Occurrence of multinucleated hepatocytes in cynomolgus monkeys (Macaca fascicularis) from different geographical regions.

Multinucleated hepatocytes (MNHs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. However, information is sparse on variations in incidence in the cynomolgus macaque (Macaca fascicularis). A survey was conducted to assess the occurrence of MNHs in the liver of stock (nonstudy) animals from SNBL SRC (Alice, TX) and SNBL USA (Everett, WA) submitted for diagnostic purposes. A total of 215 cynomolgus monkeys originally from Cambodia (61), China (5), Indonesia (125), and Mauritius (24) were used for this investigation. From each animal, usually 2 liver samples were processed for histopathology with 2 sections in each slide. An MNH was defined as a hepatocyte with 3 or more nuclei. A threshold of 3 MNHs was selected for the Multinucleated Hepatocyte Grading System: 0 = not remarkable (≤3 MNHs counted from 2-4 liver sections), minimal = 4 to 15 MNHs, mild = 16 to 30 MNHs, moderate = 31 to 59 MNHs, and severe ≥60 MNHs. The incidence of MNHs was 60 of 86 (70%) in males and 72 of 129 (56%) in females for a total overall incidence of 132 of 215 animals (61%). Affected hepatocytes were frequently observed close to the capsule and generally had 3 to 8 nuclei per hepatocyte but as many as 15 occurred in a single cell. Awareness of the incidence of MNHs in cynomolgus monkeys is important for potential use as background data in preclinical safety and toxicity evaluation studies.

Spinosad insecticide: subchronic and chronic toxicity and lack of carcinogenicity in CD-1 mice.

The potential toxicologic and oncogenic effects of spinosad, a natural fermentation product with insecticidal properties, were investigated. The 13-week toxicity study consisted of groups of 10 CD-1 mice/sex provided diets containing 0, 0.005, 0.015, 0.045, or 0.12% spinosad (Study 1). The 0.12% group was terminated on Test Day 44 due to mortality and overt clinical signs of toxicity. An 18-month chronic oncogenicity study consisted of groups of 50 CD-1 mice/sex provided diets containing 0, 0.0025, 0.008, or 0.036% spinosad (Study 2). Two interim groups of 10 mice/sex/group were terminated after 3 and 12 months. Females given 0.036% were terminated on Day 455 due to markedly lower body weights and feed consumption, as well as excessive mortality. Because of the early termination of the female high-dose group, additional groups of 10 male and female mice (12-month interim necrospy) and 50 male and female mice (18-month necropsy) were provided diets containing 0, 0.0008, or 0.024% spinosad (Study 3) to fully assess potential chronic toxicity and oncogenicity. Standard toxicologic parameters were evaluated consistent with existing regulatory guidelines. The primary effect in the 13-week and 18-month studies was intracellular vacuolation of histiocytic and epithelial cells in numerous tissues and organs at doses of > or = 0.015%. The histological vacuolation corresponded to ultrastructural lysosomal lamellar inclusion bodies. This alteration was consistent with phospholipidosis, a condition that results from accumulation of polar lipids in lysosomes. Lesions with no apparent direct relation to vacuolation were hyperplasia of the glandular mucosa of the stomach, skeletal muscle myopathy, bone marrow necrosis, and anemia with associated splenic hematopoiesis. The incidence of tumors in mice given spinosad was not increased relative to controls at any dose level. The no observed effect level for the 13-week study was 0.005% (6 mg/kg/day) spinosad, and for the chronic toxicity/oncogenicity study was 0.008% (11 mg/kg/day) spinosad for male and female CD-1 mice.

Spinosad insecticide: subchronic and chronic toxicity and lack of carcinogenicity in Fischer 344 rats.

Spinosad is an insecticide derived from a naturally occurring bacterium via fermentation. The toxicity of spinosad was characterized in subchronic and chronic toxicity/oncogenicity studies conducted according to standard toxicology regulatory guidelines. Subchronic toxicity was evaluated in groups of 10 Fischer 344 rats/sex given feed containing 0, 0.05, 0.1, 0.2, or 0.4% spinosad (Study 1) or 0, 0.003, 0.006, 0.012, or 0.06% spinosad (Study 2) for 13 weeks. Lower body weights and increased mortality occurred in rats given 0.4% spinosad. Microscopic effects were observed in the adrenal glands, liver, lymphoid cells, reproductive tissues, kidney, thyroid, stomach, lung, and skeletal muscle of rats given > or = 0.05% spinosad, and consisted primarily of vacuolation of cells; however, degenerative, regenerative, and/or inflammatory changes were also noted in some tissues. Vacuolation within a number of tissues was ultrastructurally characterized by an increase in size and number of lysosomes that contained extensive membranous whorls consistent with phospholipidosis. The no observed effect level (NOEL) in the 13-week studies was 0.012% (24 mg/kg/day) spinosad. Chronic toxicity and oncogenicity were evaluated in groups of 60 Fischer 344 rats/sex given feed containing 0, 0.005, 0.02, 0.05, or 0.1% spinosad for up to 2 years. Rats given 0.1% spinosad for 1 year had microscopic effects similar to those observed in the subchronic studies. Vacuolation and inflammation of the thyroid gland also occurred in rats given 0.05% spinosad for 1 year. Excessive mortality occurred in rats from the oncogenicity study given 0.1% spinosad by 21 months, and surviving rats were euthanized because the maximum tolerated dose had been exceeded. Rats given 0.05% spinosad for 2 years had vacuolation and/or inflammation involving the thyroid, lymphoid tissue, and lung. Rats given 0.05% spinosad had similar numbers of neoplasms as control rats, indicating that spinosad was not carcinogenic at dose levels up to 0.05%. The NOEL at 2 years was 0.005% (2.4 mg/kg/day) spinosad.

Turkey knockdown in successive flocks.

Turkey knockdown was diagnosed in three of five flocks of hen turkeys on a single farm within a 12-mo period. The age of birds in the flocks affected ranged from 6 wk 2 days to 7 wk 4 days. The attack rate ranged from 0.02% to 0.30% with a case fatality rate in affected birds ranging from 0 to 74%. The diagnosis was made on the basis of clinical signs and histopathologic lesions associated with knockdown. The feed in all flocks contained bacitracin methylene disalicylate and monensin (Coban). Affected birds were recumbent, demonstrated paresis, and were unable to vocalize. Postmortem examination revealed few significant lesions although pallor of the adductor muscles and petechiation in adductor and gastrocnemius muscles were noted. Birds that had been recumbent for extended periods were severely dehydrated. Consistent microscopic lesions included degeneration, necrosis, and regeneration of adductor, gastrocnemius, and abdominal muscles. No lesion in cardiac tissue was noted. Results of our investigation indicated that changes in water consumption, vitamin E status, and brooder to finisher movement correlated with the occurrence of knockdown. Turkey knockdown was defined in 1993 as any condition identified in a turkey flock that has affected the neuromuscular system to a degree that a turkey is unable to walk or stand. This definition was later modified to...neuromuscular or skeletal systems to a degree that a turkey is unable to walk or stand properly. Knockdown may be associated with numerous feed, management, or disease factors alone or in combination. Dosage of monensin, feed restriction/gorging, water restriction, heat stress, copper, mycotoxins, sodium chloride in feed, and sulfa drugs have all been suggested as contributing factors; however, laboratory studies to duplicate this have not been successful. This report presents observations from a single farm at which three of five hen flocks in a single year experienced knockdown. When a flock was reported as affected, a detailed investigation was initiated within 3 hr. The fifth flock was followed on a twice weekly basis from 0 to 8 wk of age to determine if initiating events were evident, but knockdown did not occur.

Alterations in levels of various host antioxidant factors in turkey knockdown syndrome.

Five components (selenium, glutathione peroxidase, copper, superoxide dismutase, and vitamin E) of the antioxidant system of turkey poults were examined to determine if they play any role in the knockdown (KD) syndrome. All flocks were provided with feed formulated to contain monensin at 54-60 g/ton. Flock data were analyzed as a case-control study with three treatment groups (KD-affected and unaffected turkey poults from a KD flock and poults from an unaffected flock [control]). Affected turkey poults had lower (P < 0.001) serum vitamin E levels compared with unaffected poults from KD flocks or poults from unaffected flocks. No significant differences were observed for the other parameters evaluated but there was a trend towards lower copper and superoxide dismutase values in affected birds. It appears that serum vitamin E concentrations in turkey poults may play a significant role in susceptibility to or protection against KD syndrome. Other components of the antioxidant system may also be involved, and complex interactions among several body systems may be critical.

A sudden death syndrome induced in poults and chicks fed diets containing Fusarium fujikuroi with known concentrations of moniliformin.

A sudden death syndrome was induced in chicks and poults fed diets containing Fusarium fujikuroi, formulated to contain 0-330 mg/kg moniliformin (M) with or without the maximum recommended therapeutic concentration of monensin. Lesions of monensin toxicosis were not observed. Clinical signs were referable to cardiac dysfunction (sudden death, dyspnea, cyanosis, depression). Poults and chicks dying early in the study had no gross lesions or had lesions of right ventricular dilation. Treated poults and chicks dying late in the study or euthanatized at termination of the study had lesions of bilateral myocardial hypertrophy, usually concentric. Absolute heart weights and relative heart weights, expressed as a percentage of body weight, were significantly greater in treated birds than controls (P < 0.05), whereas body weights were significantly less (P < 0.05). Microscopically, lesions progressed from acute myocardial degeneration to necrosis, fibrosis, and hypertrophy. Ultrastructural findings were consistent with the gross and microscopic lesions. Serum pyruvate concentrations were a useful indicator of M-induced cardiotoxicosis. Concentrations of serum pyruvate increased with increased concentration of dietary M, but were not affected by addition of monensin to the diet. In chicks ingesting 40-300 mg/kg M, serum pyruvate concentrations were significantly greater (P > 0.05) than those in controls (controls, 0.28 +/- 0.08 mmol/liter; exposed 0.38 +/- 0.11-0.55 +/- 0.13 mmol/liter). Poults ingesting 80-330 mg/kg M had significantly greater serum pyruvate concentrations than controls (controls 0.33 +/- 0.09 mmol/liter; exposed 0.43 +/- 0.13-1.00 +/- 0.006 mmol/liter). The Vetronics System was used to evaluate electrocardiographic alterations in a limited number of chicks and poults surviving to the end of the feeding trial. Electrocardiographic alterations in poults and chicks fed diets containing > or = 40 mg/kg and > or = 160 mg/kg M, respectively, were consistent with ventricular hypertrophy, myocardial injury, and hypoxia. Electrocardiographic alterations were more striking in poults than in chicks. Altered myocardial metabolism due to M toxicosis, in conjunction with the unusual susceptibility of domestic poultry to altered cardiac metabolism, is believed to be the cause of the organ-specific lesions in these birds. These findings suggest that cardiac injury with subsequent alterations in cardiac electrical conductance may be a cause of the sudden deaths observed in poultry chronically intoxicated with dietary M.

In vitro and in vivo ultrastructural changes induced by macrolide antibiotic LY281389.

High doses of LY281389 (9-N-(n-propyl)-erythromycylamine) cause cytoplasmic vacuolar changes in striated and smooth muscle characteristic of drug-induced phospholipidosis. This study characterized phospholipidosis in striated and smooth muscle of rats and dogs, compared in vivo observations with those in a cultured rat myoblast model, and attempted to confirm the lysosomal origin of the drug-induced vacuoles. Standard transmission electron microscopy and acid phosphatase cytochemistry techniques were used to evaluate ultrastructural changes in vivo and in vitro. Rats and dogs exposed to LY281389 had a time- and dose-related increase in number and size of vacuoles containing concentric lamellar figures in cardiac and skeletal muscle. Cytochemical staining of dog stomach smooth muscle for acid phosphatase, a lysosomal enzyme, stained the periphery of vacuoles that contained concentric lamellar figures. Cultured rat L6 myoblast cells were exposed to 0.25 mg LY281389/ml for 2.5, 5, 10, 20, 30, or 90 min and 2, 6, 12, 24, or 48 hr. Cell cultures exposed for 2 hr had several predominantly large, clear, membrane-bound vacuoles, and at 6 and 12 hr there were greater numbers of large vacuoles that contained increased amounts of membranous figures. Following 24- or 48-hr exposures, vacuoles occupied most of the cytoplasmic volume, and were engorged predominantly with amorphous or granular material. These findings indicate that LY281389 can induce similar phospholipidosis-like vacuolar changes in rat and dog muscle and in a cultured rat muscle cell line. Further, positive acid phosphatase staining of drug-induced vacuolar structures, in conjunction with standard transmission electron microscopy techniques, strongly suggests that vacuoles seen in vitro and in vivo are lysosomal in origin.

Purified moniliformin does not affect the force or rate of contraction of isolated guinea pig atria.

Chronic exposure to moniliformin results in the development of myocardial hypertrophy and degeneration. The cause of this hypertrophy is unknown. However, moniliformin-induced hypoxia or altered function of cardiac pyruvate dehydrogenase, rather than direct cardiostimulation have been proposed as potential mechanisms. Isolated guinea pig atria were used in a cumulative concentration-response model to evaluate the direct effect of moniliformin on the rate and force of atrial contraction. Moniliformin did not affect the rate or force of atrial contraction. These results are consistent with the hypothesis that moniliformin does not have a cardiostimulatory effect. Therefore cardiac stimulation. e.g. stimulation of beta-adrenergic receptors, is unlikely to be the cause of the myocardial hypertrophy observed in poultry chronically intoxicated with moniliformin.

The comparative toxicology of narasin in laboratory animals.

The toxicology of narasin has been extensively investigated in several species of laboratory animals. Acute median lethal po doses varied considerably between species (> 10 to 40.8 mg/kg). Animals of various species given acutely toxic doses of narasin manifested similar clinical signs of toxicity, including anorexia, hypoactivity, leg weakness, ataxia, depression and diarrhea. Clinical effects were usually delayed 1 to several days, depending on the dose, and some were reversible even with continued narasin administration. In repeated dose toxicity studies, narasin dosages have been demonstrated at which animals could be exposed daily for long periods of time without producing harmful effects. The no-observed effect levels (NOELs) by the dietary route were 60 ppm in mice and 15 ppm in rats after 3 mo of dosing and 15 ppm in rats after 1 y. In dogs, NOELs were 1 mg/kg body weight after 3 mo and 0.5 mg/kg body weight after 1 y of dosing. In breeding animals, narasin did not affect reproductive performance through 4 generations and was not teratogenic. Two-y chronic bioassays in 2 rodent species showed that narasin did not produce cumulative toxicity or carcinogenicity. In genetic toxicity tests narasin was not mutagenic to bacterial or mammalian cells and did not induce DNA repair or sister chromatid exchange. Narasin neither caused dermal toxicity nor skin sensitization, but was a severe eye irritant in rabbits. In dogs, local irritation and systemic toxicity occurred following repeated inhalation exposure to narasin aerosol concentrations greater than 0.114 mg/M3 of air.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional encephalomalacia in turkeys: diagnosis and growth performance.

An outbreak of neurological disease in 2 1/2-to-3 1/2-week-old male turkey poults was diagnosed morphologically as nutritional encephalomalacia. About 20 to 30% of the flock of 6360 showed clinical signs, which included going down with legs extended or hock-sitting and inability to get up, incoordination, weakness, staggering, trembling, torticollis, and opisthotonus. The most important gross postmortem changes were found in the brain, which consisted of an enlarged and swollen cerebellum with focal and/or diffuse hemorrhages. Major histopathological alterations included congestion, hemorrhages, necrosis, and malacia associated with hyaline capillary thrombi affecting the cerebellar cortex and adjacent white matter. Except for a slightly higher mortality, flock performance compared favorably with performance of other flocks grown in the same farm as well as with the national average for market tom turkeys.

Feed gorging and extended water restriction do not produce knockdown in male turkeys fed monensin.

A study was conducted to determine the effects of feed restriction with subsequent gorging during extended water restriction on 27- to 57-d-old toms fed excess monensin. Four treatments were factorially arranged with two levels of dietary monensin (0 and 140 ppm) and two feeding-watering regimens (ad libitum and restricted). Ad libitum birds had full access to feed and water but restricted birds only had access to feed from 0800 to 1200 h daily. A 24-h water restriction regimen was imposed biweekly from 28 to 42 d and a 36-h water restriction regimen was imposed biweekly from 43 to 57 d. The restricted feeding and watering regimen decreased (P < .01) feed intake, weight gain, and feed efficiency. Excess monensin had no effect (P > .10) on feed intake regardless of feeding and watering regimen. Monensin had no effect on the weight gain and feed efficiency of ad libitum birds, but monensin exacerbated the decrease on gain (monensin by regimen, P < .01) and feed efficiency (monensin by regimen, P < .09) induced by feed and water restriction. No treatment-related abnormalities were observed during either interim or terminal necropsies. Neither clinical signs of ionophore toxicity nor pathologic findings attributed to monensin treatment were observed during the study. Based on these observations, feed gorging and water restriction will not adversely affect the health status of, or increase the mortality rate of, 4- to 8-wk-old male turkeys fed monensin.

Inoculation of conventionally and specific-pathogen-free reared rabbits with Ostertagia ostertagi isolated from cattle.

Eleven trials were conducted to collect helminthologic and pathologic data from 27 conventionally reared (CR) and 53 specific-pathogen-free (SPF) 6- to 13-week-old male New Zealand White rabbits. These rabbits were given 50,000 to 100,000 ensheathed third-stage infective Ostertagia ostertagi larvae (L3) orally. The L3 had been isolated from the feces of cattle. Fecal egg counts were conducted and worm populations were determined after euthanasia 3 to 56 days after inoculation. At necropsy, nodules were observed in a confluent pattern in the mucosa of cardiac region of the stomach in all inoculated rabbits, except in CR rabbits inoculated at 6 weeks of age, which had no nodules or worm burdens 42 days after inoculation. Confluent areas were not observed in SPF rabbits euthanatized 5 days or less after inoculation; however, small, transparent nodules were evident in the mucosa of the cardiac region of the stomach. Fourth-stage larvae (L4) were obtained from the mucosal nodules after digestion of stomach of both types of rabbits. There were more L4 in SPF than CR rabbits. In addition, greater numbers of L4 were found in SPF rabbits euthanatized 14 days or less after inoculation. Petechial hemorrhages were in the fundic area of the stomach mucosa in SPF rabbits inoculated with 100,000 L3 and euthanatized 14 days later. Mature O ostertagi or worm eggs in feces were not found in inoculated CR or SPF rabbits. The pathologic changes had characteristics similar to those in cattle and goats infected with O ostertagi.(ABSTRACT TRUNCATED AT 250 WORDS)

The veterinary importance of the toxic syndrome induced by ionophores.

Monensin, lasalocid, salinomycin, narasin and maduramicin are carboxylic ionophores intended for use as anticoccidial drugs for poultry and as growth promotants for ruminants. Generally, ionophores have been found safe and effective in the target animals receiving recommended dosage levels. However, toxic syndromes can result from overdosage and misuse situations. More information and reports of adverse reactions are available for monensin than the other ionophores because of monensin's longstanding and widespread use in the poultry and livestock industries. Care must be exercised in the diagnosis of ionophore toxicoses since clinical signs and lesions are not pathognomic. However, a feed-related problem characterized clinically by anorexia, diarrhea, dyspnea, ataxia, depression, recumbency and death, and pathologically by focal degenerative cardiomyopathy, skeletal muscle necrosis, and congestive heart failure may warrant a presumptive diagnosis of ionophore toxicity. Confirmatory diagnosis will require considerations of differential diagnoses and laboratory assays to determine the specific ionophore involved. Presently, there is no antidote or treatment for toxicoses induced by the ionophores. Judicious use, avoidance of overdosing, and adherence to species recommendation will help prevent the occurrence of adverse effects associated with this class of compounds.

An immunosuppressed rat model of respiratory cryptosporidiosis.

A rat model is described in which animals develop respiratory cryptosporidiosis, a disease which is well documented in immunocompromised patients, especially those with AIDS. Our present lack of knowledge of the pathophysiology and immunology of Cryptosporidium parvum respiratory infections warrants the development of a laboratory animal model. Lewis rats immunosuppressed by subcutaneous injection of methylprednisolone acetate and inoculated intratracheally with 10(6) C. parvum oocysts developed a reproducible infection consisting of all known developmental stages in the epithelium lining airways from the trachea to the terminal bronchioles. Developmental stages were morphologically indistinguishable from those seen in gut epithelium. Infections were apparent at 4 days post-inoculation, and at 10-14 days post-inoculation, rats exhibited respiratory distress and severe weight loss and had enlarged, elastic lungs. Increased mucus production and exfoliative necrosis of the epithelium resulted in accumulation of large amounts of mucocellular exudate throughout the airways and patchy alveolitis involving alveoli emerging from respiratory bronchioles.

A retrospective survey of endocardial proliferative lesions in rats.

Sixty, proliferative, endocardial lesions were diagnosed in 19,304 rats, for an overall incidence of 0.3%. This population consisted of 10,127 Fischer 344, 8,737 Wistar, 200 Sprague-Dawley, and 240 Long Evans rats from chronic/oncogenicity studies reported at Lilly Research Laboratories from 1976 to 1988. Of the 60 proliferative lesions, 44 were classified as endocardial hyperplasia, 15 as endocardial schwannomas, and one as an endocardial sarcoma for prevalence rates of 0.2%, 0.08%, and 0.005%, respectively. Affected rats ranged in age from 42 to 110 weeks. There were no sex or treatment-related differences in the prevalence of the rat endocardial proliferative lesions. A review of endocardial lesions in 18 of 233 Wistar rats treated with carbamate derivatives revealed endocardial hyperplasia in 12 rats, schwannomas in five rats, and a sarcoma in one rat. One of the 12 rats with endocardial hyperplasia also had an intramural schwannoma. Of 200 Wistar rats given N-nitroso-N-methylurea, two had endocardial hyperplasia, and one had an endocardial schwannoma. Morphologic features were similar in either spontaneous or treatment-associated hyperplasia or neoplasia of the rat endocardium. Probable Schwann cell origin of the endocardial proliferative lesions was indicated by positive immunohistochemical staining for S-100 antigen in 10/12 spontaneous and 11/14 carcinogen-associated endocardial hyperplastic lesions. Further, 15/16 spontaneous and 6/7 carcinogen-associated neoplasms were immunoreactive to S-100. No tumor metastasis was recorded in either the spontaneously affected or carcinogen-treated rats.

Pulmonary lesions in disseminated visceral coccidiosis of sandhill and whooping cranes.

Fifty cranes, consisting of 46 sandhill (Grus canadensis) and four whooping cranes (Grus americana), were studied. Eighteen sandhill cranes and the four whooping cranes were naturally infected with disseminated visceral coccidiosis (DVC). The remaining sandhill cranes were chicks experimentally infected with oocysts of Eimeria reichenowi and/or E. gruis; five chicks served as controls. There were no clinical signs attributed to respiratory infection. Necropsy of naturally infected adult birds revealed nodules in many organs, including the lung, air sacs, trachea and nares. Artificially infected sandhill cranes and the whooping crane chicks that died from DVC had congestion and consolidated areas in the lung with frothy fluid in the airways. Grossly visible nodules were observed from 10 days postinoculation. Granulomatous pneumonia and tracheitis were observed with light microscopy. Lesions were associated with merogonic and gametogonic stages of eimerian coccidia. Granulomas and granulomatous foci contained parasitized large mononuclear cells. Merogonic stages were seen in lymphoid cells by ultrastructural examination. Oocysts were observed in the trachea and bronchial mucosa and admixed with exudate in the airways, indicating that crane eimerians can complete their life cycle at these sites. Of the few eimeriid coccidia that have extraintestinal stages of development in birds and mammals, only the species in cranes complete their life cycle in both the digestive and respiratory tracts.

A redescription of the life cycle of Eimeria mitis Tyzzer, 1929.

Ten-day-old broiler chickens were inoculated with oocysts of a characterized strain of Eimeria mitis, and tissues were fixed at 4, 8, or 24-h intervals after inoculation for histopathological examination. Tissue collections were initiated at the time of inoculation and extended up to 168 h postinoculation. The preferred site of development of E. mitis was found to be the ileum although more limited development of the parasite also took in the jejunum, cecal pouches, cloaca, and bursa of Fabricius. No distinctive and consistent intestinal lesions were macroscopically evident even in heavily parasitized chickens. The prepatent period was approximately 92 h postinoculation. The histopathological features of the E. mitis infections were characterized using conventional bright-field microscopy as well as both scanning and transmission electron microscopy. No extra-intestinal development of the parasite was observed.

Disseminated visceral coccidiosis in sandhill cranes.

Disseminated visceral coccidiosis (DVC) caused by Eimeria spp was first recognized as a disease entity in captive sandhill cranes (Grus canadensis) and whooping cranes (G americana) at the Patuxent Wildlife Research Center. Because cranes produced at the Center are reintroduced to the wild to augment wild populations, studies involving both experimentally induced and natural infections were initiated to determine the potential or actual occurrence of DVC in wild Gruidae. Nine sandhill cranes dosed orally with eimerian oocysts of wild origin developed lesions characteristic of DVC. Extraintestinal granulomas associated with developing schizonts were found in 6 birds. Similar lesions were observed in wild sandhill cranes throughout parts of midwestern United States, Alaska, and Saskatchewan. These studies revealed the wide geographic distribution and the high frequency of occurrence of DVC in wild cranes.

Clinical and pathologic features of experimental Schistosoma japonicum infection in pigs.

Nine piglets, 2-5 months old and weighing 12-15 kg were infected percutaneously with 5000 to 6000 cercariae of Schistosoma japonicum. Three similar piglets which were not infected served as controls. Infected animals were necropsied at 5, 10, 30, 40, 59, 90, 120, 150 and 180 days post-infection (PI) and the controls at 5, 60 and 180 days PI. The prepatent period varied from 27 to 33 days after infection. Clinical signs observed, coincident with egg production, were loss of appetite, lethargy, pallor of mucous membranes, diarrhea, progressive emaciation and dehydration. One piglet was moribund when killed for necropsy at 40 days and another piglet died 59 days PI. Pathological changes induced by S. japonicum included erythematous papules on the site of inoculation, petechial hemorrhages in the lungs, catarrhal to hemorrhagic enteritis, bluish-gray discoloration of the liver, and egg granulomas in the liver, lungs, spleen, intestines, pancreas and mesenteric lymph nodes. Endophlebitis with intimal hyperplasia was occasionally observed in veins harboring adult schistosomes.