Amebiasis 

Amebiasis is caused by Entamoeba histolytica, a protozoan found worldwide. The highest prevalence of amebiasis is in developing countries where barriers between human feces and food and water supplies are inadequate.

Although most cases of amebiasis are asymptomatic, dysentery and invasive extraintestinal disease can occur. Amebic liver abscess is the most common manifestation of invasive amebiasis, but other organs can also be involved, including pleuropulmonary, cardiac, cerebral, renal, genitourinary, and cutaneous sites. In developed countries, amebiasis primarily affects migrants from and travelers to endemic regions, men who have sex with men, and immunosuppressed or institutionalized individuals.

E histolytica is transmitted via ingestion of the cystic form (infective stage) of the protozoa. Viable in the environment for weeks to months, cysts can be found in fecally contaminated soil, fertilizer, or water or on the contaminated hands of food handlers. Fecal-oral transmission can also occur in the setting of anal sexual practices or direct rectal inoculation through colonic irrigation devices. Excystation then occurs in the terminal ileum or colon, resulting in trophozoites (invasive form). The trophozoites can penetrate and invade the colonic mucosal barrier, leading to tissue destruction, secretory bloody diarrhea, and colitis resembling inflammatory bowel disease. In addition, the trophozoites can spread hematogenously via the portal circulation to the liver or even to more distant organs.

Amebic infection was first described by Fedor Losch in 1875 in St. Petersburg, Russia. In 1890, Sir William Osler reported the first North American case of amebiasis, when he observed amebae in stool and abscess fluid from a physician who previously resided in Panama. The species name E histolytica was first coined by Fritz Schaudin in 1903. In 1913, in the Philippines, Walker and Sellards documented the cyst as the infective form of E histolytica. The life cycle was then established by Dobell in 1925.

E histolytica is a pseudopod-forming, nonflagellated protozoal parasite that causes proteolysis and tissue lysis (hence its name) and can induce host-cell apoptosis. Humans and perhaps nonhuman primates are the only natural hosts. Ingestion of E histolytica cysts from the environment is followed by excystation in the terminal ileum or colon to form highly motile trophozoites. Upon colonization of the colonic mucosa, the trophozoite may encyst and is then excreted in the feces or may invade the intestinal mucosal barrier and gain access to the blood stream and disseminate to the liver, lung, and other sites. Excreted cysts reach the environment to complete the cycle.

Disease may be caused by only a small number of cysts, but the processes of encystation and excystation are poorly understood. The adherence of trophozoites to colonic epithelial cells seems to be mediated by a galactose/N -acetylgalactosamine (GAL/GalNAc)–specific lectin.^{[1, 2, 3]} A mucosal immunoglobulin A (IgA) response against this lectin can result in fewer recurrent infections.^[4] Both lytic and apoptotic pathways have been described. Cytolysis can be undertaken by amoebapores, a family of peptides capable of forming pores in lipid bilayers.^[1] Furthermore, in animal models of liver abscess, trophozoites induced apoptosis via a non-Fas and non–tumor necrosis factor-α1 receptor pathway.^[5] The amoebapores, at sublytic concentrations, can also induce apoptosis.

Cysteine proteinases have been directly implicated in invasion and inflammation of the gut and may amplify interleukin (IL)–1–mediated inflammation by mimicking the action of human IL-1–converting enzyme, cleaving IL-1 precursor to its active form.^{[1, 6]} The cysteine proteinases can also cleave and inactivate the anaphylatoxins C3a and C5a, as well as IgA and immunoglobulin G (IgG).^{[7, 8]}

Epithelial cells also produce various inflammatory mediators, including IL-1B, IL-8, and cyclooxygenase-2, leading to the attraction of neutrophils and macrophages.^{[9, 10]} Corticosteroid therapy is known to worsen the clinical outcome, possibly because of its blunting effect on this innate immune response. Additional host defenses, including the complement system, could be inhibited directly by the trophozoites, suggested by the finding that a region of the GAL/GalNAc–specific lectin showed antigenic crossreactivity with CD59, a membrane inhibitor of the C5b-9 attack complex in human red blood cells.^[11] Trophozoites that reach the liver create unique abscesses with well-circumscribed regions of dead hepatocytes surrounded by few inflammatory cells and trophozoites and unaffected hepatocytes, suggesting that E histolytica are able to kill hepatocytes without direct contact.^[1]

The genus Entamoeba contains many species, some of which (ie, E histolytica, Entamoeba dispar, Entamoeba moshkovskii, Entamoeba polecki, Entamoeba coli, Entamoeba hartmanni) can reside in the human interstitial lumen. E histolytica is, thus far, the only Entamoeba species definitely associated with disease; the others are considered nonpathogenic.^[12] More recent studies have recovered E dispar and E moshkovskii from patients with gastrointestinal symptoms, but a causal relationship is undetermined.^[12]

E dispar and E histolytica cannot be differentiated by direct examination, but recent molecular techniques established them as two different species, with E dispar being commensal (including in patients with HIV infection) and E histolytica pathogenic.^[12] In fact, it is now estimated that many individuals with Entamoeba infections are colonized with E dispar, which appears to be 10 times more common than E histolytica.^[12] However, in certain regions (eg, Brazil, Egypt), asymptomatic E dispar and E histolytica infections are equally prevalent.^[1] In Western countries, approximately 20%-30% of men who have sex with men are colonized with E dispar.^[12]

Frequency

United States

The overall prevalence of amebiasis is approximately 4%. However, certain groups are predisposed to amebic colitis, including very young patients, pregnant women, recipients of corticosteroids, and malnourished individuals.^[1] In 1993, a total of 2970 cases of amebiasis were reported to the Centers for Disease Control and Prevention (CDC); 33% of cases were reported in Hispanic immigrants and 17% in immigrants from Asia or the Pacific Islands. Travelers to endemic areas are at risk for infection; 10% of individuals returning with diarrhea were found to have amebiasis.^[1] Amebic liver abscess has been reported in travel exposures as short as 4 days (median, 3 mo), whereas amebic colitis is uncommon in short-term travelers.

The US national death certificate data from 1990 to 2007 identified 134 deaths from amebiasis. A declining trend of deaths was noted and over 40% occurred in residents of California and Texas with US-born persons accounting for the majority of amebiasis deaths.^[18]

International

Entamoeba species infect approximately 10% of the world's population. The prevalence of Entamoeba infection is as high as 50% in areas of Central and South America, Africa, and Asia.^[14] In Egypt, 38% of individuals presenting with acute diarrhea to an outpatient clinic were found to have amebic colitis.^[1] E histolytica seroprevalence studies in Mexico revealed that more than 8% of the population were positive.^[15] Asymptomatic E histolytica infections seem to be region-dependent, as high as 11% in Brazil. Since the introduction of molecular techniques, it is estimated that 500 million individuals with Entamoeba infection are colonized by E dispar.^[12]

Mortality/Morbidity

• Amebiasis is second only to malaria in terms of protozoa-associated mortality. The combined prevalence of amebic colitis and amebic liver abscess is estimated at 40-50 million cases annually worldwide, resulting in 40,000-100,000 deaths.^{[12, 1, 16]}
• Asymptomatic intestinal amebiasis occurs in 90% of infected individuals. However, only 4%-10% of individuals with asymptomatic amebiasis who were monitored for one year eventually developed colitis or extraintestinal disease.^[12]
• Case fatality rates associated with amebic colitis range from 1.9%-9.1%. Amebic colitis evolves to fulminant necrotizing colitis or rupture in approximately 0.5% of cases; in such cases, the mortality rate jumps to greater than 40%.^[17]
• The mortality rate due to amebic liver abscess has fallen to 1-3% in the last century following the introduction of effective medical treatment. Nevertheless, amebic liver abscess is complicated by sudden intraperitoneal rupture in 2-7% of patients, leading to a higher mortality rate.^[1]
• A study of 134 deaths in the United States from 1990-2007 found that mortality rates were highest in men, Hispanics, Asian/Pacific Islanders, and people at least 75 years of age. Although deaths declined during the course of the study, 40% occurred in California and Texas.^[18]

Race

• In Japan and Taiwan, HIV seropositivity is a risk factor for invasive extraintestinal amebiasis.^[19] This has not been observed elsewhere.

Sex

• Amebic colitis affects both sexes equally.^[1]
• Amebic liver abscess is 7-12 times more common in men than in women, with a predominance among men aged 18-50 years. The reason for this sexual disparity is unknown, although hormonal effects may be implicated, as the prevalence of amebic liver abscess is also increased among postmenopausal women. Alcohol may also been an important risk factor. The sexual distribution is equal in children.^[1]

Age

Very young children seem to be predisposed to fulminant colitis.