Chapter 350. Isosporiasis

Isospora belli is another coccidian parasite of the phylum Apicomplexa that causes human isosporiasis. I belli is worldwide in distribution but is more common in tropical and subtropical regions, especially Haiti, Mexico, Brazil, El Salvador, tropical Africa, the Middle East, and Southeast Asia.1 The parasite causes diarrhea in both immunocompetent and immunocompromised children and adults. In the United States, sporadic outbreaks (mostly waterborne) of isosporiasis have been reported among institutionalized patients and daycare centers.2,3 It has been recognized as a cause of diarrhea among travelers to endemic areas; immigrants; and persons immunocompromised by hematologic malignancy, steroid use, or HIV infection.1,4-7 In persons with AIDS, low CD4 cell count (especially < 50 cells/μL), multiple infections, and poor hygiene have been noted as risk factors.8,9 Transmission occurs primarily by the fecal-oral route, but sexual transmission has also been implicated among men who have sex with men.10

After the host ingests the mature sporulated oocyst, excystation releases sporozoites in the proximal small bowel.11 Occasionally, sporozoites leave the intestinal tract to infect extraintestinal sites.12,13 However the sporozoites typically invade the enterocytes of duodenum and jejunum and mature into trophozoites. The trophozoites then mature into merozoites, which undergo further maturation by either asexual replication (schizogony or merogony) or sexual replication (gametogony). Gametogony produces the immature unsporulated oocyst that is passed in the stool.6 The oocyst ripens in 24 to 48 hours into the infectious form or the mature sporulated oocyst. The oocyst remains viable in a cool, moist environment for months.

Clinical Manifestations

Clinically, isosporiasis is indistinguishable from other coccidian infection such as cryptosporidiosis and cyclosporiasis. It usually causes self-limiting diarrhea in the immunocompetent host and protracted, severe diarrhea in the immunocompromised adult and child. Diarrhea may be acute or chronic. Watery stool, crampy abdominal pain, and weight loss are characteristic symptoms of isosporiasis. Other patients may have flulike symptoms, nausea, and vomiting. Fecal blood and leukocytes are absent. However, Charcot-Leyden crystals and, occasionally, mucus may be present in the stool.1 Peripheral eosinophilia is not uncommon.14,15 Severe wasting, malabsorption, lactose intolerance, and steatorrhea have been reported, particularly in the immunosuppressed patient. Extraintestinal presentations such as acalculous cholecystitis and involvement of the lymph nodes, liver, or spleen are rare but have been reported in severely immunosuppressed individuals infected with HIV.12,13,16,17

Diagnosis

Diagnosis of I belli infection is established by identifying the oocyst in feces or by visualizing the intracellular stages of the parasite in biopsy specimens of the small bowel or other sites. Isospora can be visualized in the stool by direct fecal smears, but concentration techniques such as flotation or sedimentation methods enhance detection. Modified acid-fast or auramine-rhodamine stains are commonly used to identify the oocysts of Isospora and other coccidian parasites found in feces.1,4,18 Freshly shed oocysts are oval and large (10–20 μm by 20–33 μm in size) and contain one or two sporocysts. Similar to Cyclospora species, I belli oocysts also exhibit autofluorescence under UV illumination.4,19 Because of the small number of the parasite and intermittent shedding, intestinal biopsy may be needed for diagnosis. Infection with I belli usually remains confined to the small intestine, particularly in the villi. The histopathologic findings of the intestinal mucosa include mild to moderate villous atrophy and crypt hyperplasia.11 The lamina propia is infiltrated with inflammatory cells, especially eosinophils. Routine histological staining (hematoxylin-eosin) of the intestinal tissue demonstrates the organism in parasitophorous vacuoles. I belli appear rounded, elongated, or banana-shaped, and appear pale when stained; the parasite is usually located in the subnuclear region of the mucosal lining.

Treatment

The drug of choice for isosporiasis is trimethoprim-sulfamethoxazole (TMP-SMX; TMP at 160 mg and SMX at 800 mg) given four times a day for 7 to 10 days. In patients with AIDS, secondary prophylaxis with TMP-SMX (160 mg and 800 mg, respectively) three times a week or sulfadoxine (500 mg) and pyrimethamine (25 mg) weekly has been proven to decrease recurrence.20 The patient’s symptoms generally improve within 72 hours of initiating therapy. Ciprofloxacin (500 mg twice a day)21 or pyrimethamine (75 mg a day, along with folic acid)22 may be administered in patients with sulfa drug allergy, but these may be less effective than TMP-SMX. Secondary prophylaxis with ciprofloxacin (500 mg once a day) or pyrimethamine (25 mg a day) follows the primary treatment. There is currently little data on the use of nitazoxanide for isosporiasis.23-25