Amebiasis

Definition

Amebiasis is due to infection with the enteric protozoan parasite Entamoeba histolytica . Amebiasis can cause asymptomatic colonization, diarrhea, dysentery, and colitis. It also can spread extraintestinally to cause liver and rarely brain abscess ( Fig. 323-1 ).

Epidemiology

Most E. histolytica infections occur in the developing world, including the Indian subcontinent, Southeast Asia, sub-Saharan Africa, and Central and South America, as a result of fecal-oral transmission. A national serologic survey in Mexico demonstrated antibody to E. histolytica in 8.4% of the population. In an urban slum of Fortaleza, Brazil, 25% of the population carried antibody to E. histolytica , and the prevalence in children 6 to 14 years of age was 40%. In Dhaka, Bangladesh, where diarrheal diseases are the leading cause of childhood death, the annual incidences of amebic infection, diarrhea, and dysentery are about 45%, 9%, and 3%, respectively. The annual incidences of amebic liver abscess was 21 cases per 100,000 inhabitants in Hue City, Vietnam. The best current estimate by the World Health Organization is that E. histolytica infection results in nearly 50 million symptomatic cases each year worldwide and as many as 100,000 deaths annually.

In the United States, amebiasis is the third most common parasitic infection after giardiasis and cryptosporidiosis (1.2 cases/100,000 U.S. population). Most cases in industrialized countries occur in travelers to and immigrants from endemic regions as well as in institutionalized individuals. In returning travelers ( Chapter 265 ), diarrhea is the predominant reason for a patient to visit a physician, and amebiasis is the second most common cause of diarrhea in returning travelers. Previously reported high rates of E. histolytica infection in men who have sex with men in the United States actually reflect a high prevalence of Entamoeba dispar infection in this population. In contrast, in Asia, amebiasis is more frequently an initial symptom of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome because of the common risk for acquisition of both HIV infection and amebiasis through the sexual practices of men who have sex with men. The typical patient with an amebic liver abscess in the United States is a 20- to 40-year-old Hispanic male immigrant. Several groups are at increased risk for severe amebiasis, including the very young or old, malnourished persons, pregnant women, and patients treated with corticosteroids.

Pathobiology

Killing of host cells is required for invasion of the intestine by the parasite. The process of host cell destruction includes sequential steps of adherence, a nibbling-like process termed amebic trogocytosis, contact-dependent cytotoxicity, and finally phagocytosis of the host cell corpse. The initial contact of parasite to host is mediated by the parasite’s galactose and N -acetyl- d -galactosamine (Gal/GalNAc)–specific lectin, which binds to carbohydrate determinants on the host’s intestinal epithelium. Human cells die by apoptosis induced by E. histolytica , a process that requires attachment of the Gal/GalNAc lectin to a host cell’s receptor, as well as the parasite’s acid intracellular vesicles, which may serve as delivery vehicles for an amebic pore-forming protein. E. histolytica initiates apoptosis in host cells by directly activating the host cell’s distal apoptotic machinery; caspase 3 is activated within minutes of E. histolytica adherence, a caspase 3 inhibitor blocks E. histolytica killing, and caspase 3–deficient or bcl-2–overexpressing mice are resistant to amebic infection. Recognition and ingestion of the apoptotic host cell’s corpse are required for colonic infection by the parasite, and multiple ligands and receptors are involved, including the Gal/GalNAc lectin, a phosphatidylserine receptor, serine-rich E. histolytica protein, and collectins. After ingestion of the corpse of the host cell, additional parasitic factors participate in invasion into the intestinal mucosa. For example, E. histolytica encodes at least 44 cysteine proteinase genes that have been implicated in degradation of colonic mucin glycoproteins; digestion of extracellular matrix, hemoglobin, and villin; and inactivation of interleukin-18 (IL-18).

The innate immune response to amebic infection is coordinated by lymphoid cells type 2, which produce a protective type 2 immune response in response to amebic infection. In the murine model of intestinal amebiasis, innate resistance is conferred by nonhematopoietic cells, thus suggesting the importance of epithelial production of cytokines such as tumor necrosis factor-α (TNF-α), IL-1α, IL-6, IL-8, growth-related oncogene-α (GRO-α), and granulocyte-macrophage colony-stimulating factor. Granulocytes are the earliest innate cellular immune response (within 1 to 2 days) for both intestinal and hepatic amebiasis. Depletion of neutrophils or eosinophils in a murine model results in exacerbated amebic hepatic and intestinal disease. Macrophages and T lymphocytes are also recruited by day 3 of an infection. Macrophages acquire amebicidal activity after in vitro stimulation with interferon-γ (IFN-γ), TNF-α, or colony-stimulating factor 1.

The acquired immune response reflects the opposing roles of IL-4 and IFN-γ in persistence and clearance of amebic infection, respectively. Inbred mice of the CBA strain are susceptible to intestinal amebiasis and develop a rapid T _H 2 phenotypic immune response, and this response is deleterious insofar as inhibition of IL-4 can convert the response to a healing IFN-γ response. The IL-33-ILC2 pathway also appears to be an important host defense mechanism. Effective acquired immunity in humans is associated with both a systemic IFN-γ and a mucosal immunoglobulin (Ig)A response directed at the Gal/GalNAc lectin. Children with mucosal IgA against the Gal/GalNAc lectin have 86% fewer new E. histolytica infections in the following year. Similarly, the risk for amebiasis is 50% lower in children who are in the 50th percentile and above for the production of IFN-γ by peripheral blood mononuclear cells stimulated with soluble amebic antigen. Children with an amino acid polymorphism in the receptor for leptin are protected from symptomatic infection with amebiasis, thereby reflecting the importance of leptin for gut mucosal innate immunity. The composition of the gut microbiome also is associated with symptomatic amebiasis, likely by induction of an inflammatory immune response.

Clinical Manifestations