Amebiasis is the infection of the human gastrointestinal tract by Entamoeba histolytica
, a protozoan parasite that is capable of invading the intestinal mucosa and may spread to other organs, mainly the liver. Entamoeba dispar
, an ameba morphologically similar to E. histolytica
that also colonizes the human gut, has been recognized recently as a separate species with no invasive potential (8
). The acceptance of E. dispar
as a distinct but closely related protozoan species has had profound implications for the epidemiology of amebiasis, since most asymptomatic infections found worldwide are now attributed to this noninvasive ameba.
Currently, there is no low-cost laboratory test available for the differentiation of E. histolytica
from E. dispar
infections. The development of this valuable diagnostic tool for use in clinical laboratories and large-scale epidemiological studies has been made a priority (8
) and is the subject of intense research (2
). Preliminary data obtained from the application of these methods confirm the presence of E. dispar
in most asymptomatic amebic infections, although E. histolytica
asymptomatic colonization is not uncommon (19
). Of note, the prevalence rates of both species in different geographical areas is still difficult to estimate due to the small number of samples analyzed.
Invasive amebiasis due to E. histolytica
is more common in developing countries. In areas of endemic infection, a variety of conditions including ignorance, poverty, overcrowding, inadequate and contaminated water supplies, and poor sanitation favor direct fecal-oral transmission of amebas from one person to another. Being responsible for approximately 70 thousand deaths annually, amebiasis is the fourth leading cause of death due to a protozoan infection after malaria, Chagas' disease, and leishmaniasis and the third cause of morbidity in this organism group after malaria and trichomoniasis, according to recent World Health Organization estimates (177
The motile form of E. histolytica, the trophozoite, lives in the lumen of the large intestine, where it multiplies and differentiates into the cyst, the resistant form responsible for the transmission of the infection. Cysts are excreted in stools and may be ingested by a new host via contaminated food or water. The parasite excysts in the terminal ileum, with each emerging quadrinucleate trophozoite giving rise to eight uninucleated trophozoites. Trophozoites may invade the colonic mucosa and cause dysentery and, through spreading via the bloodstream, may give rise to extraintestinal lesions, mainly liver abscesses.
Depending on the affected organ, the clinical manifestations of amebiasis are intestinal or extraintestinal. There are four clinical forms of invasive intestinal amebiasis, all of which are generally acute: dysentery or bloody diarrhea, fulminating colitis, amebic appendicitis, and ameboma of the colon. Dysenteric and diarrheic syndromes account for 90% of cases of invasive intestinal amebiasis. Patients with dysentery have an average of three to five mucosanguineous evacuations per day, with moderate colic pain preceding discharge, and they have rectal tenesmus. In patients with bloody diarrhea, evacuations are also few but the stools are composed of liquid fecal material stained with blood. While there is moderate colic pain, there is no rectal tenesmus. Fever and systemic manifestations are generally absent. These syndromes constitute the classic ambulatory dysentery and can easily be distinguished from that of bacterial origin, where the patient frequently complains of systemic signs and symptoms such as fever, chills, headache, malaise, anorexia, nausea, vomiting, cramping abdominal pain, and tenesmus (reviewed in reference 89
Although E. histolytica
can infect almost every organ of the body, the most frequent form of extraintestinal amebiasis is the amebic liver abscess. This condition, which results from the migration of trophozoites from the colon to the liver through the portal circulation, is 10 times more common in adults than in children and 3 times more frequent in males than in females (144
). In general, the onset is abrupt, with pain in the right hypochondrium radiating toward the right shoulder and scapular area. The pain usually increases with deep breathing, with coughing, and while stepping on the right foot during walking. When the abscess is localized to the right lobe, symptoms include an irritative cough that is sometimes productive and a pleuritic type of chest pain. Abscesses in the upper left lobe can cause epigastric, sometimes dyspneic pain, at times spreading to the base of the neck and to one or both shoulders. Fever between 38 to 40°C is found in 85 to 90% of patients with amebic liver abscess. The patient commonly has chills and profuse sweating in the afternoon and at night. Other symptoms include anorexia, nausea, vomiting, diarrhea (with or without blood), and dysentery. On physical examination, the cardinal sign of amebic liver abscess is painful hepatomegaly. Digital pressure and fist percussion will often produce intense pain in the liver region. On palpation, the liver is soft and smooth, in contrast to the rough, hard, irregular character of the liver in patients with cirrhosis and hepatocarcinoma. Jaundice is present in 8% of the patients who respond well to treatment. When jaundice is severe, multiple abscesses should be suspected. Diarrhea or dysentery is seen in fewer than one-third of patients. Complications of amebic liver abscess include perforation to the pericardial space, pleura, or peritoneal cavity (reviewed in reference 89
The diagnosis of invasive intestinal amebiasis is still based on the microscopic identification of E. histolytica
trophozoites in rectal smears or recently evacuated stools and on the results of rectosigmoidoscopy. Trophozoites are most likely to be found in the bloody mucus and in the yellowish exudate covering the mucosal ulcerations obtained during rectosigmoidoscopy. Diagnostic problems arise when only cysts are identified in stools of healthy or diarrheic individuals. A commercially available laboratory test based on the identification of specific E. histolytica
antigens in stool (60
) is able to discriminate E. histolytica
from E. dispar
cysts (W. A. Petri, unpublished observations). However, the high cost and lack of knowledge of this test have hindered its use in clinical laboratories, especially in countries where amebiasis is endemic. Until these new diagnostic tests are widely available to clinical laboratories, these samples should be reported as containing E. histolytica/E. dispar
The diagnosis of amebic liver abscess is sometimes difficult. In areas of endemic infection or when there is a history of travel to such places, amebic abscess should be suspected in patients with spiking fever, weight loss, and abdominal pain in the upper right quadrant or epigastrium and in patients with tenderness in the liver area. The presence of leukocytosis, a high alkaline phosphatase level, and an elevated right diaphragm suggest a hepatic abscess. The diagnosis is confirmed by ultrasonography or by computed tomography (CT) scans. The CT scan is the most precise method for identifying hepatic abscesses, especially when they are small, and following intravenous injection of contrasting agents, it is of great value in the differential diagnosis of other focal lesions of the liver (144
). The high cost of this method, however, limits its use to cases when there are doubts about the diagnosis.
Serological tests for antiamebic antibodies are positive in approximately 75% of patients with invasive colonic amebiasis and in over 90% of patients with amebic liver abscesses. Of all tests available, the Centers for Disease Control and Prevention has chosen the enzyme immunoassay as its standard serological reference test for amebiasis. However, in areas of endemic infection, the high prevalence of antiamebic antibodies in the general population reduces the usefulness of serological tests for diagnosis (reviewed in reference 89
The powerful lytic activity of E. histolytica, for which the parasite was named, has inspired a variety of approaches aimed at understanding the pathogenesis of invasive amebiasis. Most studies have focused on a single factor in an attempt to dissect the multiple mechanisms used by the parasite that ultimately result in tissue destruction. The aim of the present review is to provide an overview of the pathological lesions of human intestinal amebiasis and to discuss recent advances in the study of the molecular mechanisms of amebic pathogenicity.