Clinical manifestations diagnostics and treatment of E histolytica infection

Colitis and severe diarrhoea

In Nordic countries amoebiasis cases are of two categories, immigrants or residents of tropical and subtropical regions and travellers. Short-term travellers as opposed to long-term

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travellers and residents of endemic areas seem to have a significantly higher rate of E. histolytica to E. dispar infection (Walderich et al. 1997).

The incubation time is dependent on the infectious dose and may vary from a few days to months. Usually symptoms appear after 2-4 weeks. Acute amoebic colitis is manifested as abdominal pain, tenderness, watery diarrhoea, and frequent bloody stools. In proctoscopy, ulcerations with a 'punced out' appearance are typically associated with E. histolytica colitis. Severe disease is more commonly seen in association with malnutrition, pregnancy, immunosuppressive therapy, and in children. The enterotoxic activity of E. histolytica appears to be due to several factors, including secretagogues, like neurohormones and prostaglandins, which may originate both from the parasite and the host (see Ravdin 1988).

The diagnostics is based on finding haematophagous E. histolytica trophozoites in microscopy. However, this is a method of low sensitivity (see, e.g. Walderich et al. 1997). As pointed out in the paragraph on diagnostic methods, the finding of cysts of E. histolytica/ dispar is largely misinterpreted as diagnostic for E. histolytica infection.

Extraintestinal infection and amoebic liver abscess

Colonic perforations are commonly seen in fulminant colitis. This may lead to peritonitis which is reported to occur at a frequency of 3-5%. In highly endemic areas, such as Mexico, amoebic liver abscess has been found in 5.8% of autopsies. Amoebic liver abscess is due to haematogeneous dissemination of amoebas. Tissue destruction is caused by proteolytic enzymes in part released from host polymorphonuclear leucocytes which are lysed by amoebas. Trophozoites may be found in a minority of cases in the abscess fluid by microscopy. The parasites are located at the edge of the abscess in contact with hepatocytes (Healy 1988). The diagnosis is based on radiology and serology. Parasite nucleic acids can be demonstrated by polymerase chain reaction (PCR) (see subsequently). In most cases of invasive amoebiasis a specific humoral antibody response is seen. Several methods are in routine use in diagnostic laboratories measuring antibodies against E. histolytica. The sensitivity of diagnostic serology is in the order of 80%. False negative results are seen especially during the early phase of amoebic liver abscess formation, possibly due to excess amoebic antigen being released during the invasive process. Positive serology in a non-endemic area may be a more reliable diagnostic tool than the same assay in an endemic region.

Identification of E. histolytica/dispar

The common procedure for stool examination involves formol-ether (ethylacetate) concentration of faecal cysts and ova (Ridley and Hawgood 1956). The identification of Entamoeba species in human stool is based on the size of the trophozoite and cyst, nuclear morphology, and number of nuclei in mature cysts as well as on the morphology of the chromatoid bodies that appear during encystation. Cysts of E. histolytica are 10-16 in diameter with four. Glycogen in a vacuole and chromatoid bodies are distinct in the immature cysts, becoming more diffuse upon maturation. Morphologically E.

histolytica and E. dispar cysts are indistinguishable. This is, however, possible using novel techniques (see subsequently).

Prevalence of E. histolytica/dispar and of E. histolytica

As discussed earlier, prevalence numbers in the literature on 'E. histolytica' are based on routine stool examination, and in fact may be either E. histolytica or E. dispar. Thus, despite

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the estimated high rates of E. histolytica/dispar-infected individuals (50 million cases globally is a figure in the literature, see Ravdin 1988; the reported prevalence in Sweden is about 500 yearly cases), amoebiasis apparently occurs only in a few per cent of these individuals.

The reason for this low figure is twofold. First, the relative prevalence of E. histolytica is about 1 in 10 (Anonymous 1997). Second, even in E. histolytica-infected individuals, symptoms related to amoebiasis seem to be lacking in at least one-third of the cases. The figure may be even lower as it may be impossible to rule out other causes of enteric symptoms, such as enterotoxic Escherichia coli and enteric viruses (Walderich et al. 1997), and in fact there is data suggesting that in most cases colonization with E. histolytica is asymptomatic (Braga et al. 1996; Gilchrist and Petri 1999). The reported high number of clinically diagnosed cases of amoebic infection is a problem as it has consequences with respect to treatment and handling of both diarrhoeal patients and asymptomatic individuals. This risk of coincidental presence of E. dispar cysts in patients with diarrhoea is of course higher in situations where E. histolytica/dispar is prevalent. The reported E. histolytica/dispar prevalence seems to be around 10% in tropical and sub-tropical countries, but may be higher: E. histolytica/dispar was isolated in 345 out of 3536 individuals (9.7%) of subjects living in rural communities around Delhi but there was no increase in the prevalence rate of bowel symptoms in the culture-positive compared to the culture-negative subjects (Anand et al. 1993).

There is some variation in the reported relative proportion of E. histolytica among E. histolytica/dispar cyst carriers and so far the estimated 10% (Anonymous 1997) is based on rather limited materials. Of the 313 individuals studied 15% had E. histolytica/dispar cysts in the stools at the Seychelles and 8/40 (20%) had E. histolytica (Sargeaunt 1992). In northeastern Brazil 14 out of 155 individuals (9.0%) carried E. histolytica/dispar and 4 out of 10 stools (29%) had E. histolytica by detection of the Gal/ GalNAc lectin in stool infection (Braga et al. 1996).

The presence of E. histolytica/dispar cysts in stools apparently correlates to sexual activities that allow for oral-faecal contamination and thus not to homosexuality per se (see Ravdin 1988). Entamoeba histolytica/dispar is frequently found among male homosexuals, with a prevalence of 25-35% and in some communities over 50%. Sargeaunt et al. found that among 52 isolates of E. histolytica/dispar from 470 stools no pathogenic zymodemes were found (Sargeaunt et al. 1983) and in Recife only 1 of 77 stools had cysts of E. histolytica/dispar, and this was of non-pathogenic zymodeme (E. dispar) (de Alencar et al. 1996). The conclusion from a careful evaluation is that there are no data to suggest that finding cysts of E. histolytica/ dispar implies that E. histolytica is a pathogen in homosexual men. (Goldmeier et al. 1986). However, of 28 symptomatic amoebic patients studied retrospectively in Tokyo, almost half had positive serology for Treponema pallidum or HIV, and indicated that they engaged in homosexual practices (Ohnishi and Murata 1997).

This finding of E. histolytica/dispar cysts has been associated with intestinal symptoms, 'the gay bowel syndrome'. It is important, however, to critically evaluate the significance of finding E. histolytica/ dispar cysts in stools of patients as chronic abdominal pain and frequent bowel disturbance are common symptoms experienced by more than 15% of apparently healthy people. In areas endemic for E. histolytica infection, these symptoms are often diagnosed as 'non-dysenteric intestinal amoebiasis'. In a study addressing this problem more than 60% of cyst-positive as well as cyst-negative patients with symptoms showed either complete or partial response to treatment strategy for irritable bowel syndrome. Thus it was concluded that chronic bowel symptoms, such as pain in the abdomen and frequent bowel disturbance, have no association with either past or present infection with E. histolytica and

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that '.. .the clinical entity of non-dysenteric intestinal amoebiasis, if it exists, must be extremely rare'. Most patients with such symptoms are likely to have 'irritable bowel syndrome' (Anand et al. 1997). Serology, as discussed later, is a potent diagnostic tool for invasive amoebiasis, but serology has also been used for seroepidemiology. While only 3% of older children, in the Brazilian study refered to earlier, carried E. histolytica, 40% developed serologic evidence of having experienced pathogenic E. histolytica infection (Braga et al. 1996). Thus positive serology reflects the presence of E. histolytica in a community - which needs to be considered in the evaluation of diagnostic significance of antibodies against E. histolytica.


Two classes of anti-amoebic drugs are in use: luminal amoebicides (such as diloxanide furoate and paromycin) and tissue amoebocides (such as 5-nitroimidazoles). To treat invasive infection, tissue amoebocide treatment is followed by treatment with luminal amoebicides. If E. histolytica/dispar is found in symptomatic patients it should not be assumed that E. histolytica is the cause of the symptoms and other explanations for the symptoms should also be considered. Chemoprophylaxis is never appropriate (Anonymous 1997).

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