E. histolytica causes amebic dysentery and liver abscess.
The life cycle of E. histolytica is shown in Figure 51–1. The life cycle has two stages: the motile ameba (trophozoite) and the nonmotile cyst (Figures 51–2A and B, 51–3, and 51–4). The trophozoite is found within the intestinal and extraintestinal lesions and in diarrheal stools. The cyst predominates in nondiarrheal stools. These cysts are not highly resistant and are readily killed by boiling but not by chlorination of water supplies. They are removed by filtration of water.
Entamoeba histolytica. Life cycle. Top blue arrow shows cysts being ingested. Within the intestine, the cyst produces trophozoites that cause amebic dysentery in the colon and can spread to the liver (most often), lung, and brain (Boxes A and B). Bottom blue arrow shows cysts and trophozoites being passed in the stool and entering the environment. Red arrow indicates survival of cysts in the environment. (Reproduced with permission from Centers for Disease Control and Prevention.)
A: Entamoeba histolytica trophozoite with one ingested red blood cell and one nucleus (circle with inner dotted line represents a red blood cell). B: E. histolytica cyst with four nuclei. C: Giardia lamblia trophozoite. D: G. lamblia cyst. E: Trichomonas vaginalis trophozoite (1200×).
Entamoeba histolytica—trophozoite. Long arrow points to trophozoite of E. histolytica. Short arrow points to the nucleus of the trophozoite. Arrowhead points to one of the six ingested red blood cells. (Reproduced with permission from Centers for Disease Control and Prevention.)
Entamoeba histolytica—cyst. Arrow points to a cyst of E. histolytica. Two of the four nuclei are visible just to the left of the head of the arrow. (Reproduced with permission from Centers for Disease Control and Prevention.)
The cyst has four nuclei, an important diagnostic criterion. Upon excystation in the intestinal tract, an ameba with four nuclei emerges and then divides to form eight trophozoites. The mature trophozoite has a single nucleus with an even lining of peripheral chromatin and a prominent central nucleolus (karyosome).
Antibodies are formed against trophozoite antigens in invasive amebiasis, but they are not protective; previous infection does not prevent reinfection. The antibodies are useful, however, for serologic diagnosis.
Pathogenesis & Epidemiology
The organism is acquired by ingestion of cysts that are transmitted primarily by the fecal–oral route in contaminated food and water. Anal–oral transmission (e.g., among male homosexuals) also occurs. There is no animal reservoir. The ingested cysts differentiate into trophozoites in the ileum but tend to colonize the cecum and colon.
The trophozoites invade the colonic epithelium and secrete enzymes that cause localized necrosis. Little inflammation occurs at the site. As the lesion reaches the muscularis layer, a typical “flask-shaped” ulcer forms that can undermine and destroy large areas of the intestinal epithelium (Figure 51–5). Progression into the submucosa leads to invasion of the portal circulation by the trophozoites. By far, the most frequent site of systemic disease is the liver, where abscesses containing trophozoites form.
Entamoeba histolytica—flask-shaped ulcer forms in colonic mucosa resulting in bloody diarrhea. (Used with permission from Dr. Mae Melvin, Centers for Disease Control and Prevention.)
Infection by E. histolytica is found worldwide but occurs most frequently in tropical countries, especially in areas with poor sanitation. About 1% to 2% of people in the United States are affected. Infection is common in men who have sex with men.
Acute intestinal amebiasis presents as dysentery (i.e., bloody, mucus-containing diarrhea) accompanied by lower abdominal discomfort, flatulence, and tenesmus. Chronic amebiasis with low-grade symptoms such as occasional diarrhea, weight loss, and fatigue also occurs. Roughly 90% of those infected have asymptomatic infections, but they may be carriers, whose feces contain cysts that can be transmitted to others. In some patients, a granulomatous lesion called an ameboma may form in the cecal or rectosigmoid areas of the colon. These lesions can resemble an adenocarcinoma of the colon and must be distinguished from them.
Amebic abscess of the liver is characterized by right-upper-quadrant pain, weight loss, fever, and a tender, enlarged liver. Right-lobe abscesses can penetrate the diaphragm and cause lung disease. Most cases of amebic liver abscess occur in patients who have not had overt intestinal amebiasis. Aspiration of the liver abscess yields brownish-yellow pus with the appearance and consistency of anchovy paste.
Diagnosis of intestinal amebiasis rests on finding either trophozoites in diarrheal stools or cysts in formed stools (see Figures 51–3 and 51–4). Diarrheal stools should be examined within 1 hour of collection to see the ameboid motility of the trophozoite. Trophozoites characteristically contain ingested red blood cells. The most common error is to mistake fecal leukocytes for trophozoites. Because cysts are passed intermittently, at least three specimens should be examined. The O&P test is insensitive, and false negatives commonly occur. Also, about half of the patients with extraintestinal amebiasis have negative stool examinations.
E. histolytica can be distinguished from other amebas by two major criteria: (1) The first is the nature of the nucleus of the trophozoite. The E. histolytica nucleus has a small central nucleolus and fine chromatin granules along the border of the nuclear membrane. The nuclei of other amebas are quite different. (2) The second is cyst size and number of its nuclei. Mature cysts of E. histolytica are smaller than those of Entamoeba coli and contain four nuclei, whereas E. coli cysts have eight nuclei.
The trophozoites of Entamoeba dispar, a nonpathogenic species of Entamoeba, are morphologically indistinguishable from those of E. histolytica; therefore, a person who has trophozoites in the stool is only treated if symptoms warrant it. Two tests are highly specific for E. histolytica in the stool: one detects E. histolytica antigen, and the other detects nucleic acids of the organism in a polymerase chain reaction (PCR)-based assay.
A complete examination for cysts includes a wet mount in saline, an iodine-stained wet mount, and a fixed, trichrome-stained preparation, each of which brings out different aspects of cyst morphology. These preparations are also helpful in distinguishing amebic from bacillary dysentery. In the latter, many inflammatory cells such as polymorphonuclear leukocytes are seen, whereas in amebic dysentery, they are not.
Serologic testing is useful for the diagnosis of invasive amebiasis. The indirect hemagglutination test is usually positive in patients with invasive disease but is frequently negative in asymptomatic individuals who are passing cysts.
The treatment of choice for symptomatic intestinal amebiasis or hepatic abscesses is metronidazole (Flagyl) or tinidazole. Hepatic abscesses need not be drained. Asymptomatic cyst carriers should be treated with iodoquinol or paromomycin.
Prevention involves avoiding fecal contamination of food and water and observing good personal hygiene such as handwashing. Purification of municipal water supplies is usually effective, but outbreaks of amebiasis in city dwellers still occur when contamination is heavy. The use of “night soil” (human feces) for fertilization of crops should be prohibited. In areas of endemic infection, vegetables should be cooked.
G. lamblia causes giardiasis. (G. lamblia is also known as G. duodenalis and G. intestinalis)
The life cycle of G. lamblia is shown in Figure 51–6. The life cycle consists of two stages: the trophozoite (Figures 51–2C and 51–7) and the cyst (Figures 51–2D and 51–8). The trophozoite is pear-shaped with two nuclei, four pairs of flagella, and a suction disk with which it attaches to the intestinal wall. The oval cyst is thick-walled with four nuclei and several internal fibers. Each cyst gives rise to two trophozoites during excystation in the intestinal tract.
Giardia lamblia. Life cycle. Top blue arrow shows cysts being ingested. Within the intestine, the cyst produces trophozoites that cause diarrhea. Bottom blue arrow shows cysts and trophozoites being passed in the stool and entering the environment. Red arrow indicates survival of cysts in the environment. (Used with permission from Dr. Alexander J. da Silva and Melanie Moser, Centers for Disease Control and Prevention.)
Giardia lamblia—trophozoite. Arrow points to a pear-shaped trophozoite of G. lamblia. (Used with permission from Dr. M. Mosher, Centers for Disease Control and Prevention.)
Giardia lamblia—cyst. Arrow points to an oval cyst of G. lamblia. (Used with permission from Dr. George Healy, Centers for Disease Control and Prevention.)
Pathogenesis & Epidemiology
Transmission occurs by ingestion of cysts in fecally contaminated food and water. Excystation takes place in the duodenum, where the trophozoite attaches to the gut wall but does not invade the mucosa and does not enter the bloodstream. The trophozoite causes inflammation of the duodenal mucosa, leading to malabsorption of protein and fat.
The organism is found worldwide; about 5% of stool specimens in the United States contain Giardia cysts. Approximately half of those infected are asymptomatic carriers who continue to excrete the cysts for years. IgA deficiency greatly predisposes to symptomatic infection.
In addition to being endemic, giardiasis occurs in outbreaks related to contaminated water supplies. Chlorination does not kill the cysts, but filtration removes them. Hikers who drink untreated stream water are frequently infected. Many species of mammals as well as humans act as the reservoirs. They pass cysts in the stool, which then contaminates water sources. Giardiasis is common in male homosexuals as a result of oral–anal contact. The incidence is high among children in day care centers and among patients in mental hospitals.
Watery (nonbloody), foul-smelling diarrhea is accompanied by nausea, anorexia, flatulence, and abdominal cramps persisting for weeks or months. There is no fever.
Diagnosis is made by finding trophozoites or cysts or both in diarrheal stools (see Figures 51–7 and 51–8). In formed stools (e.g., in asymptomatic carriers), only cysts are seen. An enzyme-linked immunosorbent assay (ELISA) test that detects Giardia antigen in the stool is also very useful. Tests for antibody in the serum are not routinely available.
If those tests are negative and symptoms persist, the string test, which consists of swallowing a weighted piece of string until it reaches the duodenum, may be useful. The trophozoites adhere to the string and can be visualized after withdrawal of the string.
The treatment of choice is either tinidazole (Tindamax) or metronidazole (Flagyl). Tinidazole is better tolerated.
Prevention involves drinking boiled, filtered, or iodine-treated water in endemic areas and while hiking. No prophylactic drug or vaccine is available.
C. hominis causes cryptosporidiosis, the main symptom of which is diarrhea. The diarrhea is most severe in immunocompromised patients (e.g., those with AIDS). Cryptosporidium parvum is the former name that is no longer used.
The life cycle of C. hominis is shown in Figure 51–9. Some aspects of the life cycle remain uncertain, but the following stages have been identified. Oocysts release sporozoites, which form trophozoites. Several stages ensue, involving the formation of schizonts and merozoites. Eventually microgametes and macrogametes form; these unite to produce a zygote, which differentiates into an oocyst. This cycle has several features in common with other sporozoa (e.g., Isospora). Taxonomically, Cryptosporidium is in the subclass Coccidia.
Cryptosporidium hominis. Life cycle. Top blue arrow shows cysts being ingested. Within the intestine, the oocyst produces trophozoites that cause diarrhea. Bottom blue arrow shows cysts being passed in the stool and entering the environment. Red arrow indicates survival of cysts in the environment. (Used with permission from Dr. Alexander J. da Silva and Melanie Moser, Centers for Disease Control and Prevention.)
Pathogenesis & Epidemiology
The organism is acquired by fecal–oral transmission of oocysts from either human sources (primarily) or from animal sources, for example, cattle (occasionally). The oocysts excyst in the small intestine, where the trophozoites (and other forms) attach to the gut wall. Invasion does not occur. The jejunum is the site most heavily infested. The pathogenesis of the diarrhea is uncertain; no toxin has been identified.
Cryptosporidia cause diarrhea worldwide. Large outbreaks of diarrhea caused by cryptosporidia in several cities in the United States are attributed to inadequate purification of drinking water. Other outbreaks are related to swimming in fecally contaminated pools and lakes. The cysts are highly resistant to chlorination but are killed by pasteurization and can be removed by filtration.
The disease in immunocompromised patients presents primarily as a watery, nonbloody diarrhea causing large fluid loss. Symptoms persist for long periods in immunocompromised patients, whereas they are self-limited in immunocompetent patients. Although immunocompromised patients usually do not die of cryptosporidiosis, the fluid loss and malnutrition are severely debilitating.
Diagnosis is made by finding oocysts in fecal smears when using a modified Kinyoun acid-fast stain (Figure 51–10). A test for Cryptosporidium antigen in the stool is also useful.
Cryptosporidium hominis—cysts. Acid-fast stain of cysts in stool. Cysts appear red on a blue background. (Reproduced with permission from Ma P, Soave R. Three-step stool examination for cryptosporidiosis in 10 homosexual men with protracted watery diarrhea; J Infect Dis. 1983 May;147(5):824-828.)
Nitazoxanide is the drug of choice for patients not infected with human immunodeficiency virus (HIV). There is no effective drug therapy for severely immunocompromised patients, but paromomycin may be useful in reducing diarrhea. There is no vaccine or other specific means of prevention. Purification of the water supply, including filtration to remove the cysts, which are resistant to the chlorine used for disinfection, can prevent cryptosporidiosis.