Diseases of Guinea Pigs PAT 707, Diseases of Laboratory Animals II Prepared by Trenton R. Schoeb Department of Comparative Medicine University of Alabama at Birmingham Winter Quarter 1989-90 Guinea Pig Cytomegalovirus 1. Agent: A herpesvirus of the subfamily Betaherpesvirinae; syn. caviid herpesvirus type 1. 2. Epizootiology: Thought to be common if not ubiquitous in conventional colonies, but good data are lacking. Transmitted via saliva, conjunctiva, urine, and placenta. 3. Signs & lesions: Disease is rare. In ordinary infections, inclusions may be present in salivary glands, cervical lymph nodes, and kidney (nuclear inclusions with cytomegaly in salivary glands, nuclear inclusions without cytomegaly in kidney). There may be peripheral mononucleosis. Disseminated disease occurs rarely, and does not feature specific signs. In some of the few cases reported, and it was not establishedwhether or not the affected animals were immunosuppressed. Neonates and pregnant sows seem to be more susceptible, however; fatal generalized disease, stillbirths, and abortions have been reported. 4. References: Bia FJ et al. 1979. Cytomegaloviral infection in guinea pigs. III. Persistent viruria, blood transmission, and viral interference. J Infect Dis 140:914-920. Bia FJ et al. 1980. Vaccination for the prevention of mate biomedical research. Microbiol Rev 4:468-490. Griffith BP et al. 1981. Cytomegalovirus-induced mononucleosis in guinea pigs. Infect Immun 32:857-863. Griffith BP et al. 1983. Enhancement of cytomegalovirus infection during pregnancy in guinea pigs. J Infect Dis 147:990-998. Griffith BP, Hsiung GD. 1980. Cytomegalovirus infection in guinea pigs. IV. Maternal infection at different stages of gestation. J Infect Dis 141:787-793. Griffith BP, Lucia HL, Hsiung GD. 1982. Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs. Pediatr Res 16:455-459. Johnson KP, Connor WS. 1979. Guinea pig cytomegalovirus: transplacental transmission. Arch Virol 59:263-267. Kumar ML, Nankervis GA. 1978. Experimental congenital infection with cytomegalovirus: a guinea pig model. J Infect Dis 138:650-654. Motzel SL, Wagner JE. 1989. Diagnostic exercise: fetal death in guinea pigs. Lab Anim Sci 39:342-344. Pappenheimer AM, Slanetz CA. 1942. A generalized visceral disease of guinea pigs associated with intranuclear inclusions. J Exp Med 76:299-306. Van Hoosier GL Jr et al. 1985. Disseminated cytomegaloviral disease in the guinea pig. Lab Anim Sci 35:81-84. Van Hoosier GL Jr, Robinette LR. 1976. Viral and chlamydial diseases. In The Biology of the Guinea Pig; Wagner JF, Manning PJ (eds.), Academic Press, New York, 1976, pp. 137-152. Adenovirus Reported from West Germany and US; prevalence unknown. Morbidity and mortality in reported cases was low, and transmissibility also appeared low. Disease as expected, with dyspnea clinically; patchy gross pneumonia; necrotizing bronchiolitis with interstitial pneumonia and with typical nuclear inclusions. The diagnosis in both cases was based on EM findings. The virus has not been isolated. Brennecke LH et al. 1983. Naturally occurring virus associated respiratory disease in two guinea pigs. Vet Pathol 20:488-491. Feldman SH, Richardson JA, Clubb FJ Jr. 1990. Necrotizing viral bronchopneumonia in guinea pigs. Lab Anim Sci 40:82-83. Kaup FJ et al. 1984. Experimental viral pneumonia in guinea pigs: an ultrastructural study. Vet Pathol 21:521-527. Kunstyr I et al. 1984. Adenovirus pneumonia in guinea pigs: an experimental reproduction of the disease. Lab Anim 18:55-60. Naumann S et al. 1981. Lethal pneumonia in guinea pigs associated with a virus. Lab Anim 15:235-242. Retrovirus Guinea pigs have an endogenous type C retrovirus, but its significance has not been ascertained. L2C "leukemia," discovered in strain 2 guinea pigs in the early 1940s and maintained since by serial cell passage, may be caused by this virus. (Inoculation of cell-free material does not cause the disease.) Affected animals have lymphadenopathy, splenomegaly, and hepatomegaly. Peyer's patches and bone marrow also are affected, and there is lymphocytosis of up to 250,000/mm3 with circulating lymphoblasts. Kaplow LS, Nadel E. 1979. Animal model. Acute lymphoblastic leukemia: transplantable guinea pig L2C leukemia. Am J Pathol 95:273-276. Rhim JS, Green I. 1977. Guinea pig L2C leukemia: immunological, virological, and clinical aspects. Fed Proc 36:2247-2332. Other Viruses 1. Guinea Pig "Herpes-like" Virus A true herpesvirus, syn. caviid herpesvirus type 2. Persistent infection without inclusions or cytomegaly. Virus recoverable from many tissues and from leukocytes. Significance unknown. May cause stillbirths and reduced birth weights. Isolation and identification of virus is best method of diagnosis, inasmuch as there is poor correlation of serologic response with infection. Connelly BL, Keller GL, Myers MG. 1987. Epizootic guinea-pig herpes-like virus infection in a breeding colony. Intervirology 28:8-13. Dowler KW et al. 1984. Lymphoproliferative changes induced by infection with a lymphotropic herpesvirus of guinea pigs. J Infect Dis 150:105-111. 2. Guinea Pig "X" Virus Syn. caviid herpesvirus type 3. Distinct from the other two herpesviruses of guinea pigs by serology and DNA hybridization. No known natural disease, but experimental inoculation caused focally necrotizing hepatitis with up to 50% mortality within 11 weeks. Bia FJ et al. 1980. New endogenous herpesvirus of guinea pigs: biological and molecular characterization. J Virol 36:245-253. 3. Miscellaneous viruses Serologic evidence for other viral infections has been found, but no disease is known. These viruses include parainfluenza types 1 (Sendai), 2, 3, and 5; pneumonia virus of mice; reovirus type 3; lymphocytic choriomeningitis virus; and Theiler's virus. Sendai and SV-5 viruses have been isolated from guinea pigs. Streptococcal Lymphadenitis 1. Agent: Streptococcus zooepidemicus, a á-hemolytic Streptococcus of Lancefield Group C. 2. Epizootiology: Common infection. Strain 2 animals are said to be more susceptible than strain 13, but this has not been proven experimentally. Transmission probably by oral and conjunctival routes via aerosols and fomites. Acute epizootics are more likely to occur in weanling animals. Morbidity and mortality may be high. 3. Clinical: Adults usually have chronic infection characterized by cervical lymphadenitis. Nodes may be enlarged to 2 cm diameter or greater, may rupture and drain to skin surface followed by healing and fibrosis. Young animals tend to have septicemic spread of infection to many organs. 4. Pathology: Organism reaches cervical nodes from nasopharynx or conjunctiva by lymphatics. Basic lesion is suppurative lymphadenitis. In animals with disseminated infection, suppurative inflammation may occur in virtually any organ or tissue; common lesions include pneumonia, pericarditis, myocarditis, pleuritis, peritonitis, meningitis, and otitis media. 5. Diagnosis: Characteristic lesions and isolation of organism. Myriads of gram-positive cocci are seen in gram-stained sections of lesions. 6. Control: Eliminate stock and replace with disease free animals. Culling and treatment with antibiotics are generally useless. Streptococcal Pneumonia 1. Agent: Streptococcus pneumoniae, an à-hemolytic Streptococcus. Lancet-shaped, gram- positive cocci arranged in pairs or short chains. Types 4 and 19 are most common in guinea pigs. 2. Epizootiology: Carrier state in infected colonies may be high (e.g., 55%). Outbreaks tend to be associated with stressful factors such as temperature changes, shipment, experimental manipulations, etc. 3. Clinical: Anorexia, ruffled fur, wet nose and dyspnea; abortion; or deaths without signs. 4. Pathology: Basic lesion is suppurative bronchopneumonia; however, a variety of other lesions also have been reported. These include fibrinopurulent pleuritis, pericarditis, peritonitis, otitis media, endometritis, meningitis, arthrititis, and osteomyelitis. Such lesions indicate that bacteremia or septicemia is common. 5. Diagnosis: Characteristic lesions, isolation of organism. 6. Control: Sulfadiazine or tetracycline treatment may help control epizootics but do not eliminate organism. Best to eliminate infected stocks and repopulate. 7. References: Matsubara J et al. 1988. Serodiagnosis of Streptococcus pneumoniae infection in guinea pigs by an enzyme-linked immunosorbent assay. Lab Anim 22:304-308. Parker GA et al. 1977. Extrapulmonary lesions of Streptococcus pneumoniae infection in guinea pigs. Vet Pathol 14:332-335. Thore M et al. 1982. Streptococcus pneumoniae and three species of anaerobic bacteria in experimental otitis media in guinea pigs. J Infect Dis 145:822-828. Witt WM, Hubbard GB, Fanton JW. 1988. Streptococcus pneumoniae arthritis and osteomyelitis with vitamin C deficiency in guinea pigs. Lab Anim Sci 38:192-194. Bordetellosis 1. Agent: Bordetella bronchiseptica, a short gram-negative rod or coccobacillus. 2. Epizootiology: Colony infection is maintained by carriers which may exceed 20% of the animals in a colony. Carriers harbor organism in upper respiratory tract. Close contact thought to be essential for transmission. 3. Clinical: Signs are nonspecific; dyspnea common. 4. Pathology: Blood-tinged exudate around external nares, frothy blood-tinged exudate in trachea, serous fluid in pleural cavity, patchy consolidation of lungs. Microscopically, purulent tracheitis and bronchitis, fibrinous bronchopneumonia. Uterine infection may cause stillbirths, abortions, infertility, salpingitis. 5. Diagnosis: Lesions, tissue gram stain, culture. 6. Control: Reported that formalin- or merthiolate-killed bacterins may be used to eradicate colony infection. 7. References: Baskerville M et al. 1982. A study of chronic pneumonia in a guinea pig colony with enzootic Bordetella bronchiseptica infection. Lab Anim 16:290-296. Endoh M et al. 1986. Purification and characterization of heat-labile toxin from Bordetella bronchiseptica. Microbiol Immunol 30:659-673. Matherne CM et al. 1987. Efficacy of commercial vaccines for protecting guinea pigs against Bordetella bronchiseptica pneumonia. Lab Anim Sci 37:191-194. Trahan CJ et al. 1987. Airborne-induced experimental Bordetella bronchiseptica pneumonia in strain 13 guinea pigs. Lab Anim 21:226-232. Salmonellosis 1. Agent: Salmonella enteritidis, serotypes enteritidis and typhimurium are most common. 2. Epizootiology: Major sources of infection are contaminated food. Animals which recover from acute infection become carriers, shed organism in feces intermittently. Mortality can approach 100%. 3. Clinical: Unexpected deaths, anorexia, conjunctivitis. Diarrhea rarely seen. Mortality greatest in young and in dams at parturition. 4. Pathology: Focal necrosis in liver, spleen and mesenteric nodes; splenomegaly. Microscopically, pyogranulomatous foci in many organs, particularly liver, spleen and lymphoid organs. These foci may by grossly visible. In some cases, purulent peritonitis, pleuritis and pericarditis. 5. Diagnosis: Characteristic lesions, isolation of organism. 6. Control: Depopulate, sanitize premises and repopulate with Salmonella-free stock. 7. References: Okewole PA et al. 1989. Uterine involvement in guinea pig salmonellosis. Lab Anim 23:275-277. Onyekaba CO. 1983. Clinical salmonellosis in a guinea pig colony caused by a new Salmonella serotype, Salmonella ochiogu. Lab Anim 17:213-216. Staphylococcosis 1. Agent: Staphylococcus aureus. 2. Pathology: Most common is chronic pododermatitis resulting from infection following trauma (such as housing on rusty wire floors); also possibly pneumonia, mastitis and conjunctivitis. Recently, an exfoliative skin disease due to staphylococcal infection in strain 13 guinea pigs was reported from Japan. The disease was most common in pregnant females. It was characterized by 1-2 days of erythema of skin on the ventral abdomen and thorax, 4 to 7 days of desquamation, healing of skin after another week, and regrowth of hair by 2 months after onset. No adults died. Mortality among neonates and suckling young of affected dams was 88% compared to 47% of young born to normal dams. Microscopically, there was cleavage of epithelium through the stratum granulosum with minimal or no inflammation in the underlying epidermis. The disease was reproduced experimentally by injecting disease free guinea pigs subcutaneously with the isolated S. aureus. The disease was compared to the "scalded skin syndrome" of children. 3. Reference: Ishihara C. 1980. An exfoliative skin disease in guinea pigs due to Staphylococcus aureus. Lab Anim Sci 30:552-557. Clostridial Enterotoxemia Similar to the disease in rabbits and other species. Administration of antibiotics alters cecal flora, allowing clostridia to proliferate and elaborate toxin. The condition has followed administration of penicillin, erythromycin, chlortetracycline, oxytetracycline, streptomycin, and bacitracin. It was once thought that antibiotics caused a shift in intestinal flora from predominantly gram positive organisms to gram negative ones, leading to enterocolitis and gram negative septicemia. Recent evidence, however, indicates that bacterial septicemia is a terminal event and that clostridial toxins, particularly those of Clostridium difficile, are primarily responsible. Boot R, Angulo AF, Walvoort HC. 1989. Clostridium difficile-associated typhlitis in specific pathogen free guinea pigs in the absence of antimicrobial treatment. Lab Anim 23:203-207. Lowe BR et al. 1980. Clostridium difficile-associated cecitis in guinea pigs exposed to penicillin. Am J Vet Res 41:1277-1279. Rehg JE et al. 1980. Toxicity of cecal filtrates from guinea pigs with penicillin- associated colitis. Lab Anim Sci 30:524-531. Rothman SW. 1981. Presence of Clostridium difficile toxin in guinea pigs with penicillin-associated colitis. Med Microbiol Immunol 169:187-196. Chlamydiosis ("Inclusion Conjunctivitis") 1. Agent: Chlamydia psittaci. 2. Clinical: Apparently a rare cause of spontaneous conjunctivitis. May be subclinical. 3. Pathology: Mild purulent conjunctivitis. Initial and elementary bodies may be demonstrated in Giemsa-stained conjunctival epithelial cells. 4. Control: Uncertain. Probably a self-limiting infection. 5. Reference: Barron AL et al. 1979. Target tissues associated with genital infection of female guinea pigs by the chlamydial agent of guinea pig inclusions conjunctivitis. J Infect Dis 139:60-68. Deeb BJ, DiGiacomo RF, Wang SP. 1989. Guinea pig inclusion conjunctivitis (GPIC) in a commercial colony. Lab Anim 23:103-106. Tyzzer's Disease Clinically, diarrhea and death. Lesions are multifocal necrotizing ileitis, cecitis, and colitis. Hepatitis appears to be less common than in other species. Boot R, Walvoort HC. 1984. Vertical transmission of Bacillus piliformis infection (Tyzzer's disease) in a guinea pig: case report. Lab Anim 18:195-199. Dillehay DL, Lindsey JR. 1988. Diagnostic exercise: diarrhea in guinea pigs. Lab Anim Sci 38:472-473. McLeod CG et al. 1977. Intestinal Tyzzer's disease and spirochetosis in a guinea pig. Vet Pathol 14:229-235. Sparrow S, Naylor P. 1978. Naturally occurring Tyzzer's disease in guinea pigs. Vet Rec 103:288. Waggie KS et al. 1986. Naturally occurring Bacillus piliformis infection (Tyzzer's disease) in guinea pigs. Lab Anim Sci 36:504-506. Zwicker GM et al. 1978. Naturally occurring Tyzzer's disease and intestinal spirochetosis in guinea pigs. Lab Anim Sci 28:193-198. Yersiniosis Uncommon or rare in US. Multifocal necropurulent enteritis, mesenteric lymphadenitis, hepatitis, splenitis, nephritis, pneumonia. Miscellaneous Bacterial Infections 1. Proliferative enteritis A single case of duodenal hyperplasia was reported in a 3-1/2 month old female. There was mucosal hyperplasia of the proximal duodenum. The apical cytoplasm of the affected epithelium contained bacilli similar to the Campylobacter-like organisms in proliferative ileitis of hamsters and proliferative colitis in ferrets. A similar condition has been reported from Japan. Elwell MR et al. 1981. Duodenal hyperplasia in a guinea pig. Vet Pathol 18:136-139. Muto T et al. 1983. Adenomatous intestinal hyperplasia in guinea pigs associated with Campylobacter-like bacteria. Jpn J Med Sci Biol 36:337-342. 2. Citrobacter freundii septicemia and pneumonia C. freundii was the apparent cause of septicemia with fibrinopurulent pleropneumonia and septic thrombi in the lung, liver, and spleen in a colony of guinea pigs in Nigeria. One hundred fifteen of 1300 animals died, and weanlings appeared to be more susceptible than older guinea pigs. It is likely that unidentified predisposing factors were present, but none was identified. We have seen similar disease in a few guinea pigs. We isolated various coliforms, not including C. freundii, from the lungs. Ocholi RA et al. 1988. An epizootic infection of Citrobacter freundii in a guinea pig colony: short communication. Lab Anim 22:335-336. 3. Mycoplasmal infections Mycoplasma caviae is a nonpathogenic species which has been isolated from nasopharynx and vagina. Mycoplasma pulmonis has been isolated from the vagina, but is not known to cause disease in guinea pigs. 4. Cilia-associated respiratory (CAR) bacillus Guinea pigs inoculated with CAR bacillus in the form of infected rat lung homogenate seroconverted but did not develop any disease, and no bacilli were identified in their tissues. Matsushita S et al. 1989. Transmission experiments of cilia-associated respiratory bacillus in mice, rabbits and guinea pigs. Lab Anim 23:96-102. Dermatophytosis Considered one of the more common skin diseases of guinea pigs. Primarily due to Microsporum spp. and Trichophyton spp. (T. mentagrophytes is most common.) Clinical signs, diagnosis, pathology and control are the same as in other species. Aho R. 1980. Studies on fungal flora in hair from domestic and laboratory animals suspected of dermatophytosis. Acta Pathol Microbiol Scand 88:79-83. Hironaga M et al. 1981. Trichophyton mentagrophytes skin infections in laboratory animals as a cause of zoonosis. Mycopathol 73:101-104. Protozoa 1. Eimeria caviae Cecum & colon; colitis; blood-flecked watery diarrhea Hankinson GJ et al. 1982. Diagnostic exercise. Eimeria caviae infection. Lab Anim Sci 32:35-36. Kunstyr I, Naumann S. 1981. Coccidiosis in guinea pigs; with emphasis in diagnosis. Z Versuchstierkd 23:255-257. 2. Cryptosporidium wrairi Ileum; chronic enteritis, weight loss Gibson SV, Wagner JE. 1986. Cryptosporidiosis in guinea pigs: a retrospective study. J Am Vet Med Assoc 189:1033-1034. 3. Encephalitozoon cuniculi Kidney, brain; chronic tubulointerstitial nephritis, multifocal granulomatous encephalitis Boot R et al. 1988. Serological evidence for Encephalitozoon cuniculi infection (nosemiasis) in gnotobiotic guineapigs. Lab Anim 22:337-342. Gannon J. 1980. A survey of Encephalitozoon cuniculi in laboratory animal colonies in the United Kingdom. Lab Anim 14:91-94. Moffat RE, Schiefer B. 1973. Microsporidiosis (encephalitozoonosis) in the guinea pig. Lab Anim Sci 23:282-284. 4. Others, no disease reported. Giardia caviae (small intestine, esp. duodenum); Entamoeba caviae (colon); Tritrichomonas caviae (colon); Balantidium caviae (colon); Klossiella cobayae (kidney) 5. Toxoplasma gondii Henry L, Beverly JKA. 1976. Toxoplasmosis in rats and guinea pigs. J Comp Pathol 87:97-102. Helminth 1. Paraspidodera uncinata A heterakid; cecum and colon; nonpathogenic. Ectoparasites 1. Trixacarus caviae A sarcoptid mite smaller than Sarcoptes scabiei. T. caviae causes mange which can be severe enough to be fatal if untreated. Clinically, there is intense pruritus, self-trauma, furious running about the cage and blindly running into objects. Lesions affect mainly the head, neck, shoulders, back, and sides. Sarcoptes scabiei and Notoedres muris also cause sarcoptic mange in guinea pigs. Dorrestein GM, Van Bronswijk JEMH. 1978. Trixacarus caviae (Sarcoptidae) infection in guinea pigs. Vet Pathol 15:576. Kummel BA et al. 1980. Trixacarus caviae infestation of guinea pigs. J Am Vet Med Assoc 177:903-908. McDonald SE, Lavoipierre MMJ. 1980. Trixacarus caviae infestation in two guinea pigs. Lab Anim Sci 30:67-70. Rothwell TL, Pope SE, Collins GH. 1989. Trixacarus caviae infection of guinea pigs with genetically determined differences in susceptibility to Trichostrongylus colubriformis infection. Int J Parasitol 19:347-348. Zajac A et al. 1980. Mange caused by Trixacarus caviae in guinea pigs. J Am Vet Med Assoc 177:900-903. Zenoble RD, Greve JH. 1980. Sarcoptid mite infestation in a colony of guinea pigs. J Am Vet Med Assoc 117:898-900. 2. Chirodiscoides caviae (Listrophoridae) Fur mite. Infestation usually asymptomatic; if heavy, may cause pruritus, alopecia. Lemeij JT, Cremers HJ. 1986. Anorexia and Chirodiscoides caviae infection in a guinea pig (Cavia porcellus). Vet Rec. 119:432. Wagner JE et al. 1972. Chirodiscoides caviae infestation in guinea pigs. Lab Anim Sci 22:750-752. 3. Gyropus ovalis, Gliricola porcelli (Gyropidae, chewing lice). Usually asymptomatic; if heavy infestation, may cause alopecia, rough coat. 4. Demodex caviae (Demodicidae) Incidence and significance not known. 5. Myocoptes musculinis (Myocoptidae) Reported once. Diabetes Mellitus Spontaneous diabetes mellitus was first reported in Abyssinian guinea pigs in 1973. The disease purportedly resembles juvenile diabetes in man. Epizootiologic evidence favors an infectious cause: About half of a group of females introduced into the colony as breeders developed the disease in 6 weeks to 3 months. Plaques in embryonated eggs inoculated with urine of affected guinea pigs contained viral particles resembling type C retrovirus. Onset is usually by 6 months; about 50% of animals in a colony develop the disease based on abnormal glucose tolerance tests and glucosuria. (Glucose in urine exceeding 100 mg/100 ml is considered glucosuria in guinea pigs.) Affected guinea pigs commonly have up to 250 mg/ml glucose in the urine, and some have more. Some guinea pigs may have remissions associated with regeneration of beta cells. Unlike affected humans, diabetic guinea pigs do not develop ketoacidosis. Characteristic islet lesions include degranulation of beta cells; increase in granular ER in beta cells, which appears as "basophilic bodies" by light microscopy; cytoplasmic "inclusions," which resemble glycogen mixed with beta-granule cores, in beta cells; fibrosis and scarring of islets; and fibroblasts in islets. Pancreatic acini can undergo fatty degeneration. Renal lesions can occur in cases of more than 6 months duration, and include diffuse thickening of glomerular basal lamina and expansion of the mesangial core. Microangiopathy also is reported, and bilateral cataracts have been observed. Lang CM et al. 1977. The guinea pig as an animal model of diabetes mellitus. Lab Anim Sci 27:789-805. Lang CM, Munger BL. 1976. Diabetes mellitus in the guinea pig. Diabetes 25:434-443. Lee KJ et al. 1978. Isolation of virus-like particles from the urine of guinea pigs with spontaneous diabetes mellitus. Vet Pathol 15:663-666. Scurvy Like primates and certain other animals, guinea pigs lack l-gluconolactone oxidase, an enzyme needed to synthesize ascorbic acid from glucose. Guinea pigs require at least 5 mg ascorbic acid per day for normal growth and reproduction. Clinical signs of deficiency are vague, and include weakness, anorexia, lassitude, weight loss, and anemia. Affected animals may appear to be ataxic or to have posterior paresis. There may be swelling of the stifle joints and hind feet. Even before clinical manifestations appear, changes are said to be present in odontoblasts and epiphyses. There is lack of normal osteoid formation, dense mineralization of spicules present, and widening of costochondral joints. Hemorrhages may occur anywhere: subcutis, joints, muscle, intestine. There may be spontaneous fractures (mainly at proximal end of tibia in our experience). Cases have been described in which classic signs were not present. Affected guinea pigs had diarrhea, weight loss, and dehydration. The jejunum, cecum, and colon were atonic and hyperemic. Histologically, there was edema and hyperemia of the lamina propria of the intestine with a mononuclear infiltrate of the lamina propria and submucosa, and there was free blood, neutrophils, or both in the lumen. Bone lesions were characteristic of the disease in the early stages, and included reduced osteoid formation, reduction in bony trabeculae, thin epiphyses with fewer than normal chondrocytes that formed irregular columns, maturation sequences that varied from little maturation to normal, little osteoblastic activity, and increased osteoclastic activity in regions of calcified cartilage. Deficiency results from inadequate diet or mishandling of feed. Vitamin C is labile to heat and light, and even well-stored feed eventually loses activity; therefore, after 90 days after the date of manufacture, feed may not contain enough vitamin C. Best to supplement ascorbic acid in water; mix it fresh at least every other day and provide 5-10 mg per adult guinea pig per day. Clarke GL et al. 1980. Subclinical scurvy in the guinea pig. Vet Pathol 17:40-44. Witt WM, Hubbard GB, Fanton JW. 1988. Streptococcus pneumoniae arthritis and osteomyelitis with vitamin C deficiency in guinea pigs. Lab Anim Sci 38:192-194. Pregnancy Toxemia Guinea pigs are susceptible to both ketosis and true pregnancy "toxemia," or pre-eclampsia. Several factors are important in the development of ketosis, including age, sex, diet, obesity, fasting, exercise, parity, fetal load, and heredity. The combined effects of obesity and fasting during late pregnancy are especially important. It is thought that any stress may result in failure to eat, which accentuates pre-existing hypoglycemia associated with pregnancy and results in rapid mobilization of fat and consequent ketosis. Clinical signs of ketosis include anorexia, adipsia, weight loss of 12-18% within 96 hours, hypoglycemia, lipemia, ketonemia, ketonuria, urine pH 5-6 (normal is 9), clonic spasms of voluntary muscles, coma, and death (in 4-5 days unless interrupted by parturition). Golden JG et al. 1980. Experimental toxemia in the pregnant guinea pig. Lab Anim Sci 30:174-179. Seidl DC et al. 1979. True pregnancy toxemia (pre-eclampsia) in the guinea pig (Cavia porcellus). Lab Anim Sci 29:472-478. Torsion of Uterus or Stomach Three cases of torsion of the uterus and one of torsion of the stomach have been reported; pregnant guinea pigs may be prone to them. Kunstyr I. 1981. Torsion of the uterus and the stomach in guinea pigs. Z Versuchstierkd 23:67-69. Soft Tissue Mineralization Guinea pigs use cations rather than NH3 to neutralize excess acid excreted by the kidney. This may be why guinea pigs are particularly sensitive to levels of and balances among Ca, P, Mg and K, and why they are more susceptible to soft tissue mineralization than other rodent species. Clinical signs include poor growth, muscular stiffness (especially forelegs), abnormal gait, anemia, elevated serum P, and death. Mineral deposits occur in virtually any soft tissue except brain. Most common are skeletal muscle, heart, stomach, lungs, and foot pads. Sparschu GL, Christie RJ. 1976. Metastatic calcification in a guinea pig colony: a pathological survey. Lab Anim Care 26:434-443. Neoplasms Guinea pigs are said by some to have a lower than average frequency of neoplasms. According to a 1976 review, only 306 cases had been reported. Of these, 35% were pulmonary adenomas or adenocarcinomas, 22% were of hematopoietic origin, 15% were skin tumors, and 15% were from the reproductive tract. Andrews EJ, Shively JN. 1976. Intracisternal virus-like particles in two guinea pig mammary adenocarcinomas. Lab Anim Sci 26:607-609. Andrews EJ. 1976. Mammary neoplasia in the guinea pig (Cavia porcellus). Cornell Vet 66:82-96. Cook RA et al. 1982. Extraskeletal osteogenic sarcoma in a guinea pig. J Am Vet Med Assoc 181:1423. Ediger RD, Covatch RM. 1976. Spontaneous tumors in the Dunkin-Hartley guinea pig. J Natl Cancer Inst 56:293-294. Field KJ, Griffith JW, Lang CM. 1989. Spontaneous reproductive tract leiomyomas in aged guinea pigs. J Comp Pathol 101:287-294. Frisk CS et al. 1978. An ovarian teratoma in a guinea pig. Lab Anim Sci 28:199-201. Hong CC et al. 1980. Naturally occurring lymphoblastic leukemia in guinea pigs. Lab Anim Sci 30:222-226. Hong CC, Liu PI. 1981. Osteogenic sarcoma in 2 guinea pigs. Lab Anim 15:49-51. Hong CC. 1980. Spontaneous papillary cystadenocarcinoma of the ovary in Dunkin- Hartley guinea pigs. Lab Anim 14:39-40. Olson LC, Anver MR. 1980. Ovarian stromal sarcoma in a guinea pig. Vet Pathol 17:245- 247. Trahan CJ, Mitchell WC. 1986. Spontaneous transitional cell carcinoma in the urinary bladder of a strain 13 guinea pig. Lab Anim Sci 36:691-692. Wilson TM, Brigman G. 1982. Abdominal mesothelioma in an aged guinea pig (Cavia porcellus). Lab Anim Sci 32:175-176. Wolff A et al. 1988. Cervical lymphoblastic lymphoma in an aged guinea pig. Lab Anim Sci 38:83-84. Zwart P et al. 1981. Cutaneous tumors in the guinea pig. Lab Anim 15:375-377. Miscellaneous and General References Bendele AM, White SL, Hulman JF. 1989. Osteoarthrosis in guinea pigs: histopathologic and scanning electron microscopic features. Lab Anim Sci 39:115-121. Boot R et al. 1989. The 'normalization' of germ-free guineapigs with host-specific caecal microflora. Lab Anim 23:48-52. Boot R, Walvoort HC. 1986. Opportunistic infections in hysterectomy-derived, barrier- maintained guinea pigs. Lab Anim 20:51-56. Boot R, Walvoort HC. 1986. Otitis media in guinea pigs: pathology and bacteriology. Lab Anim 20:242-248. Griffith JW et al. 1988. Osseous choristoma of the ciliary body in guinea pigs. Vet Pathol 25:100-102. Hsiung GD et al. 1980. Viruses of guinea pigs: Considerations for biomedical research. Microbiol Rev 44:468-490. Jure MN, Morse SS, Stark DM. 1988. Identification of nonspecific reactions in laboratory rodent specimens tested by Rotazyme rotavirus ELISA. Lab Anim Sci 38:273-278. Keller LSF et al. 1987. Reproductive failure associated with cystic rete ovarii in guinea pigs. Vet Pathol 24:335-339. van Herck H et al. 1988. Dermal cryptococcosis in a guinea pig. Lab Anim 22:88-91. Wagner JE, Manning PJ (eds.) The Biology of the Guinea Pig. Academic Press, New York, 1976, pp. 121-135. Yamasaki K, Fukushima Y. 1986. Interstitial pneumonia in guinea pigs. Jikken Dobutsu 35:345-346.