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Cystoisosporiasis

[Cystoisospora belli (syn. Isospora belli)]

Causal Agents

The coccidian parasite, Cystoisospora belli, infects the epithelial cells of the small intestine, and is the least common of the three intestinal coccidia that infect humans.


Life Cycle

lifecycle

At time of excretion, the immature oocyst contains usually one sporoblast (more rarely two)The number 1. In further maturation after excretion, the sporoblast divides in two (the oocyst now contains two sporoblasts); the sporoblasts secrete a cyst wall, thus becoming sporocysts; and the sporocysts divide twice to produce four sporozoites eachThe number 2. Infection occurs by ingestion of sporocysts-containing oocysts: the sporocysts excyst in the small intestine and release their sporozoites, which invade the epithelial cells and initiate schizogonyThe number 3. Upon rupture of the schizonts, the merozoites are released, invade new epithelial cells, and continue the cycle of asexual multiplicationThe number 4. Trophozoites develop into schizonts which contain multiple merozoites. After a minimum of one week, the sexual stage begins with the development of male and female gametocytesThe number 5. Fertilization results in the development of oocysts that are excreted in the stoolThe number 1.

Geographic Distribution

Worldwide, especially in tropical and subtropical areas. Infection occurs in immunodepressed individuals, and outbreaks have been reported in institutionalized groups in the United States.

Clinical Presentation

Infection causes acute, nonbloody diarrhea with crampy abdominal pain, which can last for weeks and result in malabsorption and weight loss. In immunodepressed patients, and in infants and children, the diarrhea can be severe. Eosinophilia may be present (differently from other protozoan infections).

Cystoisospora belli oocysts.

 

The oocysts of C. belli are large (25 to 30 µm) and have a typical ellipsoidal shape. When excreted, they are immature and contain one sporoblast. The oocyst matures after excretion: the single sporoblast divides in two sporoblasts, which develop cyst walls, becoming sporocysts, which eventually contain four sporozoites each. Cystoisospora will autofluoresce under ultraviolet (UV) microscopy.
	Figure A

Figure B: Immature oocyst of C. belli stained with safranin, containing a single sporoblast.

	Figure B

Figure B: Immature oocyst of C. belli stained with safranin, containing a single sporoblast.

	Figure C

Figure C: Immature oocyst of C. belli stained with acid-fast, showing a single sporoblast.

	Figure D

Figure D: Oocyst of C. belli viewed under ultraviolet (UV) microscopy, showing two sporoblasts.

Cystoisospora belli oocysts.

	Figure A

Figure A: Immature oocyst of C. belli in an unstained wet mount showing a single sporoblast.

	Figure B

Figure B: Immature oocyst of C. belli in an unstained wet mount showing two sporoblasts.

	Figure C

Figure C: Same oocyst as in Figure A but viewed under differential interference contrast (DIC).

	Figure D

Figure D: Same oocyst as in Figure B but viewed under ultraviolet (UV) fluorescent micrscopy.

	Figure E

Figure E: Same oocyst as in Figures A and C but viewed under ultraviolet (UV) fluorescent micrscopy.

	Figure F

Figure F: Same oocyst as in Figures B and D but viewed under UV microscopy.

Cystoisospora belli oocysts, stained with hematoxylin and eoisin (H&E).

	Figure A

Figure A: Oocyst of C. belli in the epithelial cells of a mammalian host, stained with H&E (yellow arrow).

	Figure B

Figure B: Oocyst of C. belli in the epithelial cells of a mammalian host, stained with H&E (yellow arrow).

Laboratory Diagnosis

Microscopic demonstration of the large, typically shaped oocysts, is the basis for diagnosis. Because the oocysts may be passed in small amounts and intermittently, repeated stool examinations and concentration procedures are recommended. If stool examinations are negative, examination of duodenal specimens by biopsy or string test (Enterotest®) may be needed. The oocysts can be visualized on wet mounts by microscopy with bright-field, differential interference contrast (DIC), and epifluorescence. They can also be stained by modified acid-fast stain.

Bench Aids

Treatment Information

Trimethoprim-sulfamethoxazole (TMP-SMX), sold under the trade names Bactrim*, Septra*, and Cotrim*, is the medication of choice for Cystoisospora infection. The typical treatment regimen for adults is TMP 160 mg plus SMX 800 mg (one double-strength tablet), orally, twice a day, for 7 to 10 days.

Expert consultation is recommended if the patient is immunosuppressed, for example, has AIDS. Such patients may need to be treated longer and/or with higher daily doses. This is an example of an alternative regimen of TMP-SMX for adults: one double-strength tablet of TMP-SMX, orally, four times a day, for up to 3 or 4 weeks. Patients with AIDS also may need maintenance therapy (secondary prophylaxis) with TMP-SMX to prevent recurrence of symptomatic infection.

Only limited data are available regarding potential alternatives to TMP-SMX. Patients who are allergic to (or are intolerant of) TMP-SMX usually are treated with pyrimethamine. For adults, the typical daily dose of pyrimethamine is in the range of 50 to 75 mg. This daily dose is given orally, either once a day or divided into 2 separate doses. For example, 50 mg can be given in one dose, or 25 mg can be given twice a day. Pyrimethamine can suppress the bone marrow. To help prevent this, patients treated with pyrimethamine also take leucovorin, orally, in a daily dose in the range of 10 to 25 mg. Folinic acid is another name for leucovorin.

Ciprofloxacin is a second-line alternative. It is less effective than TMP-SMX but might have some activity against Cystoisospora. For adults, the treatment regimen is 500 mg, orally, twice a day, for 7 days.

Trimethoprim–sulfamethoxazole

Trimethoprim–sulfamethoxazole (TMP–SMX) is available for human use in the United States.

Trimethoprim–sulfamethoxazole (TMP–SMX) is in pregnancy category C. TMP–SMX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. TMP-SMX should be avoided near-term because of the potential for hyperbilirubinemia and kernicterus in the newborn.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Trimethoprim–sulfamethoxazole (TMP–SMX) is excreted in breast milk. TMP–SMX generally is compatible with breastfeeding of healthy, full-term infants after the newborn period. However, TMP-SMX generally should be avoided by women when nursing infants who are premature, jaundiced, ill, or stressed, or who have glucose-6-phosphate dehydrogenase deficiency.

The safety of trimethoprim–sulfamethoxazole (TMP–SMX) in children has not been systematically evaluated. Use in children less than 2 months of age generally is not recommended.

Ciprofloxacin

Ciprofloxacin is available for human use in the United States.

Ciprofloxacin is in pregnancy category C. Data on the use of ciprofloxacin in pregnant women are limited, although the available evidence suggests that the risk for congenital anomalies is low. Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Ciprofloxacin is excreted in breast milk. The American Academy of Pediatrics classifies ciprofloxacin as usually compatible with breastfeeding, whereas the World Health Organization recommends avoiding ciprofloxacin while breastfeeding. Ciprofloxacin should be used during lactation only if the potential benefit justifies the potential risk to the fetus.

Available evidence is conflicting regarding the potential for growth defects and arthropathies in exposed children. Use of ciprofloxacin in children requires assessment of potential risks and benefits.

* Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.

References

 

DPDx is an education resource designed for health professionals and laboratory scientists. For an overview including prevention and control visit www.cdc.gov/parasites/.

  • Page last reviewed: May 3, 2016
  • Page last updated: May 3, 2016
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