presented by Kunstyr & Matthiesen (1973) suggests that theroute of infection and the type of Streptococcus involved may differ in the twoforms of the disease. 37 of the 39 strains they isolated from sporadic casesof acute septicaemia produced p-haemolytic, M-phase colonies; they were verypathogenic for mice. On the other hand, of 8 strains from cases of cervicallymphadenitis, 5 were a- or y-hemolytic, produced S-phase colonies, and didnot kill mice. Thus, it is possible that this 'disease complex' is really 2 distinctinfections, with different inciting agents and epidemiology.

Mastitis in 2 guinea-pigs was described by Gupta, Langham & Conner(I970), who isolated an a-hemolytic Streptococcus sp. from the mammarysecretions. These workers later investigated the flora of the normal guinea-pig mammary gland (Gupta, Carter, Langham & Conner, 1972), and isolatedcr- or p-haemolytic streptococci from 22 of 298 mammary tissue samples. Alater report characterized 35 streptococcal isolates from mammary glands andmilk of normal females (Gupta & Stark, 1973). A strain each of Lancefieldgroups B, C, D, and G and 2 isolates belonging to group F were identified;29 isolates were not groupable. Their possible importance as agents of mastitisin the guinea-pig is unknown.

Even though torticollis (otitis media) is a common problem in guinea-pigs,little information on its aetiology appeared in the literature until the recent




]28 C. RIGBY

report by Kohn (1974). He examined 3] animals with torticollis, from 3different commercial breeders. S. zooepidemicus was isolated in pure culturefrom ]4, Diplococcus pneumoniae from 10, Klebsiella pneumoniae from 4, andEscherichia coli from 1. A mixed S. zooepidemicus-Proteus sp. infection wasidentified in 1 animal, and 1 yielded a mixed culture of Bordetella bronchi-septica, Streptococcus sp. (group K), and Staphylococcus aureus.

Kohn infected 6 adult guinea-pigs with S. zooepidemicus. 3 of these died(torticollis was noted in 1) and 3 were killed 20 days later. The organism wasisolated from the middle ear of all 3 that died, and from 1 of those that waskilled. This led Kohn to suggest that the streptococci may localize preferen-tially in the middle ear and, since the guinea-pig ear is anatomically similarto that of the human, and it appears that similar organisms may infect both,he also suggested that guinea-pig otitis media might be a very useful animalmodel for the study of the human infection.

Diplococcus

Diplococcus pneumoniae (especially types 3, 4, and 19) is an importantpathogen of guinea-pigs (Romer, 1962). Colonization of the upper respir-atory tract appears to be common, and when the animals are stressed byenvironmental changes or experimental manipulations, disease may result.Breeding females may be long-term carriers, since the organism tends tosequester in small abscesses in the genital tract, sometimes causing uterineinfections, stillbirths, and congenital infections of the young.

D. pneumoniae infection is probably most commonly seen as otitis media,or as the cause of sporadic cases of pneumonia and septicemia. Epizooticsalso occur, such as that reported by Keyhani & Naghshineh (1974) in a colonyof 2400 young guinea-pigs. Ventilation and sanitation had been poor in thecolony and were felt to be important predisposing factors. Clinical signs werefew; affected animals were listless and in poor condition, and died within afew days. During the first month, 450 animals were lost. At necropsy,extensive consolidation of the lungs, focal necrosis of the liver, fibrinouspleuritis, and severe congestion of all organs were observed, and D. pneumoniaetype 19 was cultured from the organs and blood. Treatment with tetracyclinecontrolled the outbreak.

D. pneumoniae grows readily on blood agar in an atmosphere of 10% carbondioxide, but we have found that some strains require incubation in an anaerobicatmosphere for primary isolation.

Because of the tendency of the organism to sequester in genital abscesses ofbreeding females, its eradication from guinea-pig colonies by the use of anti-biotics is likely to be very difficult.





StaphylococcusStaphylococcus aureus has been associated with a variety of sporadic in-

fections in guinea-pigs. Chronic staphylococcal pododermatitis in a groupof 35 adult guinea-pigs was described by Taylor, Wagner, Owens & Stuhlman(1971). The predisposing factor was thought to be the fact that the animalswere housed in cages with dirty wire flooring.

Gupta, Conner & Meyer (1972) investigated 3 cases of osteoarthritis, alsoin older animals, and isolated S. aureus from the lesions of 1.

During experiments in which foot-and-mouth disease virus was being in-jected into the footpads of guinea-pigs, Tessler (1973) noticed purulent lesionsappearing a few days after the injections. S. aureus was cultured from thepus; probably it was a skin commensal introduced into the subcutaneoustissue by the inoculation procedure.

From Germany, Weber (1973) described a sudden, severe outbreak of S.aureus infection in a commercial guinea-pig colony, which resulted in abortionsand the deaths of pregnant females. In this case, the source of infection wasthought to be the 5-year-old daughter of the owner, who was ill with staphy-lococcal pneumonia.

FungiTrichophyton CUld Microsporum

Explosive outbreaks of ringworm due to Trichophyton mentagrophytes arenot unusual in guinea-pig colonies. Microsporum canis infections are alsocommon. These dermatomycoses are extremely important because they arezoonoses. Human cases have been ascribed to contact with infected animals;in fact, according to Wood (1973), trichophytosis is the most common zoonosisof laboratory animals in the United States. Other authors, however, considerthat the strains which infect guinea-pigs are not very readily communicableto man (Clifford, 1973), and that human infection resulting from contact withinfected guinea-pigs is a rare event. In at least 1 case, however, T. menta-grophytes infection was introduced into a guinea-pig colony by an infectedtechnician (Loosli, 1967).

Infected animals suffer erythema, loss of hair, and scaling in localized patcheswhich may spread and coalesce. A Wood's lamp may be helpful in identify-ing animals infected with M. canis.

For diagnosis, affected skin and/or hairs are collected, cleared in 10%potassium hydroxide solution, and examined for the presence of fungal hyphaeand spores. A portion of the sample is also inoculated onto Sabouraud's andmycobiotic agars, and fungal growth identified by its characteristic gross andmicroscopic morphology.

Guinea-pigs seem to have a greater inherent susceptibility to ringworm in-fections than do other laboratory rodents. (Smith, Rush-Munro & McCarthy,




130 C. RIGBY

1969). In New Zealand, none of the 44 mice and 71 rats they examined wereinfected with dermatophytes; but out of 88 guinea-pigs they found 5 that wereinfected with M. canis and 65 with T. mentagrophytes. Of these, only 18 hadgrossly visible lesions, and the rest were asymptomatic carriers.

Since such asymptomatic carriers are so common, and probably are animportant source of infection, the elimination of dermatophytes from aninfected colony is very difficult (Menges, Georg & Haberman, 1957). Theadministration of griseofulvin in drinking water (Clifford, 1973), combinedwith ruthless culling of infected animals and contacts, would seem to be mosteffective.

It would be interesting to compare guinea-pig and human strains of T.mentagrophytes in order to help determine if infection with this organism istruly a zoonosis.

Absidia

Mucormycosis of guinea-pigs, caused by the 'perfect' fungi Absidia ramosaand A. corymbifera, is a benign infection which causes swelling and abscessationof the mesenteric lymph nodes. Usually no loss of condition results, and theaffected lymph nodes return to normal in 3-4 weeks. The importance of theinfection lies in the necessity of distinguishing it from the more serious lympha-denitis due to Yersinia pseudotuberculosis or Salmonella sp. This may bedone by demonstrating the fungal elements in 10% potassium hydroxidesolution mounts of pus. The condition is said to be common in some countries,presumably as a result of feeding hay contaminated with fungal spores (Neil,1972). Control, therefore, would seem to be essentially a matter of ensuringthat good food is provided.

ProtozoaEimeria

Coccidiosis of the guinea-pig, caused by Eimeria caviae, presents occasionalproblems, although the parasite is not very pathogenic (Flynn, 1973). Itsincidence in commercial colonies in North America has been estimated at6% (M. J. Walcroft, personal communication). In a severe outbreak in NewYork (Kleeberg & Steenken, 1963), the mortality was 5 % per month. Emacia-tion and enteritis were the principal signs; at necropsy the caecum was foundto be the site of infection.

Predisposing debilitating factors such as changes of environment or dietare probably required for the production of clinical disease. Since the oocystsexcreted in the faeces require about 6 days to become infective, regular clean-ing of pens every 4 or 5 days should control the infection.

Cryptosporidium

Cryptosporidium wrairii, a normal inhabitant of the guinea-pig small 1l1-





testine, may be pathogenic in some circumstances. Jervis, Merrill & Sprinz(1966) found it multiplying in the small intestine and associated it with anoutbreak of chronic enteritis. In a later report (Vetterling, Jervis, Merrill& Sprinz, 1971) these workers characterized the parasite further, and estimatedits incidence in their colony at 30-40 %. However, since reports from otherlaboratories are lacking, and since infective oocysts were not demonstrated,the importance of this parasite as a guinea-pig pathogen remains unknown.

NematodesParaspidodera

Paraspidodera uncinata is the only nematode commonly affecting guinea-pigs. This caecal worm is of low pathogenicity, and is likely to cause problemsonly in animals kept in outside pens (Haberman & Williams, 1958b). Itspresence is diagnosed by finding adult worms at necropsy, or by the detectionof ascarid-type eggs in faeces.

EctoparasitesMites

The guinea-pig mite Chirodiscoides caviae is widespread in the United States,particularly in some commercial colonies (Wagner, AI-Rabiai & Rings, 1972).The guinea-pigs in which these investigators found heavy mite infestationsshowed no signs of discomfort, but they suffered a high morbidity from D.pneumoniae infection. It was suggested that the parasitism could have beenimportant either in transmission or as a predisposing debilitating factor.

Infestation of guinea-pigs by the mange mites Mycoptes musculinis of mice,Sarcoptes scabei of rabbits and other animals, and Notoedres muris of ratshave been observed (Ronald & Wagner, ] 976). In each case the outbreakoriginated from contact with infected animals of the normal host species.While such occurrences are very rare, they serve to emphasize the need tohouse different species of animals separately.

The mite Demodex caviae has been found in the conjunctival muscle tissueof guinea-pigs suffering from a conjunctivitis (Ronald & Wagner, ]976). Noother signs of infection were observed, and the prevalence and importanceof this mite in guinea-pig colonies is unknown.

Lice

The biting lice Gyropus ovalis and Gliricola porcelli parasitize the guinea-pig,often in association with each other. Usually no discomfort is apparent inthe parasitized animal, even in heavy infestations. Trimenopon jenningsi hasbeen described from guinea-pigs, but has now become so rare that Ronald& Wagner (1976) were unable to find it in several thousand animals.




132 C. RIGBY

Control of ectoparasites is difficult in guinea-pigs. Paterson (1972) recom-mended the use of aerial insecticidal vapours, with 2-3 weeks of continuoustreatment.

VirusesLymphocytic choriomeningitis

Lymphocytic choriomeningitis (LCM) virus causes widespread subclinicalinfection in mice. The virus may cause serious disease in man, and alllaboratory animals are also susceptible. In the guinea-pig, infection may beasymptomatic, or the virus may cause a generalized pneumonia or a paralyz-ing meningoencephalitis (Obeck, 1974). Classical persistent latent LCMinfection, as it is seen in mice, is not believed to occur in guinea-pigs (Neil,1972).

LCM infection is best diagnosed by virus isolation in LCM-free animals,and by complement fixation (Blackmore, Guillon & Schwanzer, 1972).

Since mice commonly carry the virus, and ticks and mites have been shownto transmit it experimentally (Maurer, 1958), arthropod control, optimumsanitation, and the separation of mice from guinea-pigs are important incontrol. Since LCM may cause severe disease in humans, such controlmeasures are very important.

Parainfluenza I (Sendai)

Parainfluenza type I (PI-I) virus (Sendai virus) has been isolated from allof the common laboratory rodents, and is of importance because it may alsocause upper respiratory tract infections in man. In mice subclinical infectionis common and may develop into a lethal pneumonia when the animals arestressed (Blackmore et al., 1972). A similar situation is thought to exist inguinea-pigs, and outbreaks of pneumonia due to PI-I, with 100 % mortality,have been reported (Kunz & Hutton, 197]).

Diagnosis requires the isolation of the virus in embryonated eggs or culturedcells, and the demonstration of antibody by haemadsorption-inhibition(Blackmore et ai., 1972). Since infection is transmitted by the respiratoryroute, separation of mice and guinea-pigs is important in the control of thisinfection.

INAPPARENT INFECTIONS

For the purposes of this discussion, we have defined an 'inapparent infection'as a host-parasite relationship which permits the survival, growth and normalpropagation of both host and parasite. Such infections may be 'subclinical'(the parasite may be demonstrated by routine procedures) or 'latent' (the agentis not demonstrable by routine methods). This relationship may be altered





when changes in the delicate host-parasite balance either enable the host torid itself of the parasite, or permit the parasite to cause frank clinical disease.

This ill-assorted group of infections, although rarely associated with clinicaldisease, is probably far more important economically than the overt pathogens.Their unsuspected deleterious effects on experimentally-stressed animals maylead to unexplained deaths, or to misleading or erroneous results.

It is important to learn more about the incidence, pathogenesis and epi-demiology of these inapparent infections; first, in order to devise adequatecontrol methods (if such are necessary or, indeed, possible); second becauseof their possible importance as zoonoses; and, third, because in some casesat least, their similarities to known human infections may make them of valueas animal research models.

BacteriaEscherichia

Enteropathogenic Escherichia coli (predominantly serotype 0119 :B14) wasisolated from 75 % of healthy adult laboratory animals of several species bySchiff et al. (1972). These authors suggested that undiagnosed neonatal in-fections with such strains must surely be common, and could be responsiblefor many unexplained deaths in newborns. This interesting hypothesisdeserves to be investigated further, particularly since such infections couldserve as useful models for the investigation of neonatal coli bacillosis of largeanimals and humans.

ListeriaEven though human listeriosis is rather rare, its high mortality makes it an

important zoonosis. Listeria monocytogenes commonly causes inapparent in-fections in many animals, and infected animals may excrete the organism infaeces. Guinea-pigs and rabbits are, according to Wood (1973), the mostcommon hosts. Gay & Blood (1967) considered listeriosis the most seriousof all the non-primate zoonoses, precisely because of this propensity to causeinapparent infection. Opinion, however, is divided, and other workers arenot convinced that listeriosis is a zoonosis at all (Medoff, Kunz & Weinberg,1971). More research is needed into the epidemiology of this infection inguinea-pigs and other animals, and its relationship to human infection. Thenif control measures are indeed necessary, appropriate precautions can berecommended.

Leptospira

Leptospirosis is an important zoonosis, affecting domestic and wild animalsand man. Outbreaks of human leptospirosis have be'en associated with




134 C. RIGBY

mouse and rat colonies. The organism may be introduced into laboratoryanimal colonies by infected wild rodents which excrete the organism in urine.Once established the infection is difficult to eradicate, since recovered animalsmay remain carriers indefinitely (Wood, 1973).

Leptospirosis is diagnosed in the laboratory partly by the inoculation ofguinea-pigs. This method, of course, presupposes the absence of spontaneousinfection in these animals. There is, however, a report (Mason, 1937) of aguinea-pig colony becoming infected by wild rats. Only 1 animal had clinicaljaundice: it died, and Leptospira icterohaemorrhagica was isolated from theliver and lungs. Other apparently healthy adults of the colony were sub-sequently found to be refractory to experimental infection, and some of thesehad agglutination titres as high as 1 :300 to L. icterohaemorrhagica. In viewof this report, if there is any history of a colony having been exposed to wildrodents, it should be established serologically that the animals are indeed freeof leptospiral infection before they are used for research or diagnosis.

ProtozoaKlossiella

The renal coccidian Klossiella cobayae is common in guinea-pigs and gener-ally considered to be nonpathogenic. Of 108 guinea-pigs examined by Hof-mann & Hanichen (1970) in Germany, 30 % were found to be infected. Theseauthors, however, observed a chronic nephritis and described degenerativelesions seen on histopathology. They considered that K. cobayae was respon-sible for these lesions, and suggested that disease due to this coccidian maybe more common than is generally supposed.

Pneumocystis

Pneumocystis carinii is an important cause of interstitial pneumonia in humaninfants and debilitated adults (Woodruff, 1971). The protozoon was firstdescribed in microscopic sections of the lungs of normal guinea-pigs, and is acommon commensal of rodents and other animals (Faust & Russell, 1964).The mode of infection of humans is unknown, but presumably sporozoitesderived from carrier animals are inhaled (Audy & Dunn, 1972). Obviouslythere is a great need to clarify the epidemiology of this parasite.

Toxoplasma

Spontaneous Toxoplasma gondii infection of guinea-pigs, with infection ratesas high as 33 % (as detected by the dye test) has been reported from the UnitedStates and Europe (Neil, 1972). Inapparent infections are most common;with stress of some kind, a chronic wasting may be evident, and the affectedanimals very gradually become extremely lethargic and die. Prolonged,





asymptomatic parasitaemia has been observed in experimentally infectedguinea-pigs (Frenkel, 1973). Diagnosis depends on the dye test or immuno-fluorescence, or on histological demonstration of encysted parasites in thetissues.

The effect of T. gondii infection upon the response of guinea-pigs to experi-mental procedures is, according to Shadduck & Pakes (1971), likely to be con-siderable.

Since cats are the only animals which have so far been shown to excreteinfective oocysts, guinea-pig toxoplasmosis is not likely to present a threat tohuman health.

Intrauterine transmission of T. gondii in experimentally-infected guinea-pigshas been demonstrated (Wright, ] 972). Because the mode of transmissionof the natural infection is still unknown, specific preventive measures have notyet been formulated.

Encephalitozoon

Encephalitozoon (Nosema) infection may be difficult to differentiate fromtoxoplasmosis. No clinical signs are evident, the organism producing amildly contagious, chronic infection (Yost, 1958). The mode of transmissionis unknown. Little is known about the incidence or effects of Encephalitozooninfection in guinea-pigs (Griffiths, 1971), but some colonies of mice and ratshave infection rates of 20-50% (Shadduck & Pakes, 1971). Sporadic caseshave been described in guinea-pigs, the typical lesions in kidney and brainbeing detected as incidental findings by histological examination (Moffatt &Scheifer, 1973). Their importance lies chiefly in the difficulty of interpretinghistological findings when infected animals are used for experimental purposes.

In rabbits, latent infection with E. cuniculi changes the course of someexperimental infections and transplantable tumours (Shadduck & Pakes, 1971).These authors (Pakes, Shadduck & Olsen, 1972) have developed a diagnosticskin test for encephalitozoonosis in rabbits, which they claim is sensitive andspecific, and can be used to select un infected rabbits for breeding stock.Application of this test to guinea-pigs could yield valuable information on theincidence of this microsporidianin guinea-pig colonies, and afford a meansof obtaining Encephalitozoon-free stock.

VirusesCytomegalovirus

Guinea-pig cytomegalovirus (CMV) was first described almost 50 years agoby Cole & Kuttner (1926) who found typical CMV-type inclusion bodies inthe salivary gland ductal epithelium of 84 % of normal adult guinea-pigs.Guinea-pigs less than a month old were free of infection.

CMV infection of guinea-pigs is usually inapparent, but severe generalized




136 C. RIGBY

disease may occur in association with some stress factor such as a concurrentrespiratory infection (Blackmore et aI, 1972). Diagnosis is made by virusisolation in cultured cells, or by the demonstration of typical CMV inclusionbodies in the epithelial cells of the kidney, liver and bronchi. Transmissionis probably by direct contact, since CMV is excreted in the urine and saliva.

Guinea-pig CMV is similar to other cytomegaloviruses in its replicationcycle in infected cells (Hartley, Rowe & Huebner, 1957) and as seen by electronmicroscopy (Middelkamp, Patrizi & Reed, 1967). The disease is importantin the animal colony principally as it may affect the responses of animalsinoculated experimentally with other agents (Cook, 1969). Guinea-pig CMVinfection may serve as a useful model for the study of human CMV infection(Ditchfield, 1968).

Oncornavirus

The induction of an oncornavirus by 5-bromodeoxyuridine treatment ofcultured guinea-pig fibroblasts and tumour cells was first reported by Opler(1967). It has since been studied rather intensively by several workers, andthere is an ongoing controversy about its identity as a type B or type C oncoma-virus (Dahlberg, Perk & Dalton, 1974). It is similar morphologically andbiochemically to the Gross murine leukaemia virus (Type C), but is serologicallydistinct (Murray & Nayak, 1974). Hsiung & Fong 1974) isolated a C-typevirus from all guinea-pigs they tested, both normal and leukaemic. Thepossible association of this oncornavirus with leukaemia in the guinea-pig,and its relationship to other human and animal tumour viruses, remain to beclarified.

Parvovirus

Green (1974) isolated a parvo-like virus from the tissues of guinea-pigswhich had been treated with penicillin. This antibiotic has long been knownto be lethal to guinea-pigs, and Green has put forth the interesting theory thatthis effect may be associated with the activation of a latent parvovirus.

Herpes-like virus

Guinea-pig herpes-like virus (HLV) has been studied rather intensively sinceits first isolation from guinea-pig kidney cell cultures (Hsiung & Kaplow,1969). HLV infection in guinea-pigs is inapparent, and the virus seems tobe truly latent, since its isolation required organ culture or co-cultivationmethods (Bhatt, 1971; Lam & Hsiung, 1973). Its incidence varied in differentstrains of animals: 90% of 40 strain-2 (leukaemia-susceptible) but none of 40Hartley strain (leukaemia-resistant) guinea-pigs carried the virus (Hsiung,Kaplow & Booss, 1971). Experimentally, HLV could be transmitted trans-





placentally (Lam & Hsiung, 1971a) as well as orally and intranasally (Lam &Hsiung,1971b).

The similarities of HLV to human herpesviruses led Booss & Hsiung (1971)to suggest that it may make a valuable animal model for the study of per-sistent herpesvirus infections in humans.

Other agentsChlamydia

A guinea-pig inclusion-body conjunctIvItIs agent was detected by Murray(1964) in conjunctival scrapings from 32 of 144 guinea-pigs tested. Evidenceof infection was very slight, and disappeared spontaneously in about 3 weeks.The agent grew in embryonated eggs, and was identified as a member of theChlamydiae by the presence of the common group antigen. Watson, Mull,MacDonald, Thompson & Bear (1973) have taken advantage of its similarityto human trachoma, and used it in their studies on this infection.

Robinson (1969) isolated a chlamydial agent from 4 of 15 normal adultguinea-pigs. The organism was identified as the ovine enzootic abortionagent by complement fixation. 15 years previously, guinea-pigs from thecolony had had access to grass paddocks grazed by sheep experimentally in-fected with this agent, and this was thought to be the original source of theinfection. If so, the inapparent infection had presumably been maintainedin the guinea-pig colony by mother-offspring transmission for 15 years.

Mycoplasma

Mycoplasma of guinea-pigs were first reported by Hill, Blackmore & Francis(1969), who isolated a new species, later identified as Mycoplasma caviae(Hill, ]97]0) from 10 of 232 guinea-pigs examined. The isolates, mostlyfrom the genital tract, were not associated with disease, except possibly witha metritis in 1 animal. This association suggested a possible relationship toabortions and other reproductive problems, as have been postulated for myco-plasmas in other animals (Razin, 1973).

Since then, several other guinea-pig mycoplasmas have been described. InGermany, M. pulmonis, a pathogen of the uterus of mice and rats (Casillo &Blackmore, 1972), was isolated from the uterus of all of 80 pregnant and non-pregnant females (J uhr and Obi, 1970): the significance of this finding is difficultto assess (Hill, 197Ib). 2 other un-named species were later isolated from thevaginas of healthy females (Hill, 1971c) and, more recently, Acholeplasmalaidlawii was isolated from the nasopharynx and vagina of guinea-pigs originat-ing from 4 different colonies (Hill, 1974). Stalheim & Matthews (1975) con-firmed Hill's observations, and isolated 3 unidentified species of Mycoplasmafrom guinea-pigs in the United States. Thus it appears that the guinea-pig,




138 C. RIGBY

like every other animal so far investigated, is host to a variety of species ofMycoplasma whose pathogenic potential is still largely unknown.

HaemobartonellaThe genus Haemobartonella (formerly thought to be a protozoon) is now

included in the order Rickettsiales. Members of this genus infect many.laboratory and domestic animals. Haemobartonella tyzzeri (caviae) of guinea-pigs produces an inapparent infection which becomes evident as an acutehaemolytic anaemia after experimental stress such as splenectomy (Griesemer,1958). The small beaded bacillus-like organisms are found attached to theplasmalemma of erythrocytes of infected guinea-pigs, but because overt in-fections are transient and Haemobartonella may be confused with erythrocyticinclusions, diagnosis by the examination of blood smears may be unreliable. Theinfection is best diagnosed by inoculation of known uninfected splenectomizedguinea-pigs. Haemobartonella infection is transmitted by lice and may occur inutero; Baker et al. (1971) review research implications due to this type of infectionin rats and mice, and it is possible that similar situations exist in guinea-pigs.If so, then it is clearly important to define the problem and devise adequatemeasures to ensure that biomedical research in these animals is not needlesslycomplicated by the unsuspected presence of Haemobartonella.

COMMENTS

Good management is crucial in the prevention and control of infectiousdisease in the guinea-pig, as in all laboratory animals. Proper housing,adequate ventilation, sanitation, and temperature and humidity control areall-important, as is the provision of well-balanced diets.

There is still, however, a need for improved record-keeping, diagnosticmethods, and a better understanding of the epidemiology and pathogenesisof agents such as Streptococcus zooepidemicus, Diplococcus pneumoniae andothers. The appropriate knowledge, combined with frequent surveillance, willpermit early detection and diagnosis of infection. Then specific measurescan immediately be taken to ensure that animal losses due to infectious diseaseare minimal.

Inapparent infections pose a different type of problem, more difficult toresolve because more difficult to detect. Such infections are likely to becomemore important because of their deleterious effects on experimental animals,similarities to problems in human medicine, and possible zoonotic significance.Procedures for the establishment of 'germ-free' or 'S.P.F.' animals may notensure their freedom from potential pathogens such as Toxoplasma gondii,Listeria monocytogenes, and herpesviruses, which may be transmitted trans-placentally. Clearly, more work is needed to improve our understanding ofthese infections and their effects on experimental animals.




NATURAL INFECTIONS OF GUINEA-PIGS

ACKNOWLEDGEMENTS

139

The author gratefully acknowledges the helpful CrItIcIsm received from DrC. H. Bigland, Dr F. M. Loew, and Dr E. D. Olfert during the preparation ofthis manuscript.

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Natural infections of guinea-pigs