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E. histolytica: A formidable gastrointestinal infection
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A 23-year-old Thai man who had been working at a meat factory in the United States for the past 4 years presented to the ED with a 2-week history of abdominal pain, fever and chills. He denied any nausea, vomiting or diarrhea. A CAT scan of the abdomen revealed an 8 x 7 cm right lobe liver abscess, which was drained but resulted in no growth. Serologic testing was positive for Entamoeba histolytica antibodies.
E. histolytica is an intestinal protozoan parasite that causes amebiasis. Humans are the only host for E. histolytica, which is transmitted by fecal-oral contact. Transmission may occur directly from person to person or through contaminated food and water. Ingestion of less than 100 organisms is adequate to cause amebiasis. E. histolytica cysts are resistant to chlorine and can remain stable in the environment for weeks to months, making it a formidable food and waterborne infection.
Amebiasis affects approximately 50 million people around the world each year, leading to 100,000 deaths. It is likely the second-leading protozoan cause of death after malaria. Infection is most frequent in tropical climates, particularly in developing countries with poor sanitation. However, amebiasis still occurs in the U.S. Amebiasis is not considered a nationally notifiable parasitic disease by the CDC, but the prevalence of infection in the U.S. has been estimated to be 4%. It is the third most common parasitic infection in the U.S., following giardiasis and cryptosporidiosis. One study reviewing national death certificate data from 1990 to 2007 identified a total of 134 deaths, the majority occurring among U.S.-born individuals.
Travelers and immigrants from endemic areas are at greater risk for developing amebiasis. Other risk factors include people living in institutions with poor sanitary conditions and those who practice oral-anal sex. Patients at increased risk for severe disease are those at the extremes of age; pregnant women; those who are malnourished or immunocompromised; and those who have chronic comorbid conditions like diabetes.
Presentations of amebiasis range from asymptomatic infection to severe invasive disease. After ingestion of E. histolytica, the cysts hatch into trophozoites within the intestine. The motile trophozoites then have the opportunity to invade intestinal mucosa, which results in amebic colitis. Patients with amebic colitis typically present with gradually worsening bloody diarrhea and general abdominal pain. Fever with colitis is rarely present. The onset of symptoms is usually within a few weeks but may occur days to years after exposure, which helps distinguish it from bacterial causes of dysentery. Complications of intestinal amebiasis include necrotizing colitis, perforation, peritonitis, toxic megacolon, fistula formation and ameboma intraluminal mass formation.
Less commonly, E. histolytica trophozoites travel outside the intestine. E. histolytica infects the liver most frequently because the trophozoites use the portal vein to spread from the intestine. Liver abscesses are 10 times more likely in adult men. Patients with liver abscesses usually present with fever, chills, right upper quadrant pain, and tender hepatomegaly. The abscess generally is located in the right lobe of the liver as a single lesion, and if aspirated, the necrotic yellow-brown contents of the abscess have been described as “anchovy paste.” Metastatic infection is a serious complication of amebic liver abscesses, which may rarely spread to sites such as the lung, heart and brain.
There are a variety of tests offered for the diagnosis of amebiasis. Although widely available, stool ova and parasite examination lacks sensitivity (10%-50%) and is unable to distinguish E. histolytica from the morphologically identical, nonpathogenic species E. dispar. Stool antigen tests provide much higher sensitivity (80%) for intestinal amebiasis, but many of these tests still cross-react with E. dispar. A rapid point-of-care stool antigen test was recently approved by the FDA in 2017. The new Quik Chek assay by TechLab is specific for E. histolytica and can provide results in 30 minutes. Serologic testing is most valuable for patients with extraintestinal disease; the sensitivity for amebic liver abscess is over 90%. However, serology cannot differentiate between past and current infection, so it is less useful in endemic areas with high rates of past exposure. PCR tests have the highest sensitivity and specificity (both > 95%) and can be used with various sample types, such as stool or liver abscess aspirate. Unfortunately, PCR testing is not available in most labs.
Over 90% of patients with E. histolytica are asymptomatic. It is important to distinguish E. histolytica from E. dispar because the E. histolytica is treated even in the absence of symptoms, whereas the E. dispar requires no treatment. Asymptomatic carriers of E. histolytica are at risk for developing invasive amebiasis. It is estimated that 4% to 10% of carriers will develop invasive disease within 1 year if not treated. Treatment of asymptomatic E. histolytica also prevents further transmission.
Drug therapy for amebiasis can be divided into two categories: luminal amebicides and tissue amebicides (see Table). The luminal agents paromomycin, iodoquinol and diloxanide furoate act within the intestine and have minimal absorption. Asymptomatic colonization is treated with luminal amebicide monotherapy. The first-line luminal agent is paromomycin. Paromomycin should be given with meals and may cause gastrointestinal side effects such as nausea, abdominal cramping and diarrhea.
Because luminal agents are not systemically absorbed, invasive amebiasis is treated with tissue amebicides, primarily nitroimidazoles. Metronidazole or tinidazole are most commonly used for both amebic colitis and liver abscess. Tinidazole has a longer half-life and seems to be better tolerated compared with metronidazole. Secnidazole and ornidazole can also be used, but these drugs are not available in the U.S. for amebiasis. Intestinal E. histolytica may remain in 40% to 60% of patients, so nitroimidazole therapy should be followed by paromomycin to eradicate luminal infection. Paromomycin should be given after rather than at the same time as nitroimidazole therapy because the diarrheal side effect of paromomycin may make it difficult to determine if a patient is responding to therapy.
Alinia (nitazoxanide, Romark Pharmaceuticals) is a broad-spectrum antiparasitic agent approved by the FDA for the treatment of giardiasis and cryptosporidiosis but has activity against many other intestinal protozoa and helminths. Clinical experience for treating amebiasis is limited, but it appears to be an effective treatment option for mild to moderate intestinal disease. A 2007 randomized, placebo-controlled trial in Egypt evaluated nitazoxanide therapy in 34 patients with intestinal amebiasis and 17 patients with liver amebiasis. All patients with liver involvement responded to therapy, and 32 (94%) patients with intestinal amebiasis had complete resolution of symptoms. Because human trials are limited, a 2011 study used a mouse model to directly compare the efficacy of current treatment options. Although metronidazole and nitazoxanide were both potent agents against E. histolytica in vitro, metronidazole had superior efficacy in vivo.
It is important to note that some antiparasitic drugs are not readily available but may be obtained through the CDC Drug Service, WHO or specialty compounding pharmacies. For those of you who use The Sanford Guide to Antimicrobial Therapy as a resource, this guide provides a list of sources for hard-to-find antiparasitic agents that can be useful when trying to obtain some of these medications.
Drainage of liver abscesses may be necessary if there is a high risk for rupture or if patients are not responding to drug therapy alone. Antibiotics may also be added in these patients because there is a possibility for bacterial coinfection with amebic liver abscesses.
Amebiasis can primarily be prevented by proper sanitation. Travelers to endemic areas should take precautions regarding food and water, such as drinking only bottled or boiled water and avoiding fresh produce that has already been peeled or washed with local water. Contacts of infected individuals should practice good hand hygiene. There is no available vaccine at this time to protect against E. histolytica infection. However, vaccination in animal models have conferred at least partial immunity. Development of this vaccine is still a work in progress.
- References:
- Becker S, et al. Am J Trop Med Hyg. 2011;doi:10.4269/ajtmh.2011.10-0580.
- CDC. Amebiasis: Entamoeba histolytica infection. https://www.cdc.gov/parasites/amebiasis/index.html. Accessed February 5, 2018.
- Drugs for Parasitic Infections. Treat Guidel Med Lett. 2013;11(Suppl):e2.
- Gunther J, et al. Am J Trop Med Hyg. 2011;doi:10.4269/ajtmh.2011.11-0288.
- Petri WA, Haque R. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. 2014;doi:10.1016/B978-1-4557-4801-3.00274-5.
- Pritt BS, et al. Mayo Clin Proc. 2008;doi:10.4065/83.10.1154.
- Rossignol JF, et al. Trans R Soc Trop Med Hyg. 2007;101:1023-1031.
- For more information:
- Lauren Bricker, PharmD, is a PGY-2 infectious diseases pharmacy resident at Mercy Medical Center in Des Moines, Iowa.
- Jeff Brock, PharmD, MBA, BCPS AQ-ID, is an infectious disease pharmacy specialist at Mercy Medical Center. He can be reached at: JBrock@mercydesmoines.org.
Disclosures: Bricker and Brock report no relevant financial disclosures.