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UNIVERSITY OF CALIFORNIA, DAVIS
BERKELEY  DAVIS  IRVINE  LOS ANGELES  RIVERSIDE  SAN DIEGO  SAN FRANCISCO SANTA BARBARA  SANTA CRUZ
CALIFORNIA NATIONAL PRIMATE RESEARCH CENTER
DAVIS, CALIFORNIA 95616-8542
(530) 752-0447
CASE 3 – Slide # MCY26400-1
CONTRIBUTORS: Valverde CR, Tarara RP*, Spinner A, Roberts JA
INSTITUTION: California National Primate Research Center, University of California–
Davis, Davis – CA 95616-8542
SIGNALMENT: 5-year-old female Cynomolgus monkey (Macaca fascicularis) from the
Philippines
HISTORY:
On quarantine screen a moderate anemia was detected (hemoglobin 9.8 g/dl), 1+
Balantidium coli and Strongyle ova. Abdominal ultrasonography showed that there were diffuse,
heterogeneous echogenic changes of the hepatic parenchyma.
GROSS FINDINGS:
Three samples of light brown tissue were presented in formalin; two were cylindrical
measuring 4 mm. long and 1mm. in diameter and one was spherical measuring 1,5 mm. in
diameter.
HISTOPATHOLOGIC FINDINGS:
Multifocally there is zonal expansion of portals areas due to increased fibrous connective
tissue and a moderate pleocellular inflammatory cell infiltrate consisting of eosinophils,
lymphocytes, histiocytes, plasma cells, and multinucleated giant cells. Admixed with the
inflammatory cells there are round to oval structures measuring 75 to 100 µm long by 50 to 75 µm
in diameter delimited by an amber thin wall 3 to 5 µm thick. Some of the structures are empty and
others contain eosinophilic and punctate basophilic material. Some of these oval structures are
disrupted, fragmented and surrounded by multinucleated giant cells. Other changes consist of a
mild increase in bile duct elements, moderate diffuse vacuolation of hepatocyte cytoplasm, and a
small amount of coarsely granular brown-pigmented material within hepatocytes.
MORPHOLOGIC/ETIOLOGIC DIAGNOSIS:
Hepatitis, granulomatous, periportal, moderate with intra-lesional parasite ova (probable
Schistosoma spp.)
DISCUSSION:
This report characterizes a naturally occurring infection of Schistosoma
japonicum in a cynomolgus macaques. Schistosomiasis affects 200 million people worldwide and
is effectively treated by antiparasitic medication; however there is interest in continuing to
develop an antischistosomiasis vaccine. Chronic inflammation and hepatic fibrosis contributes
significantly to debility and death due to schistosome infection.
Hepatic sonographic changes in this case prompted a diagnostic work-up, which included
a fecal examination (sedimentation concentration and direct smear) and liver biopsy. Hepatic
tissue changes with accompanying intra-lesional ova consistent with schistosome infection were
seen and ova were identified on direct fecal smear.
A mammalian host is infected by contact with freshwater containing the infectious cercariae
which penetrate intact skin and develop into a schistosomule in the subcutis. Intense irritation at
this site can cause “swimmer’s itch”. After a period of development, schistosmules enter the
peripheral circulation and travel to the lung and subsequently settle in the portal venous system
where maturation into male and female occurs. The female resides within the gynecophoric
groove of the male. Fertilization occurs when spermatozoa from the male are introduced into the
female; fertilized eggs are released from the female and either penetrate the intestinal wall into the
lumen and are discharged in the feces or become trapped in tissues, often the intestinal submucosa
or the liver where they elicit a chronic inflammatory reaction. The T-helper response in the early
stages of inflammation is dominated by Th 1 cells and the later stages of inflammation are
dominated by Th 2 cells which are required for the ova-induced granulomatous response.
Miracidium larvae hatch from ova discharged in the feces and infect snails where they complete
the life cycle by developing into infective cercariae.
In human beings schistosomiasis can cause severe anatomical changes, but may be
accompanied only by mild clinical manifestations. For this reason, asymptomatic schistosomiasis
should be considered when evaluating imported nonhuman primates from endemic areas of the
disease and hepatic sonographic screening is an effective diagnostic tool.
REFERENCES:
Cheng TC 1964. The Biology of Animal Parasites, WB Saunders, Philadelphia
Grzych JM et al. 1991. Egg Deposistion is the Major Stimulus for the Production of Th2
cytokines in murine Schistosomiasis Mansoni. The Journal of Immunology, 16(4): 1322-1327.
Kaplan MH et al. 1998 Th2 Cells Are Required For the Schistosoma mansoni Egg-Induced
Granulomatous Response. The Journal of Immunology, 160: 1850-1856.
King CH et al. 2006 Transmission Control for Schistosomiasis-Why It Matters. Trends in
Pararsitology, 22 (12): 575-582.
McAdam AJ and Sharpe AH 2005 Robbins and Cotran Pathologic Basis of Disease,7th edition,
Elsevier Saunders, Philadelphia
Meneghin A and Hogaboam CM 2007 Infectious Disease, The Innate Immune Response and
Fibrosis. The Journal of Clinical Investigation, 17(3): 530-538.
Rumbley, CA et al. 1998 The Schistosome Granuloma: Characterization of Lymphatic Migration,
Activation, and Cytokine Production. The Journal of Immunology, 4129-4137.
Stavitsky, AB 2004 Regulation of granulomatous Inflammation In Experimental Models of
Schistosomiasis. Infection and Immuntiy 72(1):1-12.