E. histolytica is the most common organism causing pathogenic amoebiasis globally. It was only relatively recently that not one, but three forms of Entamoeba were identified—pathogenic E. histolytica and nonpathogenic E. dispar and E. moshkovski. E. histolytica—although relatively uncommon in the USA, is a common cause of diarrhea in some developing countries, particularly India, Africa, Mexico, and Central and South America. This organism is an uncommon cause of traveler’s diarrhea. It is believed that prevalence is higher among homosexual males, and there have been outbreaks in this population attributed to sexual transmission [9]. Unfortunately, accurate prevalence data likely does not exist because of the recent discovery of nonpathogenic strains that were previously classified as E. histolytica and the large proportion of persons who are asymptomatic carriers [10].

Similar to Giardia, Entamoeba exists in two life forms. There is a more stable cyst form that is responsible for transmission of infection between hosts and a more virulent trophozoite form that is responsible for causing clinical symptoms [5, 11, 12]. Generally, cysts are excreted into soil and are then consumed in contaminated food or water, or via sexual contact. They remain stable in the environment for weeks and are highly virulent—consuming one cyst is adequate to infect a new host. Once consumed, they undergo excystation in the small bowel. The binding and penetration of the trophozoite into the colonic wall result in an invasive colitis. Once the organism has penetrated the colonic mucosa, it is capable of damaging colonic epithelial cells and inflammatory cells through multiple mechanisms [13]. See Figs. 16.1 and 16.2.

The clinical manifestations of E. histolytica are variable. Toxic megacolon, colonic ulcerations leading to perforation or formation of an ameboma—granuloma of the cecum or ascending colon caused by chronic amebic infection—are among the more serious intestinal complications. Fulminant amebic dysentery can ensue and be fatal. However, many patients who test positive for E. histolytica will only have mild diarrhea or be asymptomatic. Liver abscess and other extraintestinal manifestations of E. histolytica are generally seen without recent or concurrent intestinal symptoms [5].

Testing for E. histolytica infection can be achieved with multiple different methods. Conventional stool microscopy, stool antigen testing, and serology with enzyme immunoassay are useful in different clinical settings. Stool microscopy requires laboratory expertise and three separate stool collections on three separate days, making it more tedious. Additionally, microscopy will not differentiate among the three strains of Entamoeba and will only be diagnostic when active intestinal disease is present. Thus, patients suspected of having E. histolytica liver abscess should have serologic testing performed. Stool antigen testing is not universally available, but is efficient and both sensitive and specific for intestinal E. histolytica. Polymerase chain reaction (PCR) is the test of choice to differentiate among strains of Entamoeba. Direct biopsy of the colonic mucosa can be used as a last resort [12].

Treatment is advised in asymptomatic carriers as well as patients with symptomatic disease [13]. Symptomatic patients with suspected invasive disease should be treated initially with systemic therapy for extraluminal disease and then with a luminal therapy for complete clearance. Nitroimidazoles (metronidazole and tinidazole) are commonly used and well tolerated for initial therapy in the setting of invasive disease (invasive colitis, liver abscess). Asymptomatic carriers, and those with invasive disease who have completed initial therapy, should be treated with a luminal agent, most commonly paromomycin or iodoquinol, to prevent both spread to others and development of new or recurrent invasive disease (Table 16.1) [5, 13]. It is important to note that those with peritonitis secondary to colonic perforation will require broad-spectrum antibiotics as well as the two-phase therapy noted above.

Dientamoeba was long considered a commensal organism in the gut, but is now considered pathogenic and should be treated in the absence of other causes for GI symptoms. It has a global distribution and many studies indicate that the global prevalence could be higher than Giardia [14]. The age and gender distribution of patients with Dientamoeba has also been a source of disagreement among various studies [14]. It is clear, however, that this pathogen is most common among populations with other parasitic infections who live in conditions with poor hygiene.

D. fragilis is a binucleate, single-cell organism that is of the trichomonad family but lacks flagella. Transmission is presumed to be fecal-oral, but there is no cyst form of Dientamoeba, so it is less stable in the environment. Because it has been associated with high carriage rates of Enterobius vermicularis (pinworm), some believe helminthic infection may be a vector of transmission [5, 15].

The illness typically causes gas, bloating, abdominal pain, and diarrhea. Diagnosis has improved significantly with the advent of stool PCR testing (sensitivity 96 %), increasing the recognition of this pathogen [15]. Dientamoeba has also been associated with chronic bowel symptoms, such as IBS, and thus, if found in patients who have chronic symptoms of unclear etiology, treatment is suggested [14]. Providers should consider testing for pinworm infection in patients who test positive for D. fragilis. Interestingly, despite the lack of invasiveness of this organism, it is associated with eosinophilia, perhaps because of concurrent pinworm infection. Treatment is with a nitroimidazole (i.e., metronidazole) and several regimens have been studied and found effective (Table 16.1).

Blastocystis species (previously referred to as B. hominis) are similar to D. fragilis in that their role as pathogens is still emerging. They have a global distribution and can affect both children and adults. Zoonotic transmission and fecal–oral routes of infection have been implicated. Thus, it is not surprising that higher rates of infection have been observed in developing countries where infection rates from 30 to 50 % have been observed, compared to only 5–10 % in developed countries. Immunocompromised hosts (HIV, transplant recipients) are also more commonly affected [16].

Blastocystis species are anaerobic organisms that have been observed to have four major life forms and significant genetic diversity, which led to their renaming from B. hominis to B. species. Once they have been ingested, they live in the cecum and colon of their hosts. While asymptomatic infection can occur, symptoms can include diarrhea, flatulence, bloating, abdominal pain, nausea, and anorexia. Additionally, there is some association with urticarial disease [16]. Diagnosis is challenging and most frequently made with stool microscopy; however, enzyme-linked immunosorbent assay (ELISA) and PCR tests are likely superior. Treatment requires some clinician judgment because infections can be self-limited or asymptomatic and may not require therapy. Metronidazole and trimethoprim–sulfamethoxazole (TMP-SMX) are two commonly prescribed medications that are effective for treating Blastocystis species [5, 16].