OVERVIEW: What every practitioner needs to know

Are you sure your patient has amebiasis? What are the typical findings for this disease?

Amebiasis is caused by the parasite Entamoeba histolytica. The most common symptom of infection is diarrhea. Dysentery can also develop. Abdominal pain or cough can be symptoms if there is a liver abscess, which is a rare complication in children (most common in young men).

What other disease/condition shares some of these symptoms?

Almost any cause of diarrhea could mimic amebic diarrhea. If amebic dysentery develops, the differential diagnosis is narrowed to Salmonella, Shigella, and Campylobacter species, and enterohemorrhagic Escherichia coli.

What caused this disease to develop at this time?

Predisposing factors include travel to or immigration from an area of endemic transmission (e.g., regions of developing countries such as the Indian subcontinent, Southeast Asia, sub-Saharan Africa, Mexico, and parts of Central and South America). Steroids or other immunosuppressive medications can activate a latent infection with
Entamoeba histolytica.

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What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Amebic diarrhea or amebic colitis is best diagnosed by detection of a parasite antigen or DNA in stool (by fecal antigen detection or polymerase chain reaction (PCR), respectively). Serologic studies for antibodies to E histolytica are supportive. Amebic liver abscess is best diagnosed by an imaging study of the liver (ultrasonography, computed tomography [CT], or magnetic resonance imaging [MRI]).

Would imaging studies be helpful? If so, which ones?

Imaging studies are not helpful in diagnosing amebic colitis. Amebic liver abscess is best diagnosed by an imaging study of the liver (ultrasonography, CT, or MRI). All three are equally sensitive, and none can distinguish a pyogenic abscess from an amebic abscess.

Confirming the diagnosis

Amebiasis should be considered in the differential diagnosis of diarrhea, dysentery, colitis, liver abscess (and rarely liver abscess extending to the pleura or pericardia), or brain abscess. A helpful clue to diagnosis is a history of travel or residence in a developing country where amebiasis is endemic.

If you are able to confirm that the patient has this disease, what treatment should be initiated?

The drug of first choice for amebiasis is metronidazole. It is administered for children in doses of 35-50 mg/kg/d orally in three divided doses for 7-10 days.

Alternatively, tinidazole 50 mg/kg/d (maximum of 2 g daily) orally in one dose for 3 days can be given. As neither of these drugs reliably eliminate intestinal carriage of
E. histolytica, treatment must be followed with either iodoquinol 30-40 mg/kg/d (maximum 2 g) PO in 3 doses x 20 days or paromomycin 25-35 mg/kg/d PO in 3 doses x 7 days.

What are the adverse effects associated with each treatment option?

Metronidazole and tinidazole are carcinogenic in rodents and should be used only with caution in pregnant women.

Metronidazole and tinidazole are otherwise well tolerated (tinidazole is better tolerated than metronidazole in general), but adverse reactions include nausea, anorexia, vomiting, a metallic taste, less commonly peripheral neuropathy, and rarely, central nervouse system (CNS) toxicity including ataxia.

The safety of iodoquinol in pregnancy is not known. The toxicity of iodoquinol, which is generally well tolerated, includes diarrhea, nausea, rash, and rare optic neuritis or peripheral neuropathy.

Paromomycin administered orally is not absorbed in significant amounts and is likely safe in pregnancy. Given orally, the most common toxicity is diarrhea.

What are the possible outcomes of amebiasis?

Amebic dysentery and colitis are more serious illnesses with mortality of approximately 2%. Should toxic megacolon develop, medical therapy alone may fail and surgical removal of affected bowel may be required.

The most feared outcome is development of an amebic liver abscess, which is rare in children. An amebic liver abscess can extend to the pleural or pericardial spaces and rarely result in hematogenous dissemination to the brain. Medical therapy is effective in the majority of cases and can be lifesaving.

What causes this disease and how frequent is it?

Amebiasis is caused by infection with the parasite E histolytica. Infection is by fecal-oral exposure and usually occurs in developing countries where water, sanitation, and hygiene are suboptimal.

Amebic diarrhea is most common from birth through the preschool years and after that is unusual. In contrast, amebic liver abscess is most common in men between the ages of 20 and 40 years. Malnourishment is a risk factor. A mutation in the leptin receptor (Q223R) is associated with increased susceptibility to infection.

How do these pathogens/genes/exposures cause the disease?

The parasite invades through the colonic epithelium to cause disease.

What complications might you expect from the disease or treatment of the disease?

Amebic diarrhea can be complicated by the development of dysentery, colitis, and toxic megacolon. It can also be complicated by an amebic liver abscess, although this is more common in adult men than in children. Amebic liver abscess can be complicated by amebic pleural empyema and pericardial effusion, and rarely, brain abscess.

Are additional laboratory studies available, even some that are not widely available?

Stool antigen detection or PCR with adjunctive use of amebic serologic tests are the cornerstones of diagnosis. Colonoscopy with biopsy to visualize trophozoites (by periodic acid-Schiff [PAS] stain or immunohistochemical analysis) and aspiration of a liver abscess with detection of the parasite by PCR can also be useful diagnostic tests.

How can this disease be prevented?

Infection can be prevented by appropriate hygienic measures. Malnutrition increases risk.

What is the evidence?

Haque, R, Huston, CD, Hughes, M. “Current concepts: amebiasis”. N Engl J Med. vol. 348. 2003. pp. 1565-7. (Review of diagnosis and management of amebiasis.)

Ali, IKM, Hossain, MB, Roy, S. ” infections in children, Bangladesh”. Emerg Infect Dis. vol. 9. 2003. pp. 580-4. (Controversy over whether E. moshkovskii causes disease.)

Haque, H, Mollah, NU, Ali, IKM. “Diagnosis of amebic liver abscess and intestinal infection with the TechLab II antigen detection and antibody tests”. J Clin Microbiol. vol. 38. 2000. pp. 3235-3239. (Fecal antigen detection and use of serologic tests for diagnosis for amebiasis.)

Haque, R, Roy, S, Siddique, A. “Multiplex real-time PCR assay for detection of and spp”. Am J Trop Med Hyg. vol. 76. 2007. pp. 713-7. (Fecal PCR for diagnosis of amebiasis.)

Barwick, R, Uzicanin, A, Lareau, S. “Outbreak of amebiasis in Tbilisi, Republic of Georgia, 1998”. Am J Trop Med Hyg. vol. 67. 2002. pp. 623-31. (Waterborne outbreak of amebiasis.)

Blessmann, J, Van Linh, P, Nu, PA. “Epidemiology of amebiasis in a region of high incidence of amebic liver abscess in central Vietnam”. Am J Trop Med Hyg. vol. 66. 2002. pp. 578-83.

Hung, CC, Deng, HY, Hsiao, WH. “Invasive amebiasis as an emerging parasitic disease in patients with human immunodeficiency virus type 1 infection in Taiwan”. Arch Intern Med. vol. 165. 2005. pp. 409-15.

Powell, SJ, MacLeod, I, Wilmot, AL. “Metronidazole in amoebic dysentery and amoebic liver abscess”. Lancet. vol. 2. 1966. pp. 1329-1331. (Classic article on the use of metronidazadole for amebiasis.)

Blessmann, J, Tannich, E. “Treatment of asymptomatic intestinal Entamoeba histolytica infection”. N Engl J Med. vol. 347. 2002. pp. 1384-1384. (Demonstration of effectiveness of treatment.)

McAuley, JB, Herwaldt, BL, Stokes, SL. “Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years' experience in the United States”. Clin Infect Dis. vol. 15. 1992. pp. 464-8. (Use of diloxanide for asymptomatic cyst carriers.)

McAuley, JB, Juranek, DD. “Paromomycin in the treatment of mild-to-moderate intestinal amebiasis”. Clin Infect Dis. vol. 15. 1992. pp. 551-2. (Use of paromomycin for amebiasis.)

Ongoing controversies regarding etiology, diagnosis, treatment

There is a second species of Entamoeba, E. moshkovskii, which may cause diarrhea, but this is not certain (Koch postulates have not been confirmed).