Pathogenic Amebas

ENTAMOEBA HISTOLYTICA & ENTAMOEBA DISPAR

Essentials of Diagnosis

Patient living in or having traveled to endemic area increases risk.
Frequent loose stools with blood and mucus.
Demonstration of cyst or trophozoite on stool wet mount or in biopsy specimen.
Serology positive within 7-10 days of infection, may remain positive for years after infection resolved.
Monoclonal antibodies and polymerase chain reaction emerging; may help differentiate E histolytica and E dispar.

General Considerations

Epidemiology

There are numerous distinct species of ameba within the genus Entamoeba, and the majority of these do not cause disease in humans. E histolytica is a pathogenic species that is capable of causing disease, such as colitis or liver abscess, in humans. E dispar is prevalent and is indistinguishable from E histolytica by conventional laboratory methods. E dispar exists in humans in only an asymptomatic carrier state and does not cause colitis.

It has been estimated that 10% of the world’s population is infected with either E histolytica or E dispar. Of those infected, < 10% will manifest symptomatic disease. Infection is prevalent in Central and South America, southern and western Africa, the Far East, and India. Pregnant women, children, those of lower socioeconomic status, and those who live in crowded conditions or areas with poor sanitation are more likely to be infected.

In the United States, the prevalence of E histolytica and E dispar is much lower, approximately 4%. The risk factors for infection are the same as those above. In addition, those who travel to an endemic area, homosexual males, and institutionalized persons are at increased risk of infection.

Microbiology

E histolytica exists in one of two forms, a cyst or a trophozoite. Infection is generally through fecal-oral spread with ingestion of the cyst form, which is resistant to killing by the low pH of the stomach. Within the small bowel, the cyst divides into trophozoites, which then colonize the large intestine. The trophozoites may subsequently encyst and be shed into the stool. Once shed, they may remain viable for weeks to months.

During acute colitis, trophozoites may be shed into the stool. Unlike the cyst, the trophozoite cannot live outside the host because it is rapidly killed by poor environmental conditions and, if ingested, is degraded in the acid stomach environment.

Pathogenesis

E histolytica infection is enhanced by the production of several virulence factors. Production of proteolytic enzymes allows the trophozoite to disrupt tissue planes and invade the colonic epithelium. The trophozoite may ascend the portal venous structures to produce hepatic infection, and obstruction of the portal vessels by the trophozoites may produce hepatic necrosis. The trophozoites are able to lyse neutrophils through a contact-dependent mechanism that protects the trophozoite from ingestion and causes local tissue damage by release of the neutrophil’s enzymes. Trophozoites are also resistant to complement-mediated lysis and produce adherence lectins that aid in the binding of the trophozoite to colonic epithelium, thereby facilitating invasion of the epithelium. These adherence proteins also aid in the contact-dependent lysis of tissue and white cells.

CLINICAL SYNDROMES

Infection with E histolytica causes multiple syndromes, which range from asymptomatic intestinal infection to fulminant colitis. In addition, E histolytica may cause disease at several nonintestinal sites, including the liver, lung, brain, and genitourinary tract. The clinical syndromes caused by E histolytica are outlined in Box 1.

Intestinal Disease

Amebic Liver Abscess

PATHOGENIC FREE-LIVING AMEBAS

ACANTHAMOEBA INFECTION

Amebas of the genus Acanthamoeba live as cysts and trophozoites in soil and in water. They can cause several disease syndromes in human hosts, including encephalitis, keratitis, and infections of the skin that resemble deep fungal infections. In addition, they can infect other human tissues and cause a granulomatous reaction. These amebas may be carried in an asymptomatic nasal carrier state. Immunocompromised patients, such as transplant recipients and HIV-infected persons, are at increased risk of contracting disease. Diving in warm water may increase infection rates.

The encephalitis caused by Acanthamoeba is a chronic, focal, necrotizing infection characterized by granuloma formation (granulomatous encephalitis). Patients usually present with the insidious onset of focal neurological deficits, fevers, headache, meningismus, seizures, and mental status changes. Common focal deficits include visual disturbances and ataxia. Diagnosis is difficult and is often made only at autopsy. Tissue biopsy specimens may provide diagnosis. Cerebrospinal fluid lymphocytosis may be present, but the organism has not been isolated from cerebrospinal fluid. Granulomatous encephalitis leads to death, with an average survival from the onset of symptoms of 40 days. No treatment is effective. Imidazole antifungal agents, amphotericin B, neomycin, flucytosine, sulfonamides, pentamidine, and propamidine have been used without success.

Acanthamoeba species cause keratitis, and > 200 cases have been described in the United States since the early 1970s. Risk factors include use of contact lenses, exposure to contaminated water, and trauma to the cornea. After exposure, patients typically note a foreign body sensation that is followed by eye pain, visual change, tearing, and conjunctivitis. Progression of disease may lead to blindness. The disease is frequently misdiagnosed initially as herpes simplex virus or bacterial keratitis. Correct diagnosis is made by demonstration of the organism on corneal scrapings or biopsy material. Treatment requires surgical debridement followed by a minimum of 3-4 weeks of medical therapy, which consists of topical treatment with propamidine, Neosporin, and miconazole. Other therapies are topical polyhexmethylene biguanide or the combination of topical miconazole and oral itraconazole.

NAEGLERIA FOWLERI INFECTION

Naegleria fowleri is a free-living ameba that causes a primary meningoencephalitis. It may live in warm water areas, including lakes, hot springs, mud puddles, and swimming pools. Most infections are in children or young adults and manifest 5-15 days after exposure to an infected water source. The organism invades the meninges through the cribiform plate, a process facilitated by diving in deep water. Those infected may have a viral prodrome with nausea, vomiting, headache, and malaise and rapidly progress to coma and death within 2-3 days. Most patients have meningeal signs.

Diagnosis must be suspected early, because, even with prompt treatment, there are only four documented survivors of this infection. Primary amebic meningoencephalitis should be considered in those with a viral prodrome rapidly progressing to coma. Patients typically have leukocytosis. Lumbar puncture should be performed with caution, as increased intracranial pressure raises the risk of herniation. Cerebrospinal fluid will show many erythrocytes and typical leukocyte counts of 400-25,000/uL, with 50-100% neutrophils. Protein may be mildly elevated, and glucose is normal to slightly low. If no bacteria are seen on Gram stain of a purulent cerebrospinal fluid, a wet mount should be examined for amebic trophozoites. The specimen should not be refrigerated or centrifuged, because this reduces the ameba’s motility and makes trophozoites difficult to distinguish from the many leukocytes.

Treatment of primary amebic meningoencephalitis is generally unsuccessful. The documented survivors received intravenous and intrathecal amphotericin B. One patient also received miconazole, rifampin, and sulfisoxazole. Laboratory studies with a rabbit model have shown synergy between amphotericin B and rifampin or tetracycline. Intrathecal administration of antinaegleria antibody has also improved survival in animal models.

BOX 1. Clinical Features of Amebiasis

Intestinal

Hepatic

Extrahepatic

More Common

Asymptomatic > (90%)
Frequent loose stools with blood and mucus
Abdominal pain
Right-upper-quadrant pain, right shoulder pain, or both
Fever in first 2 weeks
Weight loss
Cough, even in absence of pulmonary disease
Pleuropulmonary (cough, pleuritic chest pain, “anchovy paste” effusion)
Peritoneal (abdominal pain — ranges from mild to acute)

Less Common

Fever
Volume depletion
Ameboma
Megacolon
Perforation
Diarrhea
Hepatomegaly
Pericardial (fever, chest pain, congestive heart failure, tamponade)
Cerebral (change in mental status, focal neurologic deficits)
Genitourinary (painful ulcers with profuse discharge)

BOX 2. Treatment of Amebiasis in Adults

Asymptomatic Cyst

Passage

Intestinal Disease

Hepatic

Extrahepatic

First Choice

Luminal agent — diloxanide furoate, 500 mg PO three times daily × 10 d

Paromomycin, 500 mg PO three times daily × 10 d

Iodoquinol, 650 mg PO three times daily × 20 d
Metronidazole, 750 mg PO three times daily × 10 d
Followed by luminal agent
Metroindazole,750 mg PO three times daily or 500 mg IV every 6 h × 10 d
Followed by luminal agent
Drug therapy is the same as for hepatic disease
Consider drainage

Alternative

Tetracycline, 250 mg three times daily × 10 d
Erythromycin, 500 mg PO four
Tinidazole, 50 mg/kg per day × 3 d (not available in the United States
Followed by luminal agent
Tinidazole or ornidazole, 2 g PO once (not available in the United States)
Followed by luminal agent times daily × 10 d

BOX 3. Treatment of Amebiasis in Children

Asymptomatic

Cyst Passage

Intestinal Disease

Hepatic

Extrahepatic

First Choice

Luminal agent — diloxanide furoate, 20 mg/kg/d in 3 divided doses × 10 d

Paromomycin, 30 mg/kg/d in 3 divided doses × 10 d

Iodoquinol, 20-40 mg/kg/d in 3 divided doses × 20 d
Metronidazole, 30-50 mg/kg/d in 3 divided doses × 5-10 d
Followed by luminal agent
Metronidazole, 30-50 mg/kg/d in 3 divided doses PO or IV × 5-10 d
Followed by luminal agent
Drug therapy is the same as for hepatic disease
Consider drainage

Alternative

Alternative drugs and dosages not established

BOX 4. Prevention of Control of Amebiasis

Prophylactic Measures

Effective sanitation and clean water supply
Cysts resistant to chlorine, killed by boiling water and iodine
Travelers to endemic areas should avoid unpeeled fruits and vegetables and untreated water

Isolation Precautions

Vaccines under development