Basics
Description
Clinical syndromes associated with Entamoeba histolytica infection
Epidemiology
- Fecal-oral transmission
- Transmission also via contaminated water and food
- The incubation period is typically 1-3 weeks but can range from a few days to months or years.
Incidence
- Amebiasis accounts for 40-50 million cases of colitis worldwide.
- 40,000-110,000 deaths annually
Prevalence
- The estimated prevalence in the United States is 4%, although there have been no recent serosurvey in developed countries.
- Worldwide distribution involving an estimated 10% or more of the world's population
- Most common in tropical areas, with infection rates as high as 20-50%
- Highest morbidity and mortality are seen in developing countries in Central America, South America, Africa, and Asia.
General Prevention
- Treatment of drinking water
- Hand washing
- Appropriate disposal of human fecal waste
- Use of condoms
- Infection-control measures: Standard precautions are recommended for the hospitalized patient.
Risk Factors
- The very young, the elderly, and patients with underlying immunosuppression or malnutrition are at highest risk for severe disease.
- Patients in whom the diagnosis should be considered include the following:
- Immigrants from or travelers to endemic areas
- Children with bloody stools or mucus in stools
- Children with hepatic abscess
- The febrile child with right upper quadrant pain and tenderness, abdominal pain, or discomfort
- The child with hepatomegaly, typically without jaundice
Pathophysiology
- E. histolytica is excreted as cysts or trophozoites in the stool of infected patients.
- Ingested cysts are unaffected by gastric acid and become trophozoites that colonize and invade the colon.
- Amebae attach to epithelial cells via a galactose/N-acetylgalactosamine (Gal/GalNac)-binding lectin.
- The parasite has the ability to lyse human epithelial cells or kill by inducing apoptosis.
- Then cytokines and chemokines released attract neutrophils, macrophages, and lymphocytes. The host immune response contributes significantly to the reduction of epithelial integrity.
- Amebae then use cysteine protease to cleave extracellular matrix proteins to invade the submucosal layers.
- The EhCPDH112 complex interacts with mucosal tight junction proteins to produce mucosal damage.
- Amebae can then disseminate directly from the intestine to the liver in up to 10% of patients. Dissemination from the liver to the lung, heart, brain, and spleen has been described.
Etiology
- E. histolytica is a nonflagellated protozoan parasite.
- Other species of the Entamoeba family are nonpathogenic, including the morphologically identical Entamoeba dispar.
Diagnosis
History
- Intestinal disease may be asymptomatic or have mild symptoms such as abdominal discomfort, flatulence, constipation, and occasionally diarrhea.
- Nondysenteric colitis is characterized by intermittent diarrhea and abdominal pain.
- Acute amebic colitis (dysenteric) is associated with grossly bloody stools with mucus, abdominal pain, and tenesmus.
Physical Exam
- Fever may be present
- Abdominal tenderness, abdominal rigidity, and rebound are variably present.
- Right upper quadrant tenderness and jaundice may be present in cases of liver abscess.
Diagnostic Tests & Interpretation
The diagnosis of amebiasis depends on the recognition of typical symptoms and routine laboratory tests.
Lab
- CBC typically reveals a leukocytosis.
- Transaminases are often not elevated.
- Occult blood is detected in stool.
- Stool samples
- Isolation and visualization
- Serial stool samples, usually 3, are recommended.
- Samples obtained within 1-2 hours of passage should be examined by wet mount and fixed in formalin and polyvinyl alcohol.
- Serial stool samples are necessary because cysts may be shed intermittently. 3 serial stool samples will detect up to 70% of patients with amebic colitis and 50% of patients with hepatic abscess.
- Stool samples should not be contaminated by urine, water, barium, enema substances, laxatives, or antibiotics because these substances may destroy or interfere with identification of the trophozoites.
- Microscopy has a sensitivity of <60% and specificity of 10-50% on a single sample.
- 2nd-generation stool antigen testing kits (commercially available) also have demonstrated excellent sensitivity and specificity comparable to real time PCR.
- Molecular testing to differentiate E. histolytica from nonpathogenic Entamoeba species is in the research phase.
- Serology
- Serum antiamebic antibodies are considered an adjunct to diagnosis.
- ~85% of patients with amebic dysentery and 99% of patients with liver amebiasis will have positive serology.
Imaging
- US, CT, or MRI of the liver may reveal liver abscess.
- In patients with hepatic amebiasis, chest x-ray may reveal elevation of the right hemidiaphragm.
Diagnostic Procedures/Other
- Note: Amebae are difficult to visualize in abscess aspirates, and substantial risk is associated with CT- or US-guided procedures, including bleeding, peritonitis secondary to spillage of amebae, or rupture of echinococcal cysts.
- Colonoscopy
Pathologic Findings
- Identification of trophozoites or cysts in the stool
- Colonic or rectal mucosa visualized by colonoscopy reveals ulcerations, and amebae can often be found around these lesions.
Differential Diagnosis
The diagnosis is often missed in children because the diagnosis is not considered in the differential. Because it is not common in the United States, amebiasis may initially be misdiagnosed as bacterial dysentery. Differential diagnosis includes the following:
- Infection
- Salmonella species
- Shigella species
- Campylobacter species
- Yersinia species
- Clostridium difficile
- Escherichia coli (enteroinvasive and enterohemorrhagic)
- Pyogenic abscess
- Echinococcal cyst
- Inflammatory bowel disease
- Crohn disease
- Ulcerative colitis
- Ischemic colitis
- Diverticulitis
- Arteriovenous malformations
- Hepatoma
Treatment
Medication
First Line
- Asymptomatic intestinal amebiasis: intraluminal agents
- Iodoquinol is the drug of choice. The recommended dosage is 30-40 mg/kg/24 h (max, 1,950 mg) PO in 3 divided doses for 20 days.
- Acute amebic colitis or extraintestinal amebiasis
- Metronidazole (a tissue-active agent) 35-50 mg/kg/24 h PO in 3 divided doses for 10 days (max, 2,250 mg/24 hr) plus a course of treatment with an intraluminal-active agent (as the preceding)
- ~1/3 of patients treated with metronidazole alone will relapse.
Second Line
- Asymptomatic intestinal amebiasis
- Diloxanide furoate (Furamide) at doses of 20 mg/kg/24 h (max, 1,500 mg/24 h) PO in 3 divided doses or paromomycin, 25-35 mg/kg/24 h PO in 3 divided doses for 7 days
- Acute amebic colitis or extraintestinal amebiasis
- 1 study has reported good efficacy using nitazoxanide in children; however, the sample size was small and the analyses combined E. histolytica and E. dispar into 1 stratum.
- However, nitazoxanide shows good activity in vitro against E. histolytica.
General Measures
- The goal of treatment is the elimination of tissue-invading trophozoites and intestinal cysts.
- The choice of treatment regimens depends on the clinical presentation.
- Agents that are active against E. histolytica are divided into 2 categories: drugs with activity against intraluminal amebae and drugs with activity against extraintestinal and invasive amebiasis.
Surgery/Other Procedures
Patients with large liver abscesses or who have failed medical therapy should be considered candidates for surgical or percutaneous drainage.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Follow-up stool examination is always necessary to ensure eradication of intestinal amebae.
- For amebic abscesses, drainage should be considered if response to medical therapy has not occurred in 4-5 days.
Prognosis
Clinical improvement is expected within 72 hours of initiation of therapy.
Complications
- Amebic liver abscess
- 2nd most common presentation of amebiasis, often not associated with amebic dysentery
- Ameboma
- Abdominal mass representing granulation tissue in the colon
- Extraintestinal manifestations of amebiasis are presumed to be a result of direct extension from liver abscesses. These include the following:
- Pericarditis
- Pleuropulmonary abscess or empyema
- Bronchohepatic fistula
- Genitourinary tract abscess
- Cerebral abscess
- Cutaneous amebiasis
- This is a rare finding in children, with ~6,510 cases reported in the literature.
- Shallow painful cutaneous ulcers in the diaper area, usually found in association with amebic colitis or dysentery.
- Epidemiologic studies from countries with high prevalence of amebiasis show an association between amebic diarrhea and poor growth. The negative effect on growth was significantly more deleterious than diarrhea caused either by Giardia or Cryptosporidium.
Additional Reading
- Bercu TE, Petri WA, Behm JW. Amebic colitis: new insights into pathogenesis and treatment. Curr Gastroenterol Rep. 2007;9(5):429-423. [View Abstract]
- Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J Med. 2003;348(16):1565-1573. [View Abstract]
- Manga ±a ML, Fern ¡ndez-D ez J, Manga ±a M. Cutaneous amebiasis in pediatrics. Arch Dermatol. 2008;144(10):1369-1372. [View Abstract]
- Mondal D, Petri WA, Sack RB, et al. Entamoeba histolytica-associated diarrheal illness is negatively associated with the growth of preschool children: evidence from a prospective study. Trans R Soc Trop Med Hyg. 2006;100(11):1032-1038. [View Abstract]
- Ravdin JI, Stauffer WM. Entamoeba histolytica (amebiasis). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, Vol 2. 6th ed. Philadelphia: Churchill Livingstone; 2005:3097-3111.
- Stauffer W, Ravdin JI. Entamoeba histolytica: an update. Curr Opin Infect Dis. 2003;16(5):479-485. [View Abstract]
- Tanyukse lM, Petri WA. Laboratory diagnosis of amebiasis. Clin Microbiol Rev. 2003;16(4):713-729. [View Abstract]
Codes
ICD09
- 006.9 Amebiasis, unspecified
- 006.0 Acute amebic dysentery without mention of abscess
- 006.3 Amebic liver abscess
- 006.2 Amebic nondysenteric colitis
- 006.4 Amebic lung abscess
- 006.8 Amebic infection of other sites
ICD10
- A06.9 Amebiasis, unspecified
- A06.0 Acute amebic dysentery
- A06.4 Amebic liver abscess
- A06.2 Amebic nondysenteric colitis
- A06.89 Other amebic infections
- A06.5 Amebic lung abscess
SNOMED
- 111910009 Amebic infection (disorder)
- 235747003 Amebic colitis
- 75119003 Amebic liver abscess (disorder)
- 55023005 Amebic nondysenteric colitis (disorder)
- 65095005 Amebic lung abscess
FAQ
- Q: How often does a liver abscess complicate intestinal amebiasis?
- A: About 10% of children with intestinal amebiasis will develop a liver abscess.
- Q: What is the best diagnostic study for a suspected amebic liver abscess?
- A: Serology is the best way to diagnose amebiasis as the cause of a liver abscess. Stool studies are usually negative at the time that a liver abscess has complicated intestinal amebiasis; thus, the yield of stool studies is low.