General Characteristics

Although isosporiasis is found worldwide, certain tropical areas in the Western Hemisphere have specific locations where endemic infections occur. These organisms infect both adults and children, and intestinal involve ment and symptoms are generally transient unless the patient is immunocompromised. I. belli has also been implicated in traveler’s diarrhea. However, unlike with Cryptosporidium spp. and C. cayetanensis, large outbreaks of isosporiasis have not been reported (see Table 1, Figure 1).

Table1. Morphologic Criteria Used to Identify Intestinal Protozoa (Coccidia, Blastocystis hominis)

Fig1. A, Immature concept of Isospora belli. B, Mature  oocyst of I. belli. (Illustration by Nobuko Kitamura.)

I. belli oocysts are passed in the stool. They are long and oval, measuring 20 to 33 µm long by 10 to 19 µm wide. Usually the oocyst contains one immature sporont, but two may be present. Continued development occurs outside the body, with the development of two mature sporocysts, each containing four sporozoites, which can be recovered from the fecal specimen. The sporulated oocyst is the infective stage that excysts in the small intestine, releasing the sporozoites, which penetrate the mucosal cells and initiate the life cycle.

Epidemiology

 I. belli oocysts are passed in the feces unsporulated or partially sporulated. Oocysts complete sporulation within 72 hours, although it may take longer, depending on the temperature. The time required for unsporulated oocysts to appear in the feces after ingestion of sporulated oocysts is 9 to 17 days. Oocyst shedding is variable and depends on the immune status of the infected individual. Oocysts can be found for 30 to 50 days in immunocompetent patients, and immunosuppressed patients may continue to shed oocysts for 6 months or longer. Chronic infections can occur, and oocysts can be shed for months to years. In one particular case, an immunocompetent individual had symptoms for 26 years, and I. belli was recovered in stool a number of times over 10 years.

I. belli is thought to be the only species of Isospora that infects humans, and no other reservoir hosts are recognized for this infection. Transmission occurs through ingestion of water or food contaminated with mature, sporulated oocysts. Sexual transmission by direct oral contact with the anus or perineum also occurs, although this mode of transmission is probably much less common. The oocysts are very resistant to environmental conditions and may remain viable for months if kept cool and moist; oocysts usually mature within 48 hours after stool passage and are then infectious.

Pathogenesis and Spectrum of Disease

Symptoms include diarrhea (most common), weight loss, abdominal colic, and fever. Stools (usually six to 10 per day) are watery to soft, foamy, and offensive smelling, suggesting a malabsorption process. Many patients have eosinophilia, recurrences are quite common, and the disease is more severe in infants and young children.

Patients who are immunosuppressed, particularly those with AIDS, often present with profuse diarrhea associated with weakness, anorexia, and weight loss. Biopsies reveal an abnormal mucosa with short villi, hypertrophied crypts, and infiltration of the lamina propria with eosinophils, neutrophils, and round cells. Physicians should consider I. belli in AIDS patients with diarrhea who have immigrated from or traveled to Latin America, are Hispanics born in the United States, are young adults, or who have not received prophylaxis with TMP-SMX for Pneumocystis infection. It has also been recommended that patients with AIDS traveling to Latin America and other developing countries be advised of the waterborne and food-borne transmission of I. belli and that chemo prophylaxis should be considered.

Extraintestinal infections in patients with AIDS have been reported. At autopsy, microscopic findings associated with I. belli infection were seen in the lymph nodes and walls of the small and large intestines, mesenteric and mediastinal lymph nodes, lymphatic channels, liver, and spleen. I. belli infections in the gallbladder epithelium and endometrial epithelium have also been reported, and oocysts have been recovered in bile specimens.

Laboratory Diagnosis

Examination of fresh material, either as the direct smear or as concentrated material, is recommended rather than the permanent stained smear. The oocysts are very pale and transparent and can easily be overlooked. The light level should be reduced, and additional contrast should be obtained with the microscope for optimal examination conditions. On the permanent stained smear, the organisms may take up excess stain and resemble helminth eggs or artifacts.

It is possible to have a positive biopsy specimen but not recover the oocysts in the stool because of the small numbers of organisms present. The oocysts are acid-fast and can also be demonstrated by using auramine rhodamine stains. Organisms tentatively identified by using auramine rhodamine stains should be confirmed by wet smear examination or acid-fast stains, particularly if the stool contains other cells or excess artifact material (more normal stool consistency). Currently, there are no commercially available nucleic acid-based methods for the detection of I. belli. However, PCR assays have been developed for the detection of the organism in stool samples.

Histology. Developmental stages of I. belli have been reported for intestinal biopsy specimens of the duodenum, jejunum, and occasionally ileum. Intestinal development tends to occur in epithelial cells, although developing stages are occasionally reported from the lamina propria or submucosa. Extraintestinal infections in patients with AIDS have been reported; the organisms become dormant as cysts in a variety of tissues, including the intestine, mesenteric lymph nodes, liver, and spleen; these cysts are called unizoite cysts. In histologic sections, these cysts are thick walled and measure 12-22 × 8-10 µm, and each contains a single dormant sporozoite/merozoite of about 8-10 × 5 µm. As immunity declines, these cysts can reactivate patent infections.

Therapy

The drug of choice to treat I. belli infection is trimethoprim sulfamethoxazole, which is given two to four times a day for 10 to 14 days. With this approach, the parasites are eliminated, the diarrhea stops, and the abdominal pain decreases within a few days. Before the use of HAART, it was recommended that patients who were HIV positive and had a CD4+ cell count below 200 cells/mm3 receive secondary prophylaxis with TMP-SMX once daily or three times a week to prevent relapse. Once the CD4 count exceeded 200 cells/mm3, prophylaxis was no longer necessary.

Prevention

Because transmission occurs through the infective oocysts, prevention includes improved personal hygiene measures and sanitary conditions to eliminate possible fecal-oral transmission from contaminated food, water, and possibly environmental surfaces.

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