Signalment:  

10 year-old intact female rhesus monkey (Macaca mulatta), nonhuman primate.The animal belonged to a breeding group of rhesus monkeys housed in an indoor-outdoor facility with free access to a large outdoor enclosure. This monkey was found dead without prior signs of illness.

Gross Description:  

Gross pathologic findings were limited to the abdominal cavity. Severe hepatomegaly was demonstrable, with fibrous transformation of the liver tissue affecting nearly all lobes and the gallbladder. Multiple cysts of different sizes were distributed throughout the fibrous hepatic tissue. The cysts had a diameter up to 5 cm that were filled with gelatinous to liquid material and contained hydatid sand. A generalized subacute peritonitis was a concomitant finding. The mesenteric lymph nodes appeared enlarged. Similar multiloculated cysts were present in the pancreas.

Histopathologic Description:

Histopathologic examination revealed metacestodal tissue in all liver samples. The liver parenchyma was destroyed by infiltrative growing cysts of different sizes which were surrounded by a fibrous hyaline membrane. Most cysts appeared empty. Single cysts contained protoscolices, arrays of hooklets and brood capsules. Calcareous corpuscles were present in the vicinity of the germinal layer. The cysts were surrounded by chronic inflammatory cell infiltration with foreign body-type giant cells.

Morphologic Diagnosis:  

Liver: hepatitis, granulomatous, chronic, multifocal, severe, with metacestodes consistent with Echinococcus multilocularis, rhesus monkey (Macaca mulatta), non-human primate.

Lab Results:  

Immunohistochemistry: Echinococcus multilocularis: positive

Condition:  

Echinococcus multilocularis

Contributor Comment:  

Echinococcus belongs to the phylum of Platyhelminthes, the class of Cestodea and subclass of Eucestodia. The genus of Echinococcus is subordinated to the order of Cyclophyllidea and the family of Taeniidae. Echinococcosis is a zoonotic disease, caused by adult or larval stages of cestodes which belong to the genus Echinococcus. Up to now, four species of Echinococcus are known E. granulosus, E. multilocularis, E. oligarthrus and E. vogeli. The life of the parasites shows a cyclic structure.

The alveolar echinococcosis (AE) is an infectious disease which is caused by the second larval stage (metacestode) of the fox tapeworm. The adult parasite lives in the gastrointestinal tract of foxes of the genera Vulpes and Alopex, which are the definitive hosts. The eggs, including the first larval stage (oncosphere), get outside with the feces and are ingested by intermediate hosts, which typically are rodents of the family Arvicolidae. In the intermediate host, the oncosphere penetrates the intestinal wall and enters the blood system. Via the blood stream, the oncosphere reaches different organs, especially the liver. Once the oncosphere has reached the liver it starts to develop into the metacestode stage. In contrast to E. granulosus with the development of a unilocular cyst, the typical cyst of E. multilocularis shows a multilocular structure. The cyst with brood capsules and protoscolices may disturb the functions of the liver, depending on its size and location. The development of protoscolices can take several months. There may be several thousand protoscolices within a cyst. If protoscolices are ingested by a definitive host, they develop to the sexually mature adult tapeworm, approximately four to six weeks after infection. Thus, the cycle is closed(5).

All mammals (including man and nonhuman primates) in which metacestodes develop may be an intermediate host, but it is important to distinguish between a real intermediate host, which plays a role in the perpetuation of the cycle, and an accidental intermediate host like this monkey, which is a dead end for the parasite.

Many monkey species are susceptible to infection with E. multilocularis(1,2,6,7). In recently described small outbreaks, only a few species were affected (five M. fascicularis and two Gorilla gorilla(7) or 12 M. fuscata(8)). A larger outbreak at the German Primate Center affected three different Old World monkey species simultaneously in a period of 12 years(9). In this largest reported outbreak, cynomolgus monkeys are the species at risk. As previously reported, the percentage of infected cynomolgus monkeys among colonies of captive primates was conspicuously high (> 50%)(3).

Since the 1990s, E. multilocularis infection is spreading geographically and increasing infection rates of red foxes have been noted in Eastern and Western European countries(4). In Northern Germany, Denmark and Poland, prevalence rates in foxes are usually < 5%, but focal areas of higher prevalence exist. Animals in zoological gardens and in institutional colonies in the northern hemisphere are at risk and alveolar echinococcosis must be considered as an emerging disease. Certain species of non-human primates are very susceptible to alveolar echinococcosis and may thus indicate previously unknown areas of high transmission.

JPC Diagnosis:  

1. Liver: Hydatid cyst, multiloculated, with hepatocellular loss and fibrosis, and mild granulomatous hepatitis.
2. Liver: Amyloidosis, diffuse, moderate. 

Conference Comment:  

Amyloid, confirmed by Congo red staining, diffusely expands the space of Disse throughout the liver adjacent to the hydatid cysts. Secondary amyloidosis is frequently the major complication of several chronic inflammatory diseases. The incidence of AA amyloidosis is relatively high in cases with granulomatous diseases of known etiology such as tuberculosis, leprosy and osteomyelitis. Metazoan parasiteinduced amyloidosis has also been reported in rodent filariasis, human schistosomiasis, and rodent and non-human primate alveolar hydatidosis. Hydatid cysts trigger a massive influx of leukocytes at the focus of infection.(1) Elaboration of cytokines in chronic inflammation stimulates increased positive acute phase proteins, such as serum amyloid A (SAA). Regulation of synthesis of acute phase proteins is largely modulated by cytokines such as IL-6, IL-1, TNF-alpha, IFN-gamma, and TGF-beta, and has been shown to influence the serum concentration of acute phase proteins. SAA is the most sensitive acute phase protein, and serum levels of SAA have been used both in diagnosis and monitoring of inflammatory and infectious diseases. Amyloidosis is thought to be due to either the defective degradation of SAA or the production of abnormal SAA that is resistant to degradation(10).

References:

1. Bacciarini LN, Gottstein B, Pagan O, Rehmann P, Gr+�-�ne A. Hepatic alveolar echinococcosis in cynomolgus monkeys (Macaca fascicularis). Vet Pathol 41:229-234, 2004
2. Brack M, Tackmann K, Conraths FJ, Rensing S. Alveolar hydatidosis (Echinococcus multilocularis) in a captive rhesus monkey (Macaca mulatta) in Germany. Trop Med Int Health 2(8):754-759, 1997
3. Deplazes P, Eckert J. Veterinary aspects of alveolar echinococcosis-a zoonosis of public health significance. Vet Parasitol 98(1-3):65-87, 2001
4. Eckert J, Conraths FJ, Tackmann K. Echinococcosis: an emerging or re-emerging zoonosis? Echinococcosis: an emerging or re-emerging zoonosis? Int J Parasitol 30(12-13):1283-1294, 2000
5. Meyers WM, Neafie, RC, Marty AM, Wear DJ. Hydatidosis. In: Pathology of Infectious diseases, Vol. I Helminthiasis, pp. 145-164. Armed Forces Institute of Pathology, 2000
6. Rehmann P, Grone A, Lawrenz A, Pagan O, Gottstein B, Bacciarini LN. Echinococcus multilocularis in two lowland gorillas (Gorilla g. gorilla). J Comp Pathol 129:85-88, 2003
7. Rehmann P, Grone A, Gottstein B, Sager H, Muller N, Vollm J, Bacciarini LN.: Alveolar echinococcosis in the zoological garden Basle. Schweiz Arch Tierheilkd 147(11):498-502, 2005
8. Sato C, Kawase S, Yano S, Nagano H, Fujimoto S, Kobayashi N, Miyahara K, Yamada K, Sato M, Kobayashi Y. Outbreak of larval Echinococcus multilocularis infection in Japanese monkey (Macaca fuscata) in a zoo, Hokkaido: western blotting patterns in the infected monkeys. J Vet Med Sci 67:133-135, 2005
9. Tappe D, Brehm K, Frosch M, Blankenburg A, Schrod A, Kaup F-J, M+�-�tz-Rensing K. Echinococcus multilocularis infection of several Old World monkey species in a breeding enclosure. Am J Trop Med Hyg.77(3):504-506, 2007
10. Zachary JF. Mechanisms of microbial infections. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier; 2012:287-8.

Click the slide to view.

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02-1. Liver, rhesus macaque.

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