Review of Medical Microbiology and Immunology, 13th Edition

51. Intestinal & Urogenital Protozoa

CHAPTER CONTENTS

Introduction

INTESTINAL PROTOZOA

Entamoeba

Giardia

Cryptosporidium

UROGENITAL PROTOZOA

Trichomonas

Self-Assessment Questions

Summaries of Organisms

Practice Questions: USMLE & Course Examinations

INTRODUCTION

In this book, the major protozoan pathogens are grouped according to the location in the body where they most frequently cause disease. The intestinal and urogenital protozoa are described in this chapter, and the blood and tissue protozoa are described in Chapter 52.

(1) Within the intestinal tract, three organisms—the ameba Entamoeba histolytica, the flagellate Giardia lamblia, and the sporozoan Cryptosporidium hominis—are the most important.

(2) In the urogenital tract, the flagellate Trichomonas vaginalis is the important pathogen.

(3) The blood and tissue protozoa are a varied group consisting of the flagellates Trypanosoma and Leishmania and the sporozoans Plasmodium and Toxoplasma. The important opportunistic lung pathogen Pneumocystis will be discussed in this group, although there is molecular evidence that it should be classified as a fungus.

The major and minor pathogenic protozoa are listed in Table 51–1.

TABLE 51–1 Major and Minor Pathogenic Protozoa

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Although immigrants and Americans returning from abroad can present to physicians in the United States with any parasitic disease, certain parasites are much more likely to occur outside the United States. The features of the medically important protozoa, including their occurrence in the United States, are described in Table 51–2.

TABLE 51–2 Features of Medically Important Protozoa

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The medically important stages in the life cycle of the intestinal protozoa are described in Table 51–3.

TABLE 51–3 Medically Important Stages in Life Cycle of Intestinal Protozoa

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INTESTINAL PROTOZOA

ENTAMOEBA

Diseases

Entamoeba histolytica causes amebic dysentery and liver abscess.

Important Properties

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 B51–3, and 51–4). The trophozoite is found within the intestinal and extraintestinal lesions and in diarrheal stools. The cyst predominates in non-diarrheal 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.

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FIGURE 51–1 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. (Provider: Centers for Disease Control and Prevention.)

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FIGURE 51–2 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×).

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FIGURE 51–3 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. (Provider: Centers for Disease Control and Prevention.)

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FIGURE 51–4 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. (Provider: 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.

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FIGURE 51–5 Entamoeba histolytica—flask-shaped ulcer forms in colonic mucosa resulting in bloody diarrhea. (Provider: Centers for Disease Control and Prevention/Dr. Mae Melvin.)

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.

Clinical Findings

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.

Laboratory Diagnosis

Diagnosis of intestinal amebiasis rests on finding either trophozoites in diarrheal stools or cysts in formed stools (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.

Treatment

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

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.

GIARDIA

Disease

Giardia lamblia causes giardiasis.

Important Properties

The life cycle of G. lamblia is shown in Figure 51–6. The life cycle consists of two stages: the trophozoite and the cyst (Figures 51–2C and D, and 51–7). 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.

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FIGURE 51–6 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. (Provider: Centers for Disease Control and Prevention/Dr. Alexander J. da Silva and Melanie Moser.)

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FIGURE 51–7 Giardia lamblia—trophozoite. Arrow points to a pear-shaped trophozoite of G. lamblia. (Provider: Centers for Disease Control and Prevention/Dr. M. Mosher.)

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.

Clinical Findings

Watery (nonbloody), foul-smelling diarrhea is accompanied by nausea, anorexia, flatulence, and abdominal cramps persisting for weeks or months. There is no fever.

Laboratory Diagnosis

Diagnosis is made by finding trophozoites or cysts or both in diarrheal stools (Figure 51–7). 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.

Treatment

The treatment of choice is metronidazole (Flagyl) or quinacrine hydrochloride.

Prevention

Prevention involves drinking boiled, filtered, or iodine-treated water in endemic areas and while hiking. No prophylactic drug or vaccine is available.

CRYPTOSPORIDIUM

Disease

Cryptosporidium hominis causes cryptosporidiosis, the main symptom of which is diarrhea. The diarrhea is most severe in immunocompromised patients (e.g., those with acquired immunodeficiency syndrome [AIDS]). Cryptosporidium parvum is the former name that is no longer used.

Important Properties

The life cycle of C. hominis is shown in Figure 51–8. 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.

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FIGURE 51–8 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. (Provider: Centers for Disease Control and Prevention/Dr. Alexander J. da Silva and Melanie Moser.)

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.

Clinical Findings

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.

Laboratory Diagnosis

Diagnosis is made by finding oocysts in fecal smears when using a modified Kinyoun acid-fast stain (Figure 51–9). A test for Cryptosporidium antigen in the stool is also useful.

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FIGURE 51–9 Cryptosporidium hominis—cysts. Acid-fast stain of cysts in stool. Cysts appear red on a blue background. (Provider: Centers for Disease Control and Prevention/J Infect Dis. 1983;147(5):824–8.)

Treatment & Prevention

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.

UROGENITAL PROTOZOA

TRICHOMONAS

Disease

Trichomonas vaginalis causes trichomoniasis.

Important Properties

T. vaginalis is a pear-shaped organism with a central nucleus and four anterior flagella (Figures 51–2E and 51–10). It has an undulating membrane that extends about two-thirds of its length. It exists only as a trophozoite; there is no cyst form.

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FIGURE 51–10 Trichomonas vaginalis—trophozoite. Arrows point to two trophozoites. (Provider: Centers for Disease Control and Prevention.)

Pathogenesis & Epidemiology

The organism is transmitted by sexual contact, and hence there is no need for a durable cyst form. The primary locations of the organism are the vagina and the prostate. It is found only in humans; there is no animal reservoir.

Trichomoniasis is one of the most common infections worldwide. Roughly 25% to 50% of women in the United States harbor the organism. The frequency of symptomatic disease is highest among sexually active women in their thirties and lowest in postmenopausal women. Asymptomatic infections are common in both men and women.

Clinical Findings

In women, a watery, foul-smelling, greenish vaginal discharge accompanied by itching and burning occurs. Infection in men is usually asymptomatic, but about 10% of infected men have urethritis.

Laboratory Diagnosis

In a wet mount of vaginal (or prostatic) secretions, the pear-shaped trophozoites have a typical jerky motion (Figure 51–10). Neutrophils are often seen in the fluid. There is no serologic test.

Treatment & Prevention

The drug of choice is metronidazole (Flagyl) for both partners to prevent reinfection. Maintenance of the low pH of the vagina is helpful. Condoms limit transmission. No prophylactic drug or vaccine is available.

SELF-ASSESSMENT QUESTIONS

1. Regarding E. histolytica, which one of the following is most accurate?

(A) E. histolytica causes “flask-shaped” ulcerations in the colon mucosa.

(B) Domestic animals such as dogs and cats are the main reservoir of E. histolytica.

(C) In the microscope, E. histolytica is recognized by having two sets of paired flagella.

(D) E. histolytica infections are limited to the intestinal mucosa and do not spread to other organs.

(E) The infection is typically acquired by the ingestion of the trophozoite in contaminated food and water.

2. Regarding G. lamblia, which one of the following is most accurate?

(A) The drug of choice for giardiasis is chloroquine.

(B) In giardiasis, ova and parasite (O&P) analysis of the stool reveals sporozoites in the feces.

(C) G. lamblia produces an enterotoxin that increases cyclic AMP within the enterocyte, resulting in diarrhea.

(D) G. lamblia infection is acquired by ingestion of food or water contaminated with human feces only (i.e., there is no animal reservoir for this organism).

(E) Infection by G. lamblia occurs principally in the small intestine, frequently resulting in the malabsorption of fat and foul-smelling, frothy, fat-containing stools.

3. Regarding C. hominis, which one of the following is most accurate?

(A) Humans are the only reservoir for C. hominis.

(B) Microscopic examination of the diarrheal stool reveals both red cells and white cells.

(C) Laboratory diagnosis involves seeing cysts of the organism in an acid-fast stain of the stool.

(D) C. hominis is typically acquired by the ingestion of trophozoites in contaminated food or water.

(E) In immunocompromised patients, such as AIDS patients with a very low CD4 count, disseminated disease occurs that typically involves the brain and meninges.

4. Regarding Trichomonas vaginalis, which one of the following is most accurate?

(A) The drug of choice for trichomoniasis is metronidazole.

(B) Domestic animals, such as dogs and cats, are the principal reservoir of the organism.

(C) T. vaginalis is typically acquired by contact with the cysts of the organism during sexual intercourse.

(D) Laboratory diagnosis typically involves the detection of a greater than fourfold rise in the titer of IgA antibody.

(E) The asymptomatic male sex partner of a woman with T. vaginalis infection should not be treated because asymptomatic men are rarely the source of the organism.

5. Your patient is a 30-year-old woman who returned from traveling in Eastern Europe 1 week ago. While on the trip, she experienced anorexia, nausea but no vomiting, and abdominal bloating. For the last 2 days, she has had explosive watery diarrhea. An examination of her stool revealed pear-shaped, flagellated, motile organisms. Of the following, which one is the most likely cause of this infection?

(A) C. hominis

(B) E. histolytica

(C) G. lamblia

(D) T. vaginalis

6. Regarding the patient in Question 5, which one of the following is the best antibiotic to treat the infection?

(A) Chloroquine

(B) Metronidazole

(C) Nifurtimox

(D) Praziquantel

(E) Stibogluconate

7. Your patient is a 30-year-old Peace Corps volunteer who has recently returned from Central America. She now has fever and right-upper-quadrant pain. She reports that she had bloody diarrhea 2 months ago. A CT scan reveals a radiolucent area in the liver that is interpreted to be an abscess. Aspiration of material from the abscess was performed. Microscopic examination revealed motile, nonflagellated trophozoites with ameboid movement. Of the following, which one is the most likely cause of this infection?

(A) C. hominis

(B) E. histolytica

(C) G. lamblia

(D) T. vaginalis

8. Your patient is a 30-year-old man with persistent watery diarrhea for 2 weeks. He is HIV antibody positive with a CD4 count of 10. Routine stool culture revealed no bacterial pathogen. Ova and parasite analysis revealed cysts that stained red in an acid-fast stain. Of the following, which one is the most likely cause of this infection?

(A) C. hominis

(B) E. histolytica

(C) G. lamblia

(D) T. vaginalis

ANSWERS

1. (A)

2. (E)

3. (C)

4. (A)

5. (C)

6. (B)

7. (B)

8. (A)

SUMMARIES OF ORGANISMS

Brief summaries of the organisms described in this chapter begin on page 661. Please consult these summaries for a rapid review of the essential material.

PRACTICE QUESTIONS: USMLE & COURSE EXAMINATIONS

Questions on the topics discussed in this chapter can be found in the Parasitology section of PART XIII: USMLE (National Board) Practice Questions starting on page 710. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.