Chapter 346. Cyclosporiasis

Cyclospora cayetanensis is a coccidian parasite that causes acute and chronic diarrhea in both immunocompetent and immunocompromised hosts. Cyclospora is phylogenetically related to other coccidian parasites, including Cryptosporidium, Isospora, Toxoplasma, and Sarcocystis. Initially described as cyanobacteria-like (blue-green algae) bodies in the stools of patients with prolonged diarrhea, anorexia, and fatigue,1Cyclospora species are now known to be ubiquitous, infecting a variety of animals, including reptiles, insectivores, and rodents. However, Cyclospora cayetanensis is the only species that is known to infect humans.2,3 Although the organism has been recovered in the stool of affected individuals from numerous regions—including North America, Central America, South America, Caribbean Islands, eastern Europe, South Africa, Southeast Asia, India, Nepal, Peru, and Haiti—infection appears to be most common in tropical and subtropical countries.4

Cyclosporiasis in developed countries is associated with international travel and waterborne or food-borne outbreaks. For example, Cyclospora has caused a waterborne outbreak among house staff in Chicago5 and is a leading cause of persistent diarrhea among travelers to Nepal in spring and summer.6 In the United States and Canada, infections have been linked to imported fresh produce such as raspberries, blackberries, basil, and baby lettuce leaves.7 Guatemalan raspberries have been associated with about 50 outbreaks from 1995 to 2000.7,8 More recently, fresh snow peas from Guatemala were associated with an outbreak of cyclosporiasis in a residential facility in Pennsylvania.9 The use of untreated or poorly treated water for irrigating crops, applying fertilizers, and washing and processing foods has been implicated as a source of contamination for fruits and vegetables.10 Cyclosporiasis associated with recreational exposure to water, especially swimming pools, has also been reported.11,12

The oocysts of C. cayetanensis are spherical, about 8 to 10 μm in size and surrounded by a thick wall.10 They are smaller than Isospora belli and twice the size of Cryptosporidiumparvum. Infection is initiated by the ingestion of the sporulated oocysts. During excystation, sporozoites are released and undergo asexual (merogony and schizogony) and sexual reproduction (gametogony) within the gastrointestinal epithelium.13 Oocysts are unsporulated, and are thus noninfectious, when freshly passed in the stool. Sporulation occurs in the environment in about 1 to 2 weeks. The oocysts can persist in food, in water, and in the environment. Washing fruits and vegetables may not be sufficient to remove the oocysts.14

Clinical Manifestations

C. cayetanensis infects both immunocompetent and immunocompromised hosts. The incubation period is estimated to be 1 to 14 days, with an average of 7 days.7 Infection with Cyclospora may be asymptomatic, may manifest as mild to moderate self-limiting diarrhea (usually in the healthy host), or may be protracted and severe. In the immunocompetent host, the mean duration of diarrheal symptoms ranges from 10 to 25 days in outbreak settings.7,15 In endemic infections and international travelers, mean duration of symptoms seems to be longer, about 6 to 7 weeks,7,16 but these differences may be secondary to host factors and delay in diagnosis and treatment. In the immunocompromised host, the diarrheal illness is usually prolonged with periods of remission and relapse, and may last for a few days to several months. Diarrhea is characteristically watery and associated with nausea, anorexia, abdominal cramps, and bloating. Profound fatigue and weight loss are usually reported. Fever is not common.

In the HIV-infected patient, Cyclospora causes symptoms that are indistinguishable from that of cryptosporidiosis and isosporiasis. Acalculous cholecystitis may also occur in AIDS patients infected with Cyclospora.17

Diagnosis

Cyclospora oocysts are visualized in wet mounts of stools as unsporulated, refractile spheres measuring 8 to 10 μm by light or phase microscopy. The oocyst wall exhibits bright blue autofluorescence when viewed by ultraviolet epifluorescence microscopy.18 Concentration of stools by either formalin-ether sedimentation or sucrose flotation has been employed to maximize detection of oocysts.18,19 Safranin staining enhances the outline of the membrane, and the oocyst is variably acid-fast by modified Ziehl-Nielsen stain.18,20-22Cyclospora is not visualized by Gram, Giemsa, or hematoxylin-eosin staining. In addition to stool, duodenal aspirates or intestinal biopsy may also contain the parasite. Amplification of DNA from C. cayetanensis by polymerase chain reaction is promising, but its use is currently limited to research settings.23-25 The combination of history of exposure, clinical disease, and demonstration of oocyst in the stool constitutes diagnosis of infection.

Treatment

In the immunocompetent patient, the illness is self-limiting. Therapy with trimethoprim-sulfamethoxazole (TMP-SMX) results in resolution of symptoms and in decrease in oocyst shedding. A 7-day course of oral TMP-SMX at 160 mg TMP plus 800 mg SMX for adults and 5 mg/kg TMP plus 25 mg/kg SMX twice daily for children is usually sufficient.26,27 In the HIV-infected patient, recurrent episodes are prevented using prophylaxis with trimethoprim-sulfamethoxazole 3 days a week.28 Agents effective against other enteric pathogens (such as albendazole, azithromycin, norfloxacin, tinidazole, quinacrine, nalidixic acid, and diloxanide furoate) have been reported to be ineffective against Cyclospora oocysts. Although less effective than TMP-SMX, ciprofloxacin and nitazoxanide may be suitable alternative agents. A randomized, open-label trial comparing the efficacy of TMP-SMX and ciprofloxacin in HIV patients with chronic diarrhea secondary to either cyclosporiasis or isosporiasis was performed in Haiti.27 The study showed resolution of diarrhea in 100% of patients who received TMP-SMX versus 87% of those who were on ciprofloxacin. Ninety-five percent of those on TMP-SMX versus 70% of those on ciprofloxacin had negative stools at day 7. Nitazoxanide has been investigated as a broad antiparasitic agent in the treatment of mixed parasitic infections in 121 children in Mexico, of whom 3% harbor Cyclospora.29 In this study, the efficacy rates reported for nitazoxanide against cyclosporiasis ranged from 71% to 87%.