Review of Medical Microbiology and Immunology, 13th Edition

53. Minor Protozoan Pathogens


Acanthamoeba & Naegleria






Self-Assessment Questions

Summaries of Organisms

Practice Questions: USMLE & Course Examinations

The medically important stages in the life cycle of certain minor protozoa are described in Table 53–1.

TABLE 53–1 Medically Important Stages in Life Cycle of Certain Minor Protozoa



Acanthamoeba castellanii and Naegleria fowleri are free-living amebas that cause meningoencephalitis. The organisms are found in warm freshwater lakes and in soil. Their life cycle involves trophozoite and cyst stages. Cysts are quite resistant and are not killed by chlorination.

Naegleria trophozoites usually enter the body through mucous membranes while an individual is swimming. They can penetrate the nasal mucosa and cribriform plate to produce a purulent meningitis and encephalitis that are usually rapidly fatal (Figure 53–1). Acanthamoeba is carried into the skin or eyes during trauma. Acanthamoeba infections occur primarily in immunocompromised individuals, whereas Naegleria infections occur in otherwise healthy persons, usually children. In the United States, these rare infections occur mainly in the southern states and California.


FIGURE 53–1 Naegleria fowleri—trophozoite. Arrows point to two ameba-shaped trophozoites in brain tissue. (Figure courtesy of Public Health Image Library, Centers for Disease Control and Prevention.)

Diagnosis is made by finding amebas in the spinal fluid. The prognosis is poor even in treated cases. Amphotericin B may be effective in Naegleria infections. Pentamidine, ketoconazole, or flucytosine may be effective in Acanthamoeba infections.

Acanthamoeba also causes keratitis—an inflammation of the cornea that occurs primarily in those who wear contact lenses. With increasing use of contact lenses, keratitis has become the most common disease associated with Acanthamoeba infection. The amebas have been recovered from contact lenses, lens cases, and lens disinfectant solutions. Tap water contaminated with amebas is the source of infection for lens users.


Babesia microti causes babesiosis—a zoonosis acquired chiefly in the coastal areas and islands off the northeastern coast of the United States (e.g., Nantucket Island). The sporozoan organism is endemic in rodents and is transmitted by the bite of the tick Ixodes dammini (renamed I. scapularis), the same species of tick that transmits Borrelia burgdorferi, the agent of Lyme disease. Babesia infects red blood cells, causing them to lyse, but unlike plasmodia, it has no exoerythrocytic phase. Asplenic patients are affected more severely.

The influenzalike symptoms begin gradually and may last for several weeks. Hepatosplenomegaly and anemia occur. Diagnosis is made by seeing intraerythrocytic ring-shaped parasites on Giemsa-stained blood smears. The intraerythrocytic ring-shaped trophozoites are often in tetrads in the form of a Maltese cross (Figure 53–2). Unlike the case with plasmodia, there is no pigment in the erythrocytes. The treatment of choice for mild to moderate disease is a combination of atovaquone and azithromycin. Patients with severe disease should receive a combination of quinidine and clindamycin. Exchange transfusion should also be considered in patients with severe disease. Prevention involves protection from tick bites and, if a person is bitten, prompt removal of the tick.


FIGURE 53–2 Babesia microti—trophozoites in tetrads. Arrow points to a red blood cell containing four trophozoites in a tetrad resembling a “Maltese cross.” (Figure courtesy of Dr. S. Glenn, Public Health Image Library, Centers for Disease Control and Prevention.)


Balantidium coli is the only ciliated protozoan that causes human disease (i.e., diarrhea). It is found worldwide but only infrequently in the United States. Domestic animals, especially pigs, are the main reservoir for the organism, and humans are infected after ingesting the cysts in food or water contaminated with animal or human feces. The trophozoites excyst in the small intestine, travel to the colon, and, by burrowing into the wall, cause an ulcer similar to that of Entamoeba histolytica. However, unlike the case with E. histolytica, extraintestinal lesions do not occur.

Most infected individuals are asymptomatic; diarrhea rarely occurs. Diagnosis is made by finding large ciliated trophozoites or large cysts with a characteristic V-shaped nucleus in the stool. There are no serologic tests. The treatment of choice is tetracycline. Prevention consists of avoiding contamination of food and water by domestic animal feces.


Cyclospora cayetanensis is an intestinal protozoan that causes watery diarrhea in both immunocompetent and immunocompromised individuals. It is classified as a member of the Coccidia.1

The organism is acquired by fecal–oral transmission, especially via contaminated water supplies. One outbreak in the United States was attributed to the ingestion of contaminated raspberries. There is no evidence for an animal reservoir.

The diarrhea can be prolonged and relapsing, especially in immunocompromised patients. Infection occurs worldwide. The diagnosis is made microscopically by observing the spherical oocysts in a modified acid-fast stain of a stool sample. There are no serologic tests. The treatment of choice is trimethoprim-sulfamethoxazole.


Isospora belli is an intestinal protozoan that causes diarrhea, especially in immunocompromised patients (e.g., those with acquired immunodeficiency syndrome [AIDS]). Its life cycle parallels that of other members of the Coccidia. The organism is acquired by fecal–oral transmission of oocysts from either human or animal sources. The oocysts excyst in the upper small intestine and invade the mucosa, causing destruction of the brush border.

The disease in immunocompromised patients presents as a chronic, profuse, watery diarrhea. The pathogenesis of the diarrhea is unknown. Diagnosis is made by finding the typical oocysts in fecal specimens. Serologic tests are not available. The treatment of choice is trimethoprim-sulfamethoxazole.


Microsporidia are a group of protozoa characterized by obligate intracellular replication and spore formation. As the name implies, the spores are quite small, approximately 1 to 3 µm, about the size of Escherichia coli. One unique feature of these spores is a “polar tube,” which is coiled within the spore and extrudes to attach to the human cells upon infection. The protoplasm of the spore then enters the human cell via the polar tube.

Enterocytozoon bieneusi and Encephalitozoon intestinalis are two important microsporidial species that cause severe, persistent, watery diarrhea in AIDS patients. The organisms are transmitted from human to human by the fecal–oral route. Microsporidia are also implicated in infections of the central nervous system, the genitourinary tract, and the eye. It is uncertain whether an animal reservoir exists. Diagnosis is made by visualization of spores in stool samples or intestinal biopsy samples. The treatment of choice is albendazole.


1. Regarding Acanthamoeba and Naegleria species, which one of the following is most accurate?

(A) They are free-living amebas that live in warm fresh water.

(B) Naegleria is a well-recognized cause of otitis media, primarily in children.

(C) The drug of choice for infections caused by these organisms is chloroquine.

(D) Their main clinical presentation is pneumonia acquired when water is aspirated into the lung.

2. Regarding B. microti, which one of the following is most accurate?

(A) It infects macrophages, causing them to lyse.

(B) Doxycycline is the drug of choice for babesiosis.

(C) It is transmitted by the bite of Culex mosquitoes.

(D) Seeing sporozoites within red cells supports the diagnosis of babesiosis.

(E) B. microti causes disease primarily in the northeastern region of the United States.

3. Your patient is a 10-year-old girl with a fever and a severe headache for the past 2 days. Pertinent history includes swimming in a pond near their home in rural California in August. On exam, nuchal rigidity was observed and a lumbar puncture was performed. The spinal fluid white blood cell count was 12,200 with 80% neutrophils. Microscopic examination of a wet mount of spinal fluid revealed motile trophozoites. Of the following, which one is the most likely cause?

(A) B. microti

(B) Cryptosporidium parvum

(C) N. fowleri

(D) Toxoplasma gondii

(E) Trypanosoma cruzi

4. Your patient is a 50-year-old man with a fever and shaking chills who had been vacationing 2 weeks ago on one of the islands off the coast of Massachusetts. Microscopic examination of a blood smear reveals ring-shaped trophozoites in tetrads within red blood cells. Of the following, which one is the most likely cause?

(A) B. microti

(B) Cryptosporidium parvum

(C) N. fowleri

(D) Toxoplasma gondii

(E) Trypanosoma cruzi


1. (A)

2. (E)

3. (C)

4. (A)


Brief summaries of the organisms described in this chapter begin on page 664. Please consult these summaries for a rapid review of the essential material.


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.

1 Coccidia is a subclass of Sporozoa.