Prevalence of Non-Dysenteric Intestinal Amebiasis

ABSTRACT & COMMENTARY

Synopsis: Non-dysenteric intestinal amebiasis is, at most, a very rare condition.

Source: Anand AC, et al. Does non-dysenteric intestinal amoebiasis exist? Lancet 1997;349:89-92.

Abdominal discomfort and irregular bowel habits are common in the general population. In areas where Entamoeba histolytica is endemic, however, physicians and patients often blame vague abdominal symptoms on ameba. In an effort to determine how common non-dysenteric amebiasis actually is, investigators in Pune, India, evaluated 144 patients with abdominal symptoms (pain, increased stool frequency, flatulence, diarrhea) and 100 asymptomatic controls. They found no difference in the prevalence of E. histolytica in stools (18% vs 18%) or in the prevalence of positive E. histolytica serology (42% vs 41%). Colonoscopic abnormalities and histopathological abnormalities were found more often in the symptomatic group, but these differences were not significantly different on statistical analysis. Comparison of cyst-positive and cyst-negative individuals showed no difference in serologic evidence of invasive E. histolytica, histopathologic abnormalities, or response to a therapeutic trial of metronidazole. The majority of patients met criteria for a diagnosis of irritable bowel syndrome and responded well to therapy specific to that diagnosis. Thus, neither abdominal pain nor non-dysenteric bowel symptoms seemed to be associated with evidence of either current or past E. histolytica infection. Non-dysenteric intestinal amebiasis does not appear to be a significant problem in this area where amebic infection is common.

COMMENT BY PHILIP R. FISCHER, MD

A central African patient once told me about the best lab in her country. When asked what made it "the best," she responded that "they could always find something, even if no one else could." Patients and physicians often desire to find explanations for symptoms and can be quick to blame a variety of symptoms on whatever seemingly pathogenic agent is found on stool exam. Infecting more than half a billion people on our planet, Entamoeba species have been blamed for a variety of symptoms ranging from heartburn to constipation.

Individuals who regularly eat corn often find visible corn kernels in their stool, regardless of whether they have any particular symptoms. Similarly, people who repeatedly ingest food or water contaminated with Entamoeba species often find amebic cysts in their stool regardless of whether they have any symptoms. Just as corn should not be blamed for all abdominal symptoms, neither should physicians be too quick to blame abdominal symptoms on ameba which might, like corn, just be an incidental finding.

Anand’s report from India documents a careful investigation to evaluate whether amebic species might be the cause of vague abdominal discomfort or other gastrointestinal symptoms. They found no evidence that either the presence of amebic cysts in the stool or the finding of positive amebic serology was related to symptoms such as abdominal pain, flatulence, increased stool frequency, and diarrhea. Using logic similar to that of mycobacterial researcher Koch in the 1800s, they could not support the notion that non-dysenteric symptoms are associated with amebic infection.

Clearly, E. histolytica is responsible for significant pathology around the world. This protozoal parasite is reputed to cause more than 50,000,000 cases of invasive colitis or liver abscess each year; approximately 100,000 of these patients have fatal infections.1 Entamoeba is a rare cause of travelers’ diarrhea, but even short-term travelers are clearly at risk of developing amebic liver abscesses. Typically, these abscesses become symptomatic approximately three months after a return from an endemic area, and an exposure as brief as four days has been related to an amebic liver abscess in a traveler.2

For returned travelers without either dysentery or a liver abscess, is there a role for microscopic screening of stool for ameba? Medically, such screening would probably not be justified. As less than 10% of amebic cysts diagnosed morphologically as E. histolytica are pathogenic,3 most cyst-positive patients without specific symptoms are not at risk of invasive amebic disease. A test that could identify pathogenic ameba, however, might be useful so that infected returned travelers could be treated before developing dysentery or a liver abscess. Patients with non-pathogenic ameba could be spared the expense and risk of unnecessary treatment.

Of course, symptomatic patients with amebic liver abscess or dysentery or the rarer manifestations of E. histolytica infection such as cutaneous amebiasis and ameboma can benefit from proper therapy. In such cases, serologic testing that gives evidence of an antibody response to invasive (and thus pathogenic) amebic infection might be useful.

Might it be possible to specifically identify the pathogenic ameba from the multitude of individuals who harbor amebic cysts in their intestinal tracts? In 1925, the French microbiologist Emile Brumpt suggested that two species of ameba, E. histolytica and E. dispar, appeared morphologically identical but were pathogenically very different. If E. dispar, the non-pathogenic species, was much more common (as it now appears to be), the facts that most infected patients never become ill from their infection and that most cyst-passers do not spread disease to other individuals would be readily explained. For 50 years, Brumpt’s hypothesis was disregarded. Then, in the late 1970s, investigators studying isoenzyme patterns (zymodymes) in ameba suggested that there were indeed two morphologically identical species among the protozoa previously categorized as E. histolytica. Since that time, growing genetic, immunologic, and biochemical data further support the distinction between the two different yet morphologically indistinguishable Entamoeba species.4

It is now known that E. histolytica and E. dispar share similar, worldwide geographical distributions and that E. dispar is about 10 times as common as E. histolytica.5 E. dispar, however, has never been associated with disease, does not elicit any specific serologic response, and can currently be considered a harmless commensal.

Is it possible to differentiate the two morphologically identical species of Entamoeba in the laboratory? Zymodyme analysis is useful, but it requires weeks in a laboratory. Polymerase chain reactions identifying specific sequences of extrachromosomal circular DNA can be used to differentiate pathogenic from nonpathogenic Entamoeba.6 Unfortunately, this test is most useful for epidemiologic surveys for which large numbers of samples can be stored for later testing and is less useful in specific clinical situations. An ELISA test has been designed that is specific to E. histolytica as it uses antibodies against species-specific adhesin.7 This test is commercially available from TECHLAB (toll-free U.S. number, 800-832-4522) and requires only about two hours to run; stool samples less than 24 hours old provide the most reliable results.

The presence of E. histolytica or E. dispar or any other agent transmitted by the feco-oral route provides a good opportunity to review the importance of food and water hygiene with travelers. Even if E. dispar is not associated with symptomatic illness, its presence does indicate that the patient ingested fecal material. All travelers should be counseled to implement excellent habits of fluid selection, food preparation, and handwashing during travel in developing countries.

References

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2. Li E, Stanley SL. Gastroenterol Clins North Am 1996; 25:471-492.

3. Reed SL. Clin Infect Dis 1995;21(Suppl 2):S182-185.

4. Diamond LS, Clark CG. J Euk Microbiol 1993;40: 340-344.

5. Hashmey R, et al. J Travel Med 1996;4:17-31.

6. Acuna-Soto R, et al. Am J Trop Med Hyg 1993;48: 58-70.

7. Haque R, et al. Am J Trop Med Hyg 1994;50:595-596.