Human Infection

Vector
Reservoir
Transmission
Incubation Period
Clinical Presentation
Pathogenesis
Diagnostic Tests
Management and Therapy

  *image from www.nih.go.jp/~tendo/atlas/ japanese/cyclospora.html


Vector

There is no known vector for Cyclospora. Because this species exists in the environment as an oocyst and is generally transmitted through water or food contamination, it is uncertain whether a vector is a part of the life cycle.

Reservoir

Currently, humans are the only known natural or experimental host for Cyclospora cayentanensis. Other species of Cyclospora are known to infect vertebrates such as reptiles, insectivores, and rodents.

Transmission

Because Cyclospora oocysts must undergo an environmental phase of an estimated 5 to 10 days before sporulation, it is unlikely that transmission from person to person is a major factor in infection. The vast majority of cases of cyclosporiasis in endemic areas are believed to have been transmitted through contaminated water. Transmission through fresh produce has also been documented. Recent outbreaks in the United States have been linked to raspberries, mesculin and basil. The infectious dose necessary to cause infection is unknown although it is predicted to be low. The transmissibility of Cyclospora in water is also uncertain, and would depend on the means of contamination and water treatment. Cyclospora oocysts, like Cryptosporidium oocysts, are probably highly resistant to chlorine although filtering water should be effective at removing the parasites.

Below are pictures of raspberries, mesculin and basil – items of fresh produce that have been epidemiologically linked to clustered outbreaks in the United States:


*pictures from www.cdc.gov/ncidod/emergplan/ slideset/8.htm, www.thevegetablegarden.com/ menu1.htm, www.aheb.com/garden/a-c.html

Incubation Period

The period from infection to disease ranges from 2 to 11 days, with the average being one week.

Clinical Presentation

Cyclospora infection can present with a range of symptoms. Many infections, especially in those native to endemic regions, appear to be asymptomatic. The most common disease symptom is a watery diarrhea. The average length of time for the diarrhea is more than three weeks and it can often occur in a relapsing or cyclical pattern. The main symptoms may be preceded by a flu-like illness. Associated symptoms include abdominal cramping, nausea, vomiting, flatus, bloating, D-xylose malabsorption, anorexia, weight loss, dehydration, fever, fatigue, and myalgia. The illness appears to be self-limiting, although some infections can last longer than seven weeks.

Cases of cyclosporiasis in immunocompromised hosts tend to result in more severe and prolonged illness. The rate of recurrence is increased in these individuals. Some reports have described biliary tract disease in patients with AIDS.

The clinical description of Cyclospora infection is very similar to many other gastrointestinal diseases of varying causes, which frequently leads to misdiagnosis. Cyclosporiasis is clinically indistinguishable from crytopsporidiosis, isosporiasis or microsporidia, gastrointestinal diseases caused by other parasites.

Pathogenesis

The mechanisms of Cyclospora cayentanensis pathogenesis are not fully understood. Like other known species of Cyclospora, the main site of infection of Cyclospora cayentanensis is the small intestine. The parasite’s preferential site is believed to be the jejunum, where it interferes with absorption. Studies of the gastrointestinal region of infected patients have revealed inflammation of the lamina propria, surface epithelial disarray, villous atrophy and blunting, and crypt hyperplasia of jejunal tissue. Sexual and asexual forms of Cyclospora have been found in the cytoplasm of enterocytes (intestinal epithelial cells) although it is currently unknown whether the pathogenesis of this parasite is due to enterocyte dysfunction or toxins released directly by the parasite. Recent studies have shown that there is a surprising amount of genetic diversity among certain genetic sequences. This suggests the possibility of polyparasitism, simultaneous infection with different strains of the parasite.

Diagnostic Tests

There are multiple methods for accurate detection of Cyclospora. The most common method is through examination of a wet mount (often stained) from a stool sample.

1. Microscopy – Cyclospora oocysts are 8 to 10 microns in diameter

Preparation: to maximize recovery of Cyclospora oocysts, the stool specimen should be concentrated using the Formalin-ethyl acetate technique (centrifuge for 10 minutes at 500 x g).

a. Ultraviolet epifluorescence microscopy

Cyclospora oocysts autofluoresce under UV light (with a 340-380 BP filter) and appear a neon blue.

*image from http://www.cdfound.to.it/html/cyc2.htm

b. Bright-field microscopy

This microscopy method can be used to distinguish the oocysts based on appropriate morphological features of Cyclospora (nonrefractile spheres that contain undifferentiated cytoplasm or refractile globules).

*image from http://www.cdfound.to.it/html/cyc-1.htm

c. Acid-fast stained slide

Acid fast staining is the most common laboratory method of identification. Cyclospora oocysts are variably acid fast, which means that in the same field oocysts may be unstained or stained a color from light pink to deep red. The oocysts often appear less perfectly round and wrinkled.

*image from http://www.cdfound.to.it/html/cyc-1.htm

d. Modified safranin technique

All present Cyclospora oocysts stain a reddish orange when safranin smears are heated in a microwave oven.

*image from http://www.dpd.cdc.gov/DPDx/HTML/ImageLibrary/Cyclosporiasis_il.htm

e. Trichome-stained slide

This microscopy method is not optimal for the viewing and distinguishing of Cyclospora oocysts. Oocysts appear as clear, round and somewhat wrinkled spheres of approximately 8 to 10 microns.

 

*image from http://www.med-chem.com/Para/New/cc-stain.htm

3. PCR detection of parasite DNA

This technique is still being developed but initial tests are promising. Some studies claim that cross-amplification with other coccidian parasite DNA, including other species of Cyclospora and Eimeria, is possible. More specific methods such as sequence analysis, RFLP analysis and PCR with mismatched primers might better distinguish between species. PCR can also not differentiate between sporulated and unsporulated oocysts.

 

*image from http://www.dpd.cdc.gov/DPDx/HTML/ImageLibrary/Cyclosporiasis_il.htm

4. Examination of jejunal biopsies

This technique is controversial because it is uncertain whether hematoxylin and eosin staining of the tissue allows for adequate visualization. Cyclospora at different stages of the life cycle can be found within the cytoplasm of enterocytes, while Cryptosporidium reside on the surface of the enterocytes.

* image from www.mtsinai.on.ca/familialgican/ PJSEnglish/PJSBOOK1.htm

Other Notes

Cyclospora infection is commonly confused with Cryptosporidium infection. It is necessary to distinguish between these two parasitic infections because the treatments are different.


*image from http://www.dpd.cdc.gov/DPDx/HTML/ImageLibrary/Cyclosporiasis_il.htm

This chart shows some diagnostic differences between Cryptosporidium parvum, Cyclospora cayentanensis, and Ispospora belli. Images A, C and F (the first images in each sequence) demonstrate acid fast smears. All three parasites appear variably acid fast. Ispospora appears considerably larger than the other parasites and Cyclospora oocysts are considerably larger than Cryptosporidium oocyst. The size differential can also be noted through bright-field microscopy – images B, D, and G. Both Cyclospora and Isospora appear a neon blue through epifluorescence testing while Cryptosporidium is not visible.

Management and Therapy

The only currently recognized treatment for cyclosporiasis is trimethoprim-sulfamethoxazole. In adults 160 mg trimethoprim and 800 mg sulfamethoxazole is given twice daily for 7 days. In children 5 mg/kg trimethoprim and 25 mg/kg sulfamethoxazole is given twice daily for 7 days. In immunocompromised patients recurrence is common so it is recommended that the dosing be increased to four times daily for ten days followed by continual prophylaxis three times per week. Cryptosporidium does not respond to trimethoprim-sulfamethoxazole.