Recent molecular and immunological techniques have demonstrated two distinct species of
Entamoeba that are morphologically identical. E. histolytica is pathogenic, causing symptomatic disease in 10% of infections whereas E. dispar causes only asymptomatic colonization. In addition to the E. histolytica strain, other risk factors for invasive disease are interaction with bacterial flora, host genetic susceptibility, malnutrition, male sex, young age and immunodeficiency. Entamoeba coli and E. hartmanni are also non-pathogenic morphologically distinct members of the genus.
The E. histolytica life cycle consists of an infective cyst (10-15 |im in diameter) and an invasive trophozoite (10-60|im in diameter). Cysts are resistant to chlorination, gastric acidity and desiccation and can survive in a moist environment for several weeks. For transmission of E. histolytica, cysts are ingested from fecally contaminated food and water and encystation occurs in the intestine, transforming the cyst into eight trophozoites. Mucosal invasion by trophozoites leads to colonic ulcers with migration of parasites to the liver via the portal vein.
It is estimated that 500 million people are infected with E. histolytica in the world with 50 million per year developing invasive disease and 50 000100 000 deaths. The case/fatality rate is 1 per 500-1000 diagnosed cases, but in a hospital setting, the case/fatality ratio in children is higher, with 9% mortality and 27% morbidity. Liver abscess and extra-abdominal amebiasis has a much higher mortality rate of 10-40% or up to 90% for cerebral amebiasis.
The epidemiology of amebiasis has been complicated by the difficulty of identifying two genetically identical but morphologically distinct species, E. histolytica and E. dispar. It is estimated that 10% of the population is colonized by Entamoeba but 90% of these are with non-pathogenic E. dispar. Although E. dispar distribution is worldwide, E. histolytica infection occurs predominantly in Central and South America, Africa and the Indian subcontinent. Prevalence studies based on stool parasites measure predominantly E. dispar, whereas serological surveys reflect the incidence of E. histolytica, since E. dispar does not cause seroconversion.
A Bangladeshi study of urban children found the prevalence of E. histolytica to be 4.2% compared to 6.5% for E. dispar with the highest prevalence of E. histolytica infection in children with diarrhea aged 6-14 years.132 A Mexican national survey reported an 8.4% seropositivity to E. histolytica, peaking at 11% in the 5-9-year-old age group, with 4.2% of diarrheal cases due to E. histolytica infection, and 6.5% with E. dispar.132 Children 6-14 years of age with diarrhea had the highest incidence of E. histolytica infection (8%), whereas rural asymptomatic children had a 1% prevalence of E. histolytica and 7% prevalence of E. dispar. Shigella (dysenteriae and flexnerii) were also more frequent in children with diarrhea who also had Entamoeba infection. A West African study in school children found a ratio of E. histolytica : E.dispar of 1 : 46 (compared to 1 : 3-9 in Asian studies), suggesting that the vast majority of Entamoeba infections in this region are not pathogenic.133 A Brazilian study documented a 10.6% colonization rate for E. histolytica (excluding E. dispar), affecting predominantly those of poor socioeconomic status, hygiene and nutritional status, but most infections were asymptomatic and self-limited (clearing within 30-45 days) and reinfection rates were low.134
Amebic disease occurs when trophozoites invade colonic tissue, which is initiated by prior adherence to mucins lining the surface of the large bowel followed by enzymatic destruction of the basement membrane and underlying tissue. The resulting inflammatory response contributes further to tissue destruction. The stages of amebic infection include: adherence to bacteria (especially Escherichia coli) and intestinal epithelial cells via galactose-binding lectin, which protects the parasite by blocking complement; activation of virulence factors in parasites such as cysteine proteinases; stimulation of intestinal epithelial cells to produce cytokines and inflammatory mediators by activation of NF-kB; the resulting release of chemokines leading to neutrophil influx; medi ators greatly contributing to the destruction of host tissues by lytic necrosis and apoptosis, enabling amebic invasion.135
Cell-mediated immunity limits the extent of invasive amebiasis and protects the host from recurrence, including trophozoite killing by activated macrophages and cytotoxic lymphocytes. Cytokines such as TNF-a and interferon-/ contribute to immunocompetent cell activation. Innate resistance to infection in children is linked to the absence of serum anti-trophozoite IgG, which is inherited, whereas acquired resistance is linked to intestinal IgA and serum antibodies to a parasite lectin.136,137
The initial colonic lesion in amebiasis is a small intraglandular ulcer of only 1 mm, which extends only to the muscularis mucosa. Margins may be hyperemic with slight edema of the surrounding mucosa. The next stage involves deeper buttonhole ulcers which are up to 1 cm in diameter and extend into the sub-mucosa. In young children this can progress to a fulminant necrotizing colitis associated with transmural necrosis. Amebomas are uncommon in children but involve the formation of granulation tissue with a fibrous outer wall, which may result in stricture or obstruction to the lumen. Dissemination to the liver occurs in a high proportion of patients with fulminant disease.
The carrier state is the most common form of amebic infestation with all E. dispar infections and up to 90% of E. histolytica infections remaining asymptomatic with only cysts in the feces. Amebic dysentery is the most common form of symptomatic disease, with gradual onset of symptoms over 3 or 4 weeks after infection with increasingly severe diarrhea with abdominal pain such that an acute abdomen is often suspected. Stools contain blood and mucus, fever occurs in about half, and a small proportion develop abdominal distension with dehydration. Occasionally, young children present in a more fulminant manner with intussusception, perforation, peritonitis or necrotizing colitis. Rarely, children with amebic dysentery may present with an abdominal mass that has an 'apple-core' appearance on radiographs, similar to colonic carcinoma. Amebic liver abscess and extra-abdominal amebiasis are much less common in children than in adults.
The diagnosis of amebiasis should be considered in any child with blood or mucus in the stools, particularly if associated with abdominal pain or distension. Stool microscopy will yield cysts in < 30% of infected individuals, owing to the intermittent nature of cyst shedding, although multiple examinations increase the diagnostic yield to 60-70% with amebic colitis but to under half of amebic hepatic abscesses.
Serology can be helpful with invasive amebiasis since asymptomatic infections with E. dispar do not usually elicit a serological response. The gold standard remains culture or iso-enzyme analysis, but stool antigen detection tests are now commercially available which are more reliable than microscopy. A PCR-based amplification technique is now available for stool samples; infecting isolates are genetically diverse, with differences between those associated with intestinal and hepatic disease.138 The major problem with sero-logical tests is that they remain positive for years after an episode of amebiasis, so they may not be useful in endemic areas.
Wet preparations of material aspirated or scraped from the base of ulcers on colonoscopy can be examined for motile trophozoites and tested for E. histolytica antigen. The appearance of amebic colitis resembles inflammatory bowel disease with a granular, friable and diffusely ulcerated mucosa. It is preferable for biopsy specimens to be taken from the edge of ulcers, but the sensitivity of this method of diagnosis appears variable.
Prevention requires interruption of the fecal-oral spread of the infectious cyst stage of the parasite by improved hygiene, sanitation and water treatment. This is of course very difficult in the developing world. Current efforts towards a vaccine are focusing on the adherence lectin, which may prevent colonization. This would lead to elimination of the parasites if effective, since humans are the only significant reservoir of E. histolytica infection.
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