Male, Coimbra's titi (Callicebus coimbrai)This monkey was kept at the zoological park in Belo Horizonte, Brazil. It was found on the floor in a cage, prostrated and hypothermic. It received emergency therapy with fluids, corticosteroids, glucose, and heating, but died soon after the initial treatment.

Gross Description:  

Grossly, the mesenteric lymph nodes were hemorrhagic, the colon was dilated with multifocal and moderate hemorrhage in the serosa. The colon content was hemorrhagic with a few blood clots, and large amounts of fibrinous exudate. There was sand in the oral cavity, esophagus, and stomach. The heart was mildly dilated. On the surface and cut surfaces of the liver, there was a prominent lobular pattern. Kidneys and adrenal glands were moderately congested.

Histopathologic Description:

Multifocal to coalescing and severe necrosis associated to multifocal and moderate hemorrhage was observed in the mucosa of the colon. Myriads of round, 30-50 m diameter, eosinophilic staining trophozoites were diffusely distributed in the lumen, necrotic mucosa, crypts, and lamina propria of the colon. There was a multifocal and mild infl-ammatory infiltrate composed of ly-mphocytes, histiocytes and neutrophils in mucosa and submucosa. Some epithelial cells of the colonic crypts had numerous circular, intensely basophilic cytoplasmic structures, which were interpreted as apoptotic bodies.

Morphologic Diagnosis:  

Large intestine, colon: Colitis, necrotizing, hemorrhagic, acute, multifocal to co-alescing, severe with numerous protozoal organisms consistent with Entamoeba histolytica.

Lab Results:  



Entamoeba histolytica, titi monkey

Contributor Comment:  

Entamoeba histolytica is a protozoan parasite capable of invading the intestinal mucosa. It affects other organs, mainly the liver, causing amebiasis.7 Entamoeba dispar is mor-phologically similar. It also colonizes the human gut, however it has no invasive potential.1 Both species are found of non-human primates, such as monkeys, orangutans, and baboons.5

Most asymptomatic infections found worldwide are now at-tributed to Entamoeba dispar, because it is non-invasive. E. dispar is distinct but closely related to E. histolytica. This non-invasive species has im-plications for understanding the epidemiology of amebiasis.3

In humans, amebiasis is more common in developing countries. Bad conditions such as overcrowding, poor education, co-ntaminated water, and poor sanitation favor fecal-oral transmission of amoebas. This disease results in 70 thousand deaths annually. Amebiasis is considered the fourth cause of death due to protozoa.11A recent study revealed a high prevalence of E. histolytica in long-tailed macaques in the Philippines.8 Captive monkeys infected with E. histolytica is a concern not only for the animal health risk, but also due to the zoonotic nature of the disease.4

The trophozoite, which is the motile form of E. histolytica, lives in lumen of crypts in large intestine, where it multiplies and differentiates into cyst (resistant form responsible for transmission). Cysts are excreted in stools, and may be ingested by a new host through contaminated food or water. Upon ingestion of infective cysts, parasites are released in terminal ileum, with each emerging quadrinucleate trophozoite giving rise to eight uninucleated trophozoites. Trophozoites may invade the colonic mucosa and cause dysentery.3

There are some molecules produced by E. histolytica that are related to lysis of the colonic mucosa: adhesins, amoebapores, and proteases. The parasite attachment to colonic mucus blanket is due to a multifunctional adherent lectin, preventing elimination in intestinal stream. Lectins are involved in signaling cytolysis and in blocking the deposition of the injurious membrane attack complex of complement. It maybe also participates in anchorage of the ameba to proteoglycans, during invasion process.3 Peptides of E. histolytica named am-oebapores destroy phagocytosed bacteria from the microbiota that serve as the main nutrient source for the parasite. Whether amoebapores play a role in the cytolytic event has not yet been proven. Proteases produced by the parasite can degrade the extracellular matrix during invasion and contribute in the lysis of target cells.3

JPC Diagnosis:  

Colon: Colitis, necrotizing, acute, multifocally extensive, marked with crypt abscesses, goblet cell loss and numerous amoebic trophozoites.

Conference Comment:  

E. histolytica colonizes the large intestine resulting in colitis and diarrhea, and in some cases, may result in liver abscesses. E. histolytica has two morphogenetic forms: the trophozoite and infectious cyst form. Ingestion of viable cysts initiates infection and subsequent steps are discussed above. The initial attachment to mucosal enterocytes by trophozoites, mediated through adhesins and lectins, appears to be important in the initial pathogenesis and apparently plays a role in cytotoxic activity.6 The host inflammatory response contributes to tissue damage and may help facilitate infection. Important cytokines involved in the host response include IL-8, IL-6 and IL-1?; genes involved in cell proliferation also participate in the response to infection.  E. histolytica destroys host tissue and commonly causes enterocyte apoptosis; trophozoites may ingest host cells following their death. The mechanisms leading to host cell apoptosis are not completely understood, but may involve production of reactive oxygen species and oxidative stress. Other mechanisms which may be involved in cell death include amoebic trogocytosis, where the parasite ingests fragments of host cell, resulting in increases in intracellular calcium and cell death. 2 Other parasite factors which are involved in the pathogenesis include production of prostaglandin E2, which increases sodium ion permeability through tight junctions, as well as secretion of cysteine proteases which digest matrix components such as gelatin, collagen type I and fibronectin. Epithelial barrier disruption also plays an important role in infection.2 E. histolytica trophozoites normally remain in the colonic lumen. However, in some cases, the trophozoites invade the mucosa as well as mural blood vessels and lymphatics, and eventually infect the liver. Ulcerative gastritis secondary to E. histolytica infection has also been described in primates that have a sacculated stomach, which is adapted for leaf eating and fermentation. Similarly, E. histolytica-associated gastritis may also occur in macropods (kangaroos and wallabies), which likewise have a sacculated stomach. 9 Trophozoites are observed in the mucosa and gastric glands, but may also invade to the level of the submucosa, including vessels and lymphatics. E. histolytica may also cause necrotizing and ulcerative colitis in dogs and cats (likely acquired from a human source) although less commonly than in primates. In cats, E. histolytica infection has been associated with severe necrosis of the colon and cecum.9,10 It is apparently uncommon for infected dogs to shed infectious cysts. 


1. Diamond LS, Clark CG. A redescription of Entamoeba histolytica Schaudinn, 1903 (emended Walker, 1911) separating it from Entamoeba dispar Brumpt, 1925. J Eukaryot Microbiol. 1993; 40: 340–344.

2. Di Genova BM, Tonelli RR. Infection strategies of intestinal parasite pathogens and host cell responses. Front Microbiol. 2016; 7:256. doi: 10.3389/fmicb.

3. Espinosa-Cantellano M, Martínez-Palomo A. Pathogenesis of Intestinal Amebiasis: From molecules to disease. Clin Microbiol Rev. 2000; 13(2):318. 

4. Feng M, Cai J, Min X, Yongfeng F, Xu Q, Tachibana H, Cheng X. Prevalence and genetic diversity of Entamoeba species infecting macaques in southwest China. Parasitol Res. 2013; 112:1529–1536. 

5. Feng M, Yang B, Yang L, Fu YF, Zhuang YJ, Liang LG, Xu Q, Cheng XJ, Tachibana H. High prevalence of Entamoeba-infections in captive long-tailed macaques in China. Parasitol Res. 2011; 109:1093–1097.

6. García MA, Gutiérrez-Kobeh L, López Vancell R. Entamoeba histolytica: Adhesins and Lectins in the trophozoite surface. Molecules. 2015; 20:2802-2815.

7. Martínez-Palomo A, Espinosa-Cantellano M. Amoebiasis: new understanding and new goals. Parasitol Today. 1997; 14:1–3.

8. Rivera WL, Yason JA, Adao DE. Entamoeba histolytica and E. dispar infections in captive macaques (Macaca fascicularis) in the Philippines. Primates. 2010; 51:69–74.

9. Stedman NL, Munday JS, Esbeck R, Visvesvara GS. Gastric amebiasis due to Entamoeba histolytica in a Dama Wallaby (Macropus eugenii). Vet Pathol. 2003;40:340-342. 

10. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. 6th ed. Vol 2. St. Louis, MO: Elsevier; 2016:98-99.

11. World Health Organization. 1998. The World Health Report 1998. Life in the 21st century: a vision for all. World Health Organization: Geneva, Switzerland.

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2-1 . Colon, titi monkey.

2-2. Colon, titi monkey.

2-3. Colon, titi monkey.

2-4. Colon, titi monkey.

2-5. Colon, titi monkey. 

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