DISEASES OF GUINEA PIGS

POLA 1999

Marti Hanes, DVM

Department of Lab Animal Resources

University of Texas Health Science Center-San Antonio

San Antonio, Texas 78284

210-567-6166

hanes@uthscsa.edu

General Features of Guinea Pigs

· nervous, will go off feed with any changes

· long gestation, dystocia, breed all year, will nurse other infants- good for rederivation

· precocial birth, wean early eat solid food at 3-4 days

· few viral infections

· major diseases: scurvy, respiratory tract infections, and enteric disease

· male dominated hierarchy, males will groom infants

· bite wounds from aggressive males, barbering of subordinates

· diurnal, copraphagic, not cache food, eat frequently, require constant source of water, and need training on sipper tubes

· indiscriminate defecation- water bowls, food dishes

· responsive to sound, startle, freeze, stampede

· vocalize, complex communication

Anatomic Features

· two inguinal nipples

· intact vaginal closure membrane

· large vesicular glands

· pubic symphysis under action of relaxin

· large adrenal glands

· long colon (60% length of rat)

· large tympanic bullae

· intracoronary collateral network

· open inguinal canals

· thick medial walls of pulmonary vessels

· cervical thymus

Hematology

· heterophils

· lymphocytes-large and small predominate

· Kurloff cells

Animal Models (Publications from last three years surveyed in Pub Med 5/99)

· Toxicology

· lung (allergy-latex, dust, anaphylaxis, asthma, inhalation-leather conditioner, toluene)

· skin (dermal, allergic, hypersensitivity, psoriasis, wound repair, thermal, poison ivy, military-mustard gas, euthymic hairless GP)

· cardiac and vascular (tetrodotoxin, implants, septic shock, antiarrhythmics, vasoconstriction)

· pharmaceutical( antifungal, antiviral, antibiotics, antianxiety, antihistamines, antioxidants)

· reproductive (embryology, teratology, neonatology, infertility, hormones, ethanol)

· intestinal (heavy metal, inflammation-ileitis, colitis)

· hepatic/pancreatic (lipid, diabetes, anesthetics-halothane, bile-free radicals, gallstones)

· ocular(myopia, conjunctivitis)

· auditory(noise, antibiotics )

· proprioception (balance, Meniere’s disease)

· nerve( amyotropic lateral sclerosis, EAE, spinal cord injury, epilepsy electrolytes, antinflammatories, MS)

· Surgery - Otolaryngology, cardiology, implants, mastectomy, transplantation, device infection

· Bone/Cartilage Disease - Osteoarthritis, Vitamins C, D, and A, rotator cuff, osteopenia

· Immunology - Viral, complement, IgE, asthma, autoimmune encephalitis, DHT

· Stress - Adrenocortical function, corticosteroids, renal hypertension, thermoregulation

· Hematology, Coagulation - Thrombosis, complement, eosinophilia, PAF

· Nutrition - Fatty acids, vitamins

· Neoplasia -Carcinogens-alfatoxin (liver), bracken fern (urinary bladder), reproductive

· Physiology - Cardiac, hearing, nerve conduction

· Infectious animal models

· Prions (Creutzfeldt-Jakob)

· Viral(Marburg/Ebola, Herpes-genital, LCM, Cytomegalovirus, Respiratory Syncytial Virus, Foot and Mouth Disease, equine morbillivirus [Hendra, Nipah], poliovirus, PIV-3,Venezuelan HF-Guanarito, Adenovirus 5, Pichinde)

· Bacterial (Staphlococcus, Borrelia, Moraxella, Legionella, Helicobacter, Serpulina, Leptospirosis, Pseudomonas, Mycobacterium, Streptococcus, Treponema, Corynebacterium, Yersinia)

· Chlamydial/Rickettsial (Coxiella, C. psittici-Inclusion conjunctivitis, urethritis)

· Protozoal (Trypanosoma, Cryptosporidia)

· Fungal/ Algae (dermatophytes-Trichophyton, pulmonary allergen-Penicillium, Aspergillus fumigatus , endocarditis)

· Helminths(Trichostrongyles, Onchocerca, Baylisascaris, Dictyocaulus)

· Arthropods (Triatoma)

Disease Differential List

· Diarrhea -Tyzzer’s, colibacillosis, salmonella, coccidiosis, Arizona sp, Citrobacter sp, coronavirus, clostridial typhlitis, clostridial dysbiosis, cryptosporidiosis

· Respiratory -Bordetella, S. pneumonia, S. zooepidemicus, Klebsiella, Pasteurella multicida, P aeruginosa, C freudii, S. aureus, heat stress, diaphragmatic hernia, pregnancy toxemia, gastric torsion

· Ptaylism - Malocclusion, hypovitamin C, heat stress, flurosis

· SQ Swelling - Abscess-(S. zooepidemicus, S. aureus, S. moniliformis, Y. pseudotuberulosis), neoplasia (leukemia)

· Dermatitis - Bite wounds, Trixascarus cavia, cryptococcosis, Staph, dermatophytosis, pediculosis, Chirodiscoides, Psoroptes.

· Otitis-Otosclerosis, Otitis Media - Often subclinical - caused by S.pneumoniae, S. zooepidemicus, Bordetella sp, and Pseudomonas,

· Mastitis - Sporadic, early lactation, not necessarily contagious. Blue breast is characterized by red to purple enlarged, firm, congested, edematous mammary glands. Lesions can vary from mild degeneration to necrosis of ductal epithelium with PMN infiltration in ducts and alveoli. Scattered cells occupy the interstitium. Chronic mononuclear cell infiltration with interstitial fibrosis and architectural obliteration will affect future usefulness of these animals as breeders. Isolates have included E. Coli, Klebsiella and S, zooepidemicus

· Conjunctivitis - Isolates have includes Streptococcus, coliforms, Staphlococcus and Pasteurella multocida, Listeria. Smears should be examined for Chlamydia.

· Infertility - Age, stress, flooring, estrogen in feed, bedding adherent to genitals, increased temp, nutritional deficiency, metritis, preputial dermatitis, segmental aplasia of uterus, cystic ovaries, perinatal death, abortion-stillbirth-(dystocia, Bordetella, Salmonella, Strep, CMV, birth asphyxiation, pregnancy toxemia).

· Death - Chilling, overheating, septicemia, toxemia, Salmonella, cecitis, enteritis, pregnancy toxemia, antibiotic reaction, pneumonia, volvulus of cecum or stomach, dystocia, dehydration, stuck foot in grate, fractured limb.

· Anorexia and/or Weight Loss - Neophobia, water deprivation, temperature, change in food, unpalatable food/improperly compounded, toxin ingestion, malocclusion, oral laceration, obesity, metabolic disease, renal failure, Vitamin C deficiency, infection, neoplasia, loss of cage mate, mechanical failure, territorial behavior-dominant male, amyloidosis with pododermatitis, protein deficiency, metabolic calcification, ectoparasitism, Urolithiasis.

· Reluctance to Move - Hypo Vitamin C, Bordetella, Salmonella, malnutrition, Vitamin E deficiency, Osteoarthritis, spinal trauma/fracture, dystrophy/myopathy.

I. BACTERIAL INFECTIONS

· Bordetella bronchiseptica - A small gram negative rod, important disease causing organism in the upper respiratory tract of several species with apparent interspecies transmission. Isolates do not appear to have differences in virulence. Affects guinea pigs of all ages, following intranasal inoculation. Severe disease and mortality are most common in young guinea pigs in the winter. Guinea Pigs may harbor inapparent infection. The number of subclinical nasal shedders may be quite high. Rabbits should not be housed with guinea pigs. The organism has an affinity from ciliated respiratory epithelium. Pregnant sows may abort, produce stillborn or die. At necropsy, there is mucopurulent to catarrhal exudate in the nasal passages, and trachea. Pulmonary consolidation and hemorrhage are usually anteriovental and may involve all lobes. Mucopurulent exudate in the airways and tympanic bullae may occur. Pleuritis or pyosalpinx may be seen. Microscopically, acute to chronic suppurative bronchopheumonia with heterophilic infiltration, obliteration of the normal architecture and fibrinous exudate may be present. The organism can be cultured on blood agar from the respiratory tract, tympanic bullae or affected uterus. Differential diagnoses must include Streptococcus, Klebsiella, Staphlococcus, or previous Freud’s adjuvant administration (chronic interstitial fibrosis and granulomatous pulmonary inflammation).

· Salmonellosis - S. typhimurium , S. enteritidis, S. dublin are important and severe sporadic diseases of guinea pigs. Transmission is by ingestion of contaminated food, water or bedding. The conjunctiva is a portal of entry in guinea pigs. Salmonella are frequently in a carrier state and are intermittently shed in the feces, making elimination of the pathogen difficult. Predisposing factors include youth or old age, stress of pregnancy or weaning, nutritional deficiencies, disease, genetics, serotype, environment (winter) and experimental stress. Salmonellosis may be enteric, systemic, epizootic, enzootic and zoonotic. Sporadic outbreaks with high mortality in guinea pigs may approach 100%. Clinical signs are often non-specific: per acute:death, acute: depression, rapid deterioration, lethargy, dyspnea; in chronic disease see anorexia, weight loss, and rough hair coat, conjunctivitis, ocular discharge, general unthriftiness, small litters, abortion, and sporadic death. Diarrhea is variable, soft feces more common. Lesions of acute salmonellosis are similar to other animals and involve the liver, spleen, lymphoid tissues and intestine (enlargement, congestion, focal necrosis), the spleen may be massive. Increased gas and fluid contents in the gastrointestinal tract. Pregnant animals may have a purulent metritis. Lesions in subacute to chronic cases may demonstrate yellow necrotic foci in the liver and viscera with hyperemia. Peyer’s patch hyperplasia, hepatomegally, and splenomegally. Microscopically, multifocal necrogranulomatous hepatitis, splenitis and lymphadenitis with the areas of necrosis are surrounded by mononuclear cells and neutrophils (paratyphoid nodules). Diagnosis by culture of mesenteric lymph nodes, conjunctiva, feces, cecum, or aborted material (SS agar, MacConkey’s or others). Isolation should be serotyped, because non-pathogenic species exist. Control is depopulation, sanitation and restocking because of the carrier state. Guinea pigs do not respond to antibiotics well and may develop enterotoxemia. DDX: clostridium enterotoxemia, yersinosis, Tyzzer’s and pneumococcal septicemia. Zoonotic and interspecies transmission potential is high.

· Cervical Lymphadenitis (Streptococcus zooepidemicus) - beta-hemolytic, G+, encapsulated, Lancefield Group C. Asymptomatic inhabitant of the upper respiratory tract-Transmission through skin wounds,bite wounds, aerosol or genital. Oral cavity abrasions caused by coarse plant feeds and conjunctiva are commonly implicated. After penetration, the organism drains to the local lymph nodes. Uni-or bilateral swelling at angle of jaw is referred to as “lumps” or cervical lymphadenitis, but may be misleading because other lymph nodes may be affected and a similar appearance may be caused by agents, such as Streptobacillus moniliformis, Yersinia pseudotuberculosis, Salmonellae (S. linate,) other Streptococcus sp., Zygomycetes, and Cavian leukemia. Grossly, see encapsulated and abscessed ventral and cervical lymph nodes and abscesses in various organs.The purulent exudate is white to yellow in color. Septicemia and acute fatal pneumonia occur in the epizootic form. Torticollis (head tilt) may occur due to otitis media and otitis interna. Nasal Discharge, ocular discharge, dyspnea and cyanosis may develop. Chronic infections can be exacerbated by stressors. At necropsy, infection may vary from an acute fatal septicemia to a chronic suppurative process in the lymph nodes, thoracic and abdominal viscera, uterus, and ears. Microscopic evidence of pneumonia, pleuritis, myocarditis, pericarditis, and peritonitis, otitis media, nephritis, arthritis, and cellulitis will be seen characterized by necrotizing suppurative inflammation or fibrinosuppurative inflammation. Chains of gram positive cocci may be seen in direct smears or tissue sections. Culture on blood agar from abscesses, heart blood or lungs will yield small beta-hemolytic mucoid colonies. Systemic antibiotics such as enrofloxacin or chloramphenical are effective. Abscesses may be drained and flushed. Affected animals should be removed from the colony until the abscesses have drained and healed. In epizootic cases, depopulation is advised. Scratch injection with ATCC 12960 (swine) has provided some immunity. Apparently S. zooepidemicus is strictly an animal pathogen.

· Streptococcus (Diplococcus) pneumoniae - Caused by a lancet-shaped, gram positive encapsulated coccus in chains and pairs. Capsular type 19 and less frequently type 4 have been isolated from guinea pigs. The disease seldom occurs in well-managed facilities, and may be carried as an inapparent infection in the respiratory tract in up to 50% of animals. Aerosol transmission, mostly during the winter months, with young and pregnant sows at greatest risk. Other predispositions include change in environmental temperature, poor husbandry, experimental procedures and inadequate nutrition. During outbreaks, death, stillbirths and abortions occur. Pneumococci may activate the alternative complement cascade, and are protected from phagocytosis due to the polysaccharide capsules. At necropsy, fibronopurulent pleuropneumonia, pericarditis and pulmonary consolidation are apparent. Histologically, an acute fibrinosuppurative bronchopneumonia is present with thrombosis of pulmonary vessels. Infiltrating cells may be elongate and form palisading patterns in affected airways. Splenitis, fibrinopurulent meningitis, metritis, lymphadenitis with focal hepatic and ovarian abscessation have been reported. Guinea pigs with borderline vitamin C deficiency may develop S. pneumoniae associated suppurative arthritis and osteomyelitis. Direct smears will yield G+ alpha- hemolytic, diplococci, blood agar to culture, and is a little fastidious.(optochin disk on blood agar) DDX: Bordetella sp., S. zooepidemicus. Serotypes are same as seen in human, interspecies transmission is suspected.

· Staphylococcus sp. - Ulcerative pododermatitis and acute staphloccocal exfoliative dermatitis are associated with coagulase positive staphylococcus.

· Pododermatitis - Caused by infection subsequent to trauma, wire cage bottoms and lack of appropriate sanitation. Bumblefoot may also be caused by obesity, rough cage bottoms, unsanitized floors. Most lesions are chronic .The contact surface of the forefeet are swollen, painful and encrusted with necrotic, exudative tissue and clotted blood and /or crust. Microscopically, lesions are fibrotic pyogranulomatous inflamation. Amyloidosis has been temporally associated with advanced cases. Isolated cases of pneumonia, mastitis and conjunctivitis have been seen.

· Dermatitis - Seen in strain 13 guinea pig, and seen in young pigs born to affected dams. It is characterized by alopecia, erythema of the ventrum, with exfoliation. Skin lesions regress in two weeks, with hair re-growth. At necropsy, there is erythema, scabbing, cracks in the epidermis and hair loss. Histologically, there is marked epidermal cleavage parakeratotic hyperkeratosis and minimal inflammatory response. Possible interspecies transmission.

· Clostridium piliforme, Bacillus piliformis - Tyzzer’s lesions are usually confined to the gastrointestinal tract in young guinea pigs. Multifocal gray foci on the liver, rough hair coat, lethargy, watery diarrhea, death. Large numbers of spirochetes were associated with clostridial organisms near lesions. Experimental inoculation of young animals produced lesions in intestine and liver by four days. Edematous, hemorrhagic, ulcerative, or necrotizing ileitis and typhlitis with transmural involvement and fluid contents. Hepatic lesions when present are characterized by focal coagulative necrosis in periportal regions with variable numbers of PMN’s. Warthin-Starry and Giemsa stains will demonstrate the organism. Interspecies transmission.A carrier state seems to be suggested by outbreaks appearing after stress.

· Clostridium difficile (Antibiotic toxicity and dysbacteriosis) - A fatal enterocolitis caused by clostridial toxin after administration of narrow spectrum drugs. Clindomycin, lincomycin, erythromycin, penicillin, bacitracin, dihydrostreptomycin, and ampicillin cause disease 1-5 days after administration. Profuse diarrhea with high mortality, after rapid kill-off of gram positive normal flora. For example, after IM injection of 50,000 IU penicillin there was a 100X decrease of G+ within 12 hours, followed by a 10,000,000X increase in G- bacteremia due to E. coli. In addition, some AB are excreted in the bile. This can be prevented by using a broader spectrum antibiotic. Oddly, C. difficile is usually susceptible to Penicillin in vitro. At necropsy, the cecal mucosa is edematous, hemorrhagic and distended by gas and bloody fluid. The terminal ileum demonstrates hyperplasia of the mucosa, with mononuclear cell infiltrates in the lamina propria. Cecal epithelial degeneration with sloughing, edema of the lamina propria, and leucocytic infiltration. Assay of cecal contents for C. difficile, this syndrome may occur in the absence of history of AB administration. Safer AB: chloramphenicol, enrofloxicin, trimethoprim-sulfa, and aminogycosides. Rule out other common causes of GIT disease.

· Klebsiella pneumoniae - Patterns of epizootic septicemia and pneumonia with pleuritis, pericarditis and splenic hyperplasia are reported. Culture of Klebsiella sp . is diagnostic.

· Citrobacter freundii - An epizootic of Citrobacter septicemia with pneumonia, pleuritis, enteritis with isolation of the organism was reported.

· Clostridium perfringens - Acute fatal typhlitis, sporadic. The cecum contains fluid, gas and ingesta. Micro-degeneration and sloughing of enterocytes, necrosis of adjacent submucosa, C. perfringens, spirochetes and other bacteria have been isolated and causally associated.

· CAR Bacillus - “Cilia associated respiratory bacilli”, “gliding bacteria”, filamentous, 0.2u-6-8u long trilaminar cell wall, exacerbates other respiratory disease. Guinea pigs are not very susceptible. Direct contact. No gross lesions with rat origin bacteria.

· Campylobacter-like Organism - Segmental epithelial hyperplasia of the duodenum was seen in steroid treaded guinea pigs. An outbreak with diarrhea, weight loss and mortality, yielded affected animals with adenomatous hyperplasia in the ileum and jejunum. Similar to the changes seen in hamster Campylobacter-associated disease with organisms in the immature crypt epithelium on EM.

· Pseudomonas aeruginosa - Pulmonary botryomycosis with sulfur granules present in the focal suppurative lesions was reported.

· Corynebacterium sp. - C. kutcheri, one report, mostly a disease of mice and rats, possibly an interspecies exposure. Has caused chorioamnionitis in man.

· Yersinia pseudotuberculosis - Experimental disease can be produced, but spontaneous disease is rare. In the acute form, small cream colored nodules are seen in the terminal ileum and cecal intestinal wall with enteritis and ulceration of the mucosa. In the subacute to chronic forms, miliary to caseous lesions may be present in the mesenteric lymph nodes, spleen, liver and lung. Culture is diagnostic.

· Streptobacillus moniliformis - Similar to Streptococcal infections, suppurative creamy to caseous exudate, lesions culture positive for S. moniliformis include cervical lymphadenitis, abscessation, and pyogranulomatous pneumonia.

· Listeriosis (Listeria monocytogenes ) - Unilateral or bilateral conjunctivitis with serous lacrimation to purulent ulcerative keratoconjunctivitis with neovascularization. Diffuse moderate to severe inflammatory infiltrate composed of neutrophils and few lymphocytes and monocytes expand the cornea and present in the superficial bulbar and palpebral conjunctiva. Lacrimal gland necrosis and inflammation, no other lesions noted. Listeria is a gram+ aerobic nonspore-forming bacterium widely distributed in silage and hay.

II. RICKETTSIAL/CHLAMYDIAL INFECTIONS

· Chlamydia psittici-Guinea Pig Inclusion Disease (GPIC) - Spontaneously occurring conjunctival infection due to Chlamydia psittici (member of the psitticosis-lymphogranuloma-trachoma group). It is widespread among conventional colonies, frequently asymptomatic, but may be demonstrated with conjunctival smear stained with Giemsa. Young, 4-12 week old animals, are most susceptible with most adults seopositive. May also see rhinitis or genital tract infection, photophobia. There may be abortions or respiratory tract infections with concurrent immunosuppression and/or Streptococcus or Bordetella. Transmission by direct contact to feces, saliva, nasal secretions, and cervically by pregnant sows. Grossly, the conjunctiva may be erythematous with serous or exudative ocular discharge. Conjunctival scrapings and smears contain sloughed cells, heterophils and lymphocytes. Antigen is demonstrable with specific antibody and IFA.and stained smears with identification of inclusion bodies Self-limiting disease (three-to-four weeks) with no residual damage. DDX: Streptococcus zooepidemicus, Coliforms, Staph, Pasteurella, Listeria. Not proven to be contagious to humans.

III. VIRAL INFECTIONS

· Cytomegalovirus (Herpesvirus) - Species specific. Natural infection in humans, primates, mice, rats and guinea pigs. Cells produce characteristic large intranuclear and intracytoplamic inclusion bodies. The infection may be subclinical,latent or persistent. Natural infection of guinea pigs is characterized by swelling of and lesions in the salivary glands, kidneys, and liver. Most will seroconvert within a few months. It is transmitted by exposure to infected saliva, urine or transplacentally. Replicaton and transmission of virus in salivary glands and secretions.Pregnant guinea pigs and immunosuppressed or inoculated animals develop more extensive lesions. Lymphoproliferative (lymphoid hyperplasia), mononucleosis-like syndromes and lymphadenopathy occurs in experimentally infected animals. Lesions are often found as incidental lesions at necropsy. Primarily seen in the submaxillary salivary duct epithelium. Large eosinophilic intranuclear inclusions with marked karyomegaly and margination of nuclear chromatin in affected cells. Occasional small intracytoplasmic inclusions are seen in ductal epithelial cells. There may be a concurrent periductal mononuclear cell infiltrate around infected ducts. In acute systemic infections, interstitial pneumonia with necrosis and inclusions can be seen in the liver, kidney, lung, spleen and lymph node. Useful animal model.

· Guinea Pig Adenovirus Infection - Seen in the United States and Europe. Low morbidity but high mortality in infected animals. Usually related to experimental manipulation with impairment of the immune system. Grossly, consolidation of the cranial lobes of the lung are seen. Necrotizing bronchitis, bronchiolitis with desquamation of the epithelial lining and inflammatory cell infiltration. Some airways will be obliterated by cell debris, WBC’s and fibrin.Pneumonia and necrotizing tracheitis may be present. Nuclei of respiratory epithelial cells often contain distinctive basophilic to amphophilic inclusions 7-15u in diameter. Electron microscopy reveals classic arrays. This virus has not been isolated, however, disease has been reproduced with cell-free filtrates.

· Coronavirus-like Infection in Young Guinea Pigs - Characterized by wasting, anorexia, diarrhea seen after arrival from vendor. Low morbidity and mortality. Acute to subacute necrotizing enteritis involving the distal ileum. Copious amounts of mucoid material present throughout the gastrointestinal tract. Blunting and fusion of the affected villi with synctial giant cells in the intestinal mucosa. Viral particles consistent with coronavirus seen on EM.

· Guinea Pig Herpes-like Virus (Herpesvirus) (Caviid Herpesvirus 2) - Isolated from primary kidney cell culture - does not produce disease in the natural host.

· Guinea Pig X-Virus (GPXV) (Herpesvirus) (Caviid Herpesvirus 3) - Originally isolated from leukocytes of Strain 2 pigs - experimental inoculation into Hartley Strain caused, viremia, focal hepatic necrosis and mortality - a possible complicating factor for research.

· Lymphocytic Choriomeningitis (LCM) (Arenavirus) - Mostly experimental disease in guinea pigs. Posterior paresis, liver and splen enlargement Lymphocytic infiltrates in meninges, choroid plexus, ependyma, liver, adrenal, kidney and lungs. Wide host range, exposure by inhalation, ingestion,intrauterine or through intact skin. DX viral antigen in tissue or section, by IFA, ELISA, MAP, Complicates research and is transmissible to humans, causing mild to moderate illness. Wild mice are a reservoir.

· Cavian Leukemia (Retroviridae, Type C Oncovirus Group, Mammalian Group) Widespread, spontaneous disease in inbred and outbred strains. Seen in young adults. Lymphadenopathy, rough hair coat, weight loss, ascending paralysis seen in clinical disease.Leukocytes vary from 50,000-250,000. Can be produced with transplanted cells and cell free extracts. Preponderance of cells are lymphoblastic in blood smear. Large lymph nodes in the cervical axillary and inguinal areas are seen with splenomegally and hepatomegally, affected tissues are swollen and pale. There is a moderate infiltration with obliteration of the normal architecture with lymphoblastic-type leukemic cells in the spleen, liver, bone marrow, lung, thymus, GIT-GALT, heart, eyes and adrenals. Model of viral associated Neoplasia.

· Other viruses: Serologic evidence of subclinical exposure: Sendai, Murine Poliovirus, Reovirus3, Pneumonia virus of mice, SV5

IV. MYCOTIC INFECTIONS

Dermatomycoses are most common; usually caused by T. mentagrophytes. Systemic mycoses relatively rare with only a few reports.

· Trichophyton mentagrophytes - Strain related susceptibility. Mortality rate in neonates approaches 100%. Spontaneous regression in adults, recurrence in sows at parturition. Related to environmental conditions: heat, humidity, spores in hair bedding and soil. Cutaneous lesions may first appear on the nose, other regions of the head and then on the sides and back. On gross examination, the lesions are circumscribed, erythematous, edematous, scaly with alopecia. Pustules are usually due to secondary bacteria. On microscopic exam, there is hyperkeratosis, epidermal hyperplasia, PMN infiltration, pustules in the epidermis and hair follicles. Arthrospores anf hyphae are seen in H&E, PAS or GMS. Wet preps with 10% KOH. Culture in Sabouraud’s dextrose. Very zoonotic. Cull and slaughter is advisable. Systemic griseofulvin may cause teratogenesis. Useful animal model.

· Zygomycetes sp.

· Aspergillus sp.

· Histoplasma capsulatum.

· Cryptococcus neoformans.

· Torulopsis pintolopesii- gastric yeast, normal flora, unaffected by ketoconazole

V. PROTOZOAN PARASITES

· Toxoplasma gondii - Naturally occurring disease rare under current housing practice. Infections are asymptomatic, multifocal hepatitis and pneumonitis, cysts in the myocardium, CNS. Can be passed in the milk. Infected through ingestion of Felid oocysts in food or bedding need to differentiate from E. cunculi.

· Encephalitozoon cuniculi - Infectious, are usually asymptomatic. Similar to E. cuniculi infections in other animals, multifocal granulomatous encephalitis and interstitial nephritis. Glial nodules, perivascular lymphoplasmacytic cuffing in the neuropil and meninges. Obligate intracellular protozoa, incidence varies from 25-95%. Becomes clinical with stress or immunosuppression. Hematogenously spread via macrophages, selectively parasitizing vascular endothelium, especially brain and kidney life cycle 3-5 days. Gross-Kidney - variably severe multiple white pinpoint foci, indented gray area over cortical surface. Micro mild to moderate granulation to chronic interstitial nephritis and tubular dilation. The granulomas are principally in the epithelial cells of collecting tubules. Organisms are most abundant in early stages of disease which complicates research.

	T. gondii	E. cuniculi
H&E	Moderate stain	Poorly stained
PAS	Cyst wall positive	Cyst wall negative
GRAM	Gram nothing	Gram positive
Pseudocyst	Small 60u	Large 120u
Spores	Not	Birefringent
Giemsa	Granulated cytoplasm	Light blue cytoplasm
Iron Stain	No stain	Stains black
Fatal to Mice	Is fatal	Not fatal

· Klossiella cobayae - “non-pathogenic”-Infects kidneys of guinea pigs. Organisms form schizonts in glomerular endothelial cells that are 8-12u and multinucleated. Within the tubular epithelium at the corticomedullary junction and medulla are variably sized, irregularly round 12-75u diameter vacuoles that enlarge the cells and compromise the tubular lumen. Microgametes and macrogametes, sporoblasts and sporocysts are seen. Generally an incidental finding, tubular epithelial cell regeneration with variable amounts of lymphocytes and plasma cells in the interstitium.

· Giardia caviae - A flagellate in the small intestine. Adheres to surface of epithelium and apparently causes no clinical signs or lesions.

· Cryptosporidium wrairi - A recognized pathogen, may be subclinical. In small intestine, clinical infection occurs in juveniles. Infection rate of 30-40% are typical. Causes greazy rough hair coat, lethargy, diarrhea, weight loss, emaciation, morbidity may range from 0-50%. At necropsy, animals are thin and potbellied, with perineal fecal staining. Small intestine will be hyperemic and will contain watery material and little food. Acute edematous lesions seen in the jejunum, anterior ileum and cecum. Hyperplasia of the crypt epithelium, edema of the lamina propria and leucocytic infiltration. Necrosis and sloughing of enterocytes occur at the villar tips. In emaciated animals with chronic lesions, there is villar atrophy and fusion, metaplasia and flattening of villar enterocytes. Eosinophilic inflammation may be present.Organisms are very small, round, intracellular, but extracytoplasmic with hold fasts, present within the brush border of enterocytes. They can be seen inmucosal scraping or paraffin embedded tissue with H&E but PAS is popular. Transmission by oocysts in water, food, fomites. E. coli has been associated with clinical cases of C. wrairi.

· Eimeria caviae - Typical Eimerian life cycle. Should not be a problem in a well-managed colony. Following ingestion of sporulated oocysts, sporozoites penetrate the intestinal mucosa, schizogeny detectable in seven days, diarrhea at 10-13 days, severely affected will have diarrhea before oocytes sporulate. Weaning and seasonal fluctuation. At necropsy the colonic wall is hyperemic, the mucosa congested and edematous, with petechial hemorrhages, and gray-white nodules. Ingesta may be flecked with blood. Chronically, colonic hyperplasia, edema of the lamina probria, infiltration with PMN’s and mononuclear cells, microgametes and macrogametes in large numbers. DX see organisms in mucosal scraping, fecal float, histology. Rx: coccidiostats.

· Balantidium caviae - Ordinarily non-pathogenic but can be a secondary invader. Organisms are large, have cilia in variable number of rows, have a large ovoid to ellipsoid macronucleus, have a smaller micronucleus, have one contractile vacuole, and have a bean-shaped cytostome. Seen in fecal smears or in histo sections.

· Entamoeba caviae is non-pathogenic, however experimental infection with Entamoeba histolytica provides an appropriate animal model. Produces liver abcesses, bloody diarrhea, intestinal pain, fever. Presence of trophozoites containing erythrocytes indicative of pathogenic strains. Amoeba mimic macrophages and heptocytes in histology sections. Lesions are flask shaped ulcers progressing to transmural abcesses. Liver abcesses have minimal inflamitory reaction.

· Tritrichomonas species are incidental common findings-oval pear shaped eosinophilic flagellates, non pathogenic.

VI. HELMINTH PARASITES

· Nematodes Paraspidodera uncinata (Cecal Worm) - Found in cecum and colon; rarely produces clinical disease. Is not common. Is 2-5mm long and has a direct life cycle of 65 days, with no migration beyond the intestinal mucosa.Shed eggs in fece, thick wall ascarid type egg.

· Trematodes Fasciola sp. - Has been reported several times and produced severe liver damage. Infection associated with feeding greens contaminated with metacercariae.

VII. ARTHROPOD PARASITES

· Mallophagia - Large biting, chewing lice cause pediculosis, pruritis, rough hair coat, alopecia in heavy infections.

· Gyropus ovalis - The oval guinea pig louse (uncommon) wide head -1.0-1.2mm long.

· Gliricola porcelli.- The slender guinea pig louse (common) thin head -1.0-1.5mm long.

· Chirodiscoides caviae - Relatively common in commercial supplies, lab facilities and pet animals; can bee seen moving around especially in the lumbar region. Non-burrowing, pretty harmless. Usually seen in a group of 3-2 immature males and one more mature female easily overlooked unless heavy infestation (>200/cm3) pruritus with alopecia. Magnification exam for diagnosis.

· Trixacarus caviae - Burrowing sarcoptic mange, intense pruritus, widespread alopecia, and hyperkeratosis. Severe dry, scaling, crusting, dermatitis, especially near neck and shoulders, inner thighs, abdomen. Probably some historical confusion with Sarcoptes and Notodres. Self-mutilation, some mortality. Hematological changes associated with intense marked pruritis, include heterophilia, monocytosis, eosinophilia and basophilia. Flaccid paralysis and convulsions have been noted, vigorous scratching has lead to seizures. Microscopically-paraffin embedded specimen see epidermal hyperplasia, orthokeratosis, parakeratosis, irregular burrows in stratum corneum contains mites and eggs. Spongiosus, PMN infiltration, hair follicles not usual. 10% KOH mites and eggs. Human contacts may experience urticaria. TX: ivermectin.

· Psoroptes cuniculi - Rabbit ear mites may affect guinea pigs.

· Demodex caviae - One report; no clinical signs.

· Mycoptes musculi and Notodres muris - probable interspecies infection, not common.

VIII. METABOLIC/ AGE-RELATED DISEASES

Scurvy (Vitamin C Deficiency) - Only primates, guinea pigs, red vented bulbul birds, channel catfish and Indian fruit-eating bats are known to require a dietary exogenous ascorbic acid. Ascorbic acid is essential in the hydrolase reaction for formation of hydroxyproline and hydroxylysine in the collagen molecule. Lack of l-gulonolactone oxidase in the glucose to Vitamin C pathway. Connective tissue cells don’t produce collagen at a normal rate, with deficient or defective production of interosseous matrix. Vitamin C is also necessary for the catabolism of cholesterol to bile acids. In scurvy, epiphyseal cartilage persists, bone formation is suppressed. The cartilage lattice lengthens but is not replaced by bone. The resultant structure is very susceptible to trauma, resulting in multiple microfractures. Increased capillary fragility results from increased intercellular space between endothelial cells, vacuolar degeneration of endothelia and depletion of subendothelial collagen. Increased Prothrombin time, increased susceptibility to bacterial infection (especially Strep pneumonae) impaired macrophage migration, decreased phagocytosis of PMN’s. Clinically, guinea pigs have swollen hind limbs, and move with great difficulty. Increased vocalization (due to pain when moving). Anorexia, weight loss, delayed healing of wounds. Death in 2-3 wks due to starvation or secondary bacterial infection. At necropsy, there is enlargement of the osteochondral junctions with hemorrhage into the soft tissues. Especially in periarticular regions of hind limbs. Animals are thin and unkempt, with variable diarrhea. Variable blood in feces, ecchymosis in the urinary bladder and adrenals enlarged. Microscopically persistence of irregular epiphyseal cartilage evident in young animals, microfractures of cartilaginous spicules and hemorrhage. Proliferation of mesenchymal cells in periosteal regions and medullary cavity with displacement of BM hematopoeitic cells. May be aggregates of pink material between cells. Dental abnormalities occur: fibrosis of the pulp and derangement of odontoblasts. Subclinical hemosiderin laden macrophages in the lamina propria of the intestine. Severe skeletal abnormalities create a locomotor problem. Requires 5-10mg/kg daily, pregnant sows require six times that.

Myopathies

· Myopathy/Myositis - Necrotizing with necrosis of myofibers and leucocytic infiltration, loss of cross striation, multinucleated strap cell formation, variable mononuclear cells.

· Nutritional Muscular Dystrophy - Associated with Vitamin E and Selenium deficiency. Depression, conjunctivitis, spontaneous hind limb weakness, marked decrease in fertility. May die within one week of onset. Elevation of CPK. Marked pathology - coagulative necrosis, hyalinization of myofibers, fragmentation, increased basophilia, rowing of nuclei (regeneration) not mineralization, testicular degeneration later with Vitamin E deficiency. RX: tocopherol.

· Myocardial/Skeletal Muscular Dystrophy with Mineralization - Poorly understood, multifocal mineralization, may be seen as an incidental finding, especially in hind legs. May be asymptomatic, multifocal mineral with minimal inflammatory response, myocardial degeneration with mineral occasionally seen. In chronic lesions, will get mineral and fibrosis. There may be a genetic component.

· Metastatic Calcification - Seen most often in guinea pigs over one year of age. Muscle stiffness, untriftiness, renal insuffiency, mineral deposition may be confined to soft tissues around elbows and ribs, or may be widespread and include mineralization of lungs, trachea, heart, aorta, liver, kidney, stomach, uterus, and sclera. Dietary factors, possibly low magnesium and high phosphorus . High Ca/PO4 appear to interfere with Mg absorption. Rabbit food contains an excess of Vitamin D. Guinea pigs require more folic acid than rabbits. Use von Kossa or Alizarin stain for mineral in tissues. May be seen as an incidental finding in soft tissues.

Pregnancy Toxemia-Two different forms with similar clinical presentations. Both occur in advanced pregnancy with depression, acidosis, ketosis, proteinuria, ketonuria, and lowered urinary pH to 5-6. Pregnancy in guinea pigs has been referred to as a “parasitism of staggering proportions”.

· Fasting Metabolic Pregnancy Toxemia - Nutritional - OBESE sows, last two weeks of pregnancy, especially second pregnancy. Uterine contents are frequently 50% of non-pregnant weight. Stress factors: shipping, change in feeding, cabbage deprivation. Low blood sugar, ketosis, hyperlipemia, comatose and die in 5-6 days. Necropsy: animals have abundant fat with marked fatty infiltration in the liver, kidneys, adrenals, even in vessels stained with fat stains. Caused by reduced carbohydrate intake and mobilization of fat as an energy source.

· Circulatory/Toxic Pregnancy Toxemia (pre-eclampsia) - Uteroplacental ischemia occurs due to compression of the aorta caudal to the renal vessels by the gravid uterus. This results in a significant reduction of blood pressure in the uterine vessels, with placental hemorrhage, necrosis, thrombocytopenia, ketosis, and death. On micro, there will be leucocytic infiltration, multifocal periportal liver necrosis, nephrosis, and adrenocortical hemorrhage. This has been reproduced experimentally. Animal model.

· Diabetes Mellitus - Spontaneous disease with no clinical signs early in the disease. Onset three months, hyperglycemia, glucouria, rarely ketonuria, reduced fertility. Frequently, animals introduced into the colony will become diabetic, suggesting an infectious agent, not identified. Micro, there is vacuolation and degeneration of the beta cells in the islets of Langerhan’s with fatty infiltration of the exocrine pancreas and fibrosis of the vascular stroma. Glomerular tufts demonstrate thickened basement membranes with sclerosis in advanced cases.

· Segmental Nephrosclerosis - Common in aged (>1yr) guinea pigs, characterized by small lumpy kidneys with clinical signs of renal failure. Weight loss, edema, polyuria, polydipsia, and proteinuria. Irregular, pitted renal cortices. Possibly related to autoimmune disease, infectious agents and vascular disease. Resulting from focal ischemia and fibrosis. Spontaneous deposits of IgG and complement (C3) were demonstrated along the mesenchymal and peripheral glomerular basement membrane. Accelerated disease is seen in animals fed high protein diets. Elevated blood pressure and renal hypertension has been noted. At necropsy there are multiple granular pitted areas on the renal surface. Pale streaks extend down the cortex to the medulla in advanced cases. Microscopically, segmental to diffuse interstitial fibrosis with distortion of the normal architecture are seen. Mostly, the convoluted tubules and loops of Henle are involved. Tubules are lined by poorly differentiated cuboidal to squamous epithelium. Scattered tubules contain variable degrees of proteinaceous material and cell debris. There is senescence of individual glomeruli with fibrosis which may become extensive. There may be scattered foci of lymphoplasmacytic inflammation, medial hypertrophy of the renal vessels and endothelial hyperplasia. There may be increased BUN and creatinine values with non-regenerative anemia and low urine specific gravity.

· Osteoarthritis/ osteoarthrosis- Spontaneous and induced by surgical partial medial meniscectomy. Lameness unilateral and bilateral, reluctant to move, joint enlargement. Moderate to severe changes of the tibial plateau, more severe medial, characterized by chondrocyte and proteoglycan loss in the superficial and middle zone of the articular cartilage and proliferation of subjacent chondrocytes to form clones with fibrillation of hypocellular matrix. Also affects medial femoral condyle and meniscus, with tibial and femoral osteophytes. Synovial changes are characterized by increased mature fibrous connective tissue, mild synoviocyte hyperplasia with occasional papillary projections. Inflammatory cell infiltrate may not be present despite marked degenerative changes. Bone marrow may get replaced by fibroblasts, adipose tissue, and foci of metaplastic cartilage may be present. Animals normal may be normal at 61 days of age, severe arthrosis by 18 months. Hartley strain.

IX. NEOPLASIA

True neoplastic lesions are rare, usually found in animals over three years of age. A serum factor, possibly asparaginase, has been demonstrated to have anti-tumor activity. Foa Kurloff cells inhibit transformed human epithelial cells in vitro.

· Lung-Pulmonary/bronchogenic papillary adenoma (35%): small white circumscribed, visible - papillary structures lined by a single layer of hyperchromatic cuboidal epithelium. Malignancy is rare.

· Skin and subcutis: trichofolliculoma, sebaceous adenoma, penile papilloma, lipoma, fibrosarcoma, fibroma, carconoma.

· Uterus: leiomyoma (25%), fibroma, myxosarcoma, leiomyosarcoma.

· Ovaries: cystic rete ovarii (hormonal imbalance associated with leiomyosarcoma), teratoma.

· Endocrine: adrenocortical adenoma.

· Mammary: fibroadenoma, adenocarcinoma in males and females with mets to lymph nodes.

· Hematopoietic- Cavian Leukemia.(Strain 2)

X . UNIQUE AND MISCELLANEOUS CONDITIONS

· Kurloff Body - A cytoplasmic inclusion found in a mononuclear leukocyte called a Kurloff cell. It is unique to guinea pigs. In the non-pregnant guinea pig, the cells are located primarily in the sinusoids of the spleen, and in the stromal tissues of the bone marrow and thymus, and not normally in lymph nodes. The cells are rare in fetuses and neonates, but are common in adults, especially females. Their numbers increase during pregnancy and after exogenous estrogen treatment in both sexes. The bodies are round to oval, usually 1-8 microns in diameter, and are initially granular and later more finely fibrillar to homogeneous within a vacuole. They are PAS-positive, stain positive for fibrinoid material by the Lendrum stain and are thought to be secreted by the cell itself. It is interpreted to be composed primarily of mucopolysaccharides and glycoprotein associated with a protein polysaccharide material. On ultrastructure, the inclusions are membrane bound, and other cytoplasmic organelles in these cells are consistent with secretory activity. Large numbers of cells may be present in the placental labyrinth of pregnant sows. Kurloff cells have been shown to release inclusion material into the fetal endothelium and trophoblast. In vitro, the material has a toxic effect on macrophages. Kurloff cells may have a role in preventing maternal rejection of the fetal placenta, creating a barrier separating fetal antigens from immunologically competent maternal cells. These cells have been misinterpreted as lupus cells.

· Rhabdomyomatosis (Nodular Glycogen Infiltration) - Occasionally observed as an incidental finding in guinea pigs of various ages. In the past it was considered a degenerative lesion or a “blastemoid” tissue malformation. However, it is now considered to be a congenital disease related to a disorder of glycogen metabolism. Occasionally, larger lesions may appear grossly as pale pink, poorly defined foci or streaks. Rhabdomyomatosis may be seen most frequently in the left ventricle, but has been reported in any region. The lesion consists of a spongy network of enlarged, vacuolated myocardial cells supported by a loose network of delicate fibrils. The myocyte cytoplasm is abundant. The nucleus is central or peripheral. The cytoplasm may consist of pink fibrillar to granular material radiating from the nucleus (spider cells) or may have an abortive striated appearance. Vacuoles are round to polygonal and contain abundant glycogen (PAS positive) that is washed out during processing. Glycogen can be demonstrated in alcohol fixed specimens. There may be displacement and flattening of myocyte nuclei in affected fibers. It is considered an incidental finding and normally does not compromise cardiac function. This occurs also in swine, cattle, dogs, and man.

· Perivascular Lymphoid Nodules in Lung - Aggregates of lymphocytes in the adventitia of pulmonary vessel may be seen in a variety of stains and can be seen in young guinea pigs as early as five days. Very common. Usually seen around smaller branches of pulmonary arteries and veins. They appear to enlarge with age. Germ-free animals usually do not have these, at least up to three months of age. May be grossly visible as circumscribed pale, pinpoint up to 0.5mm subpleural foci. May be mistaken for granulomas created after SQ injection of Freud’s adjuvant.

· Osseous Metaplasia - Occasionally seen in guinea pigs, hamsters and rats. No clinical significance. May occur anywhere, but lung is common site and less so in kidney. Have seen plates of bone with bone marrow in the eye. Spicules are composed of dense lamellar bone with varying degrees of calcification. There is usually no reaction in adjacent alveoli. Large numbers of foci with bone marrow have been seen in X-irradiated guinea pig. On microscopic, concentric to eccentric aggregates of small arteries and veins. There may be focal to diffuse infiltrates in the alveolar septa of some animals. Most animals are free of these lesions. Airways and alveoli are clear. On electron microscopy, the lymphocytes have normal morphology and no virus.

· Alopecia - Frequently see thinning of hair in young animals at time of weaning; is associated with the period of transition between loss of baby fur and appearance of more coarse guard hairs. May be due to hairpulling, barbering,nutritional stress, hormones. Seen in sows in late pregnancy; is thought to be due to reduced anabolism of maternal skin associated with the rapid increase in fetal growth. The condition worsens with subsequent pregnancies. Nutritional (protein deficient <15% Crude Protein) and genetic factors are also involved and affect degree of alopecia. May also be caused by barbering, rough surfaces in cages or infections. Culling the most severely affected breeders reduces severity of alopecia.

· Cystitis and Urolithiasis (urinary calculi) - Stones occur anywhere in urinary tract and vary in size from sand to stones. Usually are calcium and magnesium carbonates and phosphates. Age, sex and immunosuppresion are related to development. E. coli cystitis in breeding females causes a thickening of the bladder mucosa, congestion, intramural/intralumenal hemorrhage, leukocytic infiltration in the submucosa, occasionally with desmoplasia, ulceration, PMN’s. May be the initiating factor or secondary to uroliths in the urinary bladder.

· Cystic Ovaries(cystic rete ovarii, serous cysts) - Usually seen in sows over one year old. Thin walled, fluid filled, fluctuant cysts up to 2cm in diameter and contain clear fluid. Variable size, lined by low cuboidal to columnar epithelial cells. Solitary cilia or tufts of cilia are present on the lumenal surface . There may be marked compression of ovarian tissue. Associated with cystic endometrial hyperplasia, mucometra, endometritis and fibroleiomyomas.

· Trophoblastic Giant Cells - Derived from the outermost layer of the fetal placenta (trophoblast) which is in direct contact with the maternal blood supply. (The guinea pig has a labyrinthine hemomonochorial placenta in which there is a single trophoblast layer forming a continuous syncytial layer.) These cells have remarkable migratory activity and can migrate out into the myometrium.

· Embryonic Placentoma (deciduoma)A multi-layered transitory growth of parthenogenic origin that occurs within the ovary of the young female, the placentoma is resolved by fibrosis. Regresses after 12-21 days of pseudopregnancy. Contins 6 regions. The mesometrial region (decidua basalis) consists of both spiny mesometrial cells and granulated metrial gland cells. A typical GMG cells are large (40u), frequently binucleate, with eosinophilic, intracytoplasmic granules (PAS+, diastase resistant), suspected to be bone marrow derived.

· Gastric Dilation- Acute, occurs sporadically, frequently affected animals are found dead with no previous indication of illness. Gastric volvulus will demonstrate 180 degree.

· Cecal Torsion - Acute death, displaced cecum distended with fluid and gas, wall may demonstrate edema and hemorrhage.

· Colonic Intussusception - Stress, dehydration, straining, hemorrhage protrusion of colon prolapsed through rectum. Reduction is unsuccessful.

· Focal Hepatic Necrosis - Multifocal coagulative necrosis, frequently subcapsular, with minimal or no inflammation. May be a terminal event due to portal blood flow changes.

· Chronic Hepatopathy - Characterized by variably severe periportal and interstitial fibrosis, hepatocellular degeneration, bile duct proliferation suggestive or an anoxic change.

· Liver Contusion - Fracture of the capsule of the liver with hemorrhage into the peritoneum. Caused by trauma, mishandling, falls.

· Foreign Body Pneumonitis - Pneumoconiosis - focal pulmonary lesions associated with inhalation of food or bedding materials. Incidental finding with animals on wood chips or rice straw. At necropsy there may be areas of atelectasis, or circumscribed nodules in the parenchyma of the lung, usually not visible grossly. Recent lesions will have plant fiber lodged in small airways with PMN’s and macrophages, lesions of longer duration will exhibit focal granulomatous bronchiolitis and alveolitis with macrophages and multinucleated giant cells. Plant fibers are birefringent, an incidental finding that may complicate research.

· Freund’s Adjuvant Granuloma - After subcutaneous injection of Freund’s, multifocal granulomatous response in lung.

· Cataracts - Autosomal dominant, possibly associated with IDDM or L-tryptophan deficiency. Will get lens desiccation with long-term anesthesia.

· Pea Eye - Hyperplastic nodule of lacrimal or zygomatic gland origin on inferior conjunctival sac.

· Fatty Infiltration of the Pancreas - The proportion of exocrine pancreas decreases with age with no apparent impairment of function. Histologically, there are large areas of adipose tissue between normal pancreatic tissue.

· Thymus - Degenerating thymocytes are frequently observed in close association with Hassell’s corpuscles, especially in younger animals. They may evolve into thymic cysts.

· Germfree Animals - Germfree animals have a disproportionately large cecum. In conventional animals the cecum comprises about 10% of the body weight; whereas, in germfree it comprises about 25-30%. Predisposes animals to rupture, herniation, torsion, volvulus and uterine prolapse; Germfree animals also have hypoplastic lymph nodes and lymphatics along the gastrointestinal tract, lower WBC’s, changes in WBC differentials, and serum protein concentration.

· Hairless - Euthymic strain available, useful in dermal research. Hair follicles form and produce rudimentary hair. Hair present on face and feet. Non pigmented. Fragile.

· Malocclusion of Teeth - Open rooted maxillary premolar and molar teeth overgrow laterally to the labial mucosa. Mandibular premolar and molar teeth overgrow to the lingual side and occasionally incarcerate the tongue. Will see weight loss, anorexia, salivation, wasting. May see secondary malocclusion of the incisors. Cause varied; may be improper diet, a genetic predisposition (e.g., high incidence in strain 13 involving more than one gene with incomplete penetrance), one report of flurosis (caused impairment of dentin and enamel formation). Guinea pig teeth grow continuously throughout life, at necropsy food particles will be trapped around cheek teeth. Cheek teeth will have irregular contours and sharp edges.

· Neuritis- Sciatic inflammation and muscle necrosis due topoorly placed IM injection of ketamine. May see swelling and lameness, or on more severe cases self mulilation of foot and leg. Microscopic will see muscle necrosis, regeneration and degeneration, sub acute to chronic perineural inflammation, perivascular inflammation.

· Heat Stress- excessive salivation, rapid shallow breathing, hyperemia of extremities, elevated body temperature. Tissues congested, and serosal surfaces tacky at necropsy.

· Fracture- Animals not familiar with grids may fracture legs after stepping into holes.