Chapter 53: Minor Protozoan Pathogens

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

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.

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. Therefore, co-infection with B. microti and B. burgdorferi can occur. Babesia infects red blood cells, causing them to lyse, but unlike plasmodia, it has no exoerythrocytic phase. Asplenic patients and patients being treated with rituximab are affected more severely.

The influenza-like symptoms (e.g., fever, chills, sweats, myalgia) begin gradually and may last for several weeks. Rash typically does not occur. 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. A PCR assay for Babesia DNA is also useful.

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.

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 food and water supplies. Several outbreaks in the United States were caused by the ingestion of imported fresh produce, such as basil and 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 mm, 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.