Cyclospora

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Background

Cyclospora cayetanensis (8-10 µm in diameter), a coccidian protozoan parasite, produces an intestinal infection in nonimmune persons that is ultimately self-limited (lasting up to 7-9 wk) and characterized by cyclical diarrhea (explosive at times; up to numerous times per day), accompanied by fatigue, malaise, anorexia, nausea, weight loss, and abdominal cramping and interspersed with periods of remission. It may be preceded by a flulike prodrome. Low-grade fever and malabsorption (as demonstrated by a D-xylose test) may occur. The diarrhea may continue for weeks to months if left untreated. Cyclospora infection affects both immunocompetent and immunocompromised individuals, the latter potentially more severely (ie, chronic, relapsing, protracted symptoms). The only consistently effective treatment is with trimethoprim-sulfamethoxazole (TMP-SMZ).

Cyclospora was first reported in Papua New Guinea in 1979 as an oocystlike body found in 3 patients with intestinal infections. From 1986-1991, several reports described diarrhea associated with a large " Cryptosporidium " or cyanobacteriumlike bodies in both immunocompetent and immunosuppressed patients from North, Central, and South America; the Caribbean; Nepal; India; and Southeast Asia. Shlim et al reported on the largest series of cases (55) from the CIWEC Clinic Travel Medicine Center in Katmandu, Nepal.[1]

In 1993, in Lima, Peru, Ortega et al characterized and clarified remaining taxonomic issues for C cayetanensis.[2] Also in 1993, a prospective study of 1042 stool specimens in patients with diarrhea at the Lahey Clinic in Massachusetts yielded 3 patients with Cyclospora infection. In the late spring and early summer of 1996, an outbreak affecting approximately 1450 individuals (70% laboratory confirmed) was described in Canada and the United States.[3] Since then, numerous reports have documented its endemicity in 27 countries around the world (see Table).

Table 1. Epidemiology of C cayetanensis *


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See Table

Transmission occurs primarily through ingesting contaminated food (eg, fruits, vegetables) and water. No documented human-to-human transmission exists.

Pathophysiology

Characteristic of coccidia (phylum Apicomplexa), sporozoites of Cyclospora within the sporocyst have a membrane-bound nucleus and micronemes.

Cyclospora undergo both sexual and asexual reproduction. They appear microscopically as nonrefractile, double-walled spheres 8-10 µm in diameter. On a modified acid-fast stain, the organism stains variably acid-fast because some organisms resist staining ("ghosts"). Cyclospora fluoresces blue under ultraviolet light.

Cyclospora is a small bowel pathogen. After ingestion, Cyclospora oocysts excyst in the GI tract and invade small bowel epithelia, where they undergo asexual division followed by sexual division and produce mature oocysts that are shed in the stool.

Grossly, moderate to severe erythema of the distal duodenum is observed in patients with Cyclospora infection. Distal duodenal histopathological findings include acute and chronic inflammation, reactive hyperemia with vascular dilatation and villous capillary congestion, parasitophorous vacuoles that contain both asexual and sexual forms, crypt hyperplasia, epithelial disarray, and partial villous atrophy. Electron micrographs have demonstrated intracellular particles similar to sporozoites.

Abnormal findings on lactulose or mannitol studies or studies of both have demonstrated intestinal barrier disruption. Abnormal findings on D-xylose studies have demonstrated malabsorption. The nature of the immune response to Cyclospora is not clear, and only a few observations can currently be made. Patient sera have demonstrated Cyclospora -specific antibodies. Long-term expatriates tend to have fewer recurrences than short-term expatriates. In Haiti, patients with AIDS have recurrent disease.[4]

C cayetanensis infection occurs only in humans (ie, not in other animals). Of the 16 known Cyclospora species that infect animals (primates, other mammals, reptiles), none infects humans. Therefore, no animal reservoir for C cayetanensis is known or suspected. Cyclospora does not survive in biosolids (soil-like residue removed from sewage during the treatment process) secondary to heat of the process. Cyclospora has been demonstrated in source waters in several countries.[5] It has also been isolated from wastewater in Tunisia and in Arizona.[6, 7]

In endemic countries, soil contact is an important risk factor for children younger than 2 years. Oocysts can survive in water for 2 months at 39.2°F (4°C) and for 7 days at 98.6°F (37°C). Heating them at 140°F (60°C) for 60 minutes prevents sporulation. Freezing them at -0.4°F (-18°C) prevents sporulation. Desiccation for 15 minutes ruptures the oocyst wall. They are resistant to chlorine disinfection at standard water treatment levels. Pesticides at recommended levels (fungicides: Captan 50% WP, benomyl 50% WP, zineb 75% WP; insecticides: malathion 25% WP, diazinon 4E 47.5%) do not affect sporulation. Washing contaminated vegetables does not completely remove all of the sporocysts.

In endemic countries, the prevalence (1-15%) varies with the season (usually highest in spring and early summer) and from year to year in the same locale. Children (< 10-20 y, depending on the study) account for about 70% of infections, and 72-94% of these children are asymptomatic. Some adults in endemic countries have asymptomatic infections as well but do not excrete many oocysts. These observations suggest the possibility of a carrier state, but the certainty of this is far from demonstrated. Although more is becoming known about the biology of C cayetanensis, it remains unclear how the organism persists in the environment.

Life cycle of Cyclospora

Humans ingest sporulated oocysts (the infectious stage) of C cayetanensis, which only infects humans. The oocyst excysts in the small intestine, usually in the jejunum, and invades the intestinal epithelial cells. The next process is schizogony, which begins with the formation of a trophozoite that grows into a mature schizont that contains 8-12 merozoites, which are then released, presumably by cell rupture, to invade other epithelial cells and repeat the process. These merozoites are called type I meronts, which are asexual forms.

After several cycles of type I schizogony, type II meronts (sexual forms) develop, with each cell containing 4 merozoites. After invading epithelial cells, some of these form single macrogametes and others divide multiple times to form microgametes. When released, a microgamete fertilizes a macrogamete, which develops into a zygote. The zygote, in turn, develops into an oocyst with an environmentally resistant wall. The oocyst passes into the environment in the feces, as a nonsporulated noninfectious oocyst.

Consequently, human-to-human transmission does not occur. During infection, best evidence suggests that oocysts are continuously excreted. In the environment, the oocyst sporulates, becoming infectious for humans. During sporulation, the sporont divides into 2 sporocysts, each containing 2 sporozoites. Time course in the environment is days to weeks. In culture, 10-20% of sporonts have completed the process in 5 days. In other experimental studies, sporulation at ambient temperature occurs in 7-12 days. The preferred temperature is 78.8-86°F (26-30°C). Contamination of food or drinking water leads to human ingestion and infection. The infectious inoculum is small but has not been precisely quantitated.

Cyclosporiasis has been demonstrated to be seasonal in Guatemala (May through August), Haiti (January through March or April), Nepal (May through August), and Peru (December through May), often disappearing for months at a time.

Epidemiology

Frequency

United States

C cayetanensis causes an estimated 16,264 cases of foodborne illness in the United States each year out of the estimated 76 million cases of foodborne illness overall (325,000 hospitalizations; 5,000 deaths). No deaths have been reported secondary to Cyclospora infection (CDC data).[8]

International

C cayetanensis has been reported as endemic in at least 27 countries, mostly tropical (see Table).[9, 10, 11, 12, 13]

Mortality/Morbidity

Cyclospora infection is not considered a fatal disease. No reported deaths have been directly attributed to it in the United States. The greatest risk comes from dehydration in susceptible hosts.

Race

No racial predilection exists.

Sex

No sex predilection exists.

Age

In endemic countries, infections are much more common in children younger than 10-15 years (about 80% of infections). In this group, infections tend to be less frequent in infants younger than 12-18 months (see Table).

History

After exposure in nonimmune individuals, the incubation period is usually 1-11 days (mean, 7 d). The onset of illness may be abrupt in as many as 30% of cases. It may be preceded by a flulike illness. After a few days, acute symptoms subside and then may recur (61% of cases) in a waxing-waning pattern. Alternatively, a patient may experience persistent symptoms. The illness usually lasts 6-7 weeks but has been reported to persist for several months. The duration can be several months to a year in patients with HIV.

Physical

Vital signs are normal in most cases. Fever is unusual but, when present, is low grade. In the presence of moderate to severe dehydration, compensatory tachycardia, systolic blood pressure (SBP) less than 90 mm Hg, and decreased skin turgor may occur, and the patient may appear ill.

Causes

Risk of infection is secondary to the consumption of contaminated fruits, vegetables, water, or other foodstuffs (see Deterrence/Prevention for strategies that decrease the risk of acquiring this infection). The infectious inoculum is not known but is thought to be small.

Laboratory Studies

Histologic Findings

Duodenal and jejunal overall microscopic architecture is altered with mild to moderately severe villous atrophy (villous-to-crypt ratio reported 0.6-1.5:1 versus normal 3-4:1).

The above discussion of histology is adapted from Connor (1993[16] , 1999[17] ) and Ortega (1997[18] ).

Medical Care

Medical care includes oral or intravenous rehydration (appropriate to the degree of dehydration) and antibiotics. The antibiotic of choice for treating Cyclospora infection is TMP-SMZ.

Medication Summary

TMP-SMZ is the drug of choice. Immunocompetent patients become symptom-free within a median of 3 days. In a study of Haitian patients with AIDS, individuals cleared the organism on average 2.5 days into treatment during a 10-day regimen.

One small study of 20 patients with HIV compared TMP-SMZ (n = 9) with ciprofloxacin (n = 11) in the treatment of C cayetanensis infection.[19] With TMP-SMZ by day 7, diarrhea had ceased in 9 of 9 patients, and stools were negative for oocysts in all 9 patients. With ciprofloxacin by day 7, diarrhea ceased in 10 of 11 patients, and stools were negative for oocysts in 7 of 11 patients (64%). The conclusion was that, although ciprofloxacin is not as effective as TMP-SMZ, it is an acceptable alternative for patients unable to tolerate TMP-SMZ. However, this study has not been replicated, and other studies have commented that ciprofloxacin treatment did not produce a good response. The consensus among many practitioners is that ciprofloxacin is not a satisfactory treatment for cyclosporiasis, and they do not use it if the patient is allergic to sulfa.

Results from small studies have not demonstrated norfloxacin, metronidazole, tinidazole, quinacrine, and azithromycin to be effective.

Nitazoxanide, a 5-nitrothiazole derivative with broad-spectrum activity against helminths and protozoans, has been shown to be effective against C cayetanensis, with an efficacy 87% by the third dose (first, 71%; second 75%). Three percent of patients had minor side effects.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Clinical Context:  Combination antibiotic inhibits 2 sequential steps in bacterial folate synthesis. It has a wide spectrum of activity and reduced resistance because of the combined action of 2 drugs. Most gram-positive and gram-negative organisms are sensitive. Typically resistant organisms include Pseudomonas aeruginosa, Bacteroides fragilis, and enterococci. After oral administration, TMP peaks by 2 h and SMZ by 4 h. Respective half-lives are 11 h and 10 h.

Ciprofloxacin (Cipro)

Clinical Context:  Fluorinated 4-quinolone. Broad-spectrum antimicrobial inhibits gyrase-mediated DNA supercoiling in bacteria, leading to disruption of bacterial DNA replication. Effective against many gram-positive and gram-negative organisms. Inhibits several intracellular bacteria (ie, Chlamydia, Mycoplasma, Legionella, Brucella, Mycobacterium). In one study, 1 of 7 patients administered 500 mg 3 times qwk had a recurrence after 4 wk of therapy (no recurrences with TMP-SMZ). Well-absorbed after PO administration, peaks within 1-3 h, and serum elimination half-life is 5-6 h.

Class Summary

Therapy must be comprehensive, covering all likely pathogens in the context of this clinical setting.

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications

Deterrence/Prevention

Complications

Prognosis

Author

William H Shoff, MD, DTM&H, Director, PENN Travel Medicine; Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Jeffrey D Band, MD, Professor of Medicine, Oakland University William Beaumont School of Medicine; Director, Division of Infectious Diseases and International Medicine, Corporate Epidemiologist, William Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

John W King, MD, Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

Disclosure: MedScape Honoraria Other

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Amy J Behrman, MD Associate Professor, Department of Emergency Medicine, Director, Division of Occupational Medicine, University of Pennsylvania School of Medicine

Amy J Behrman, MD is a member of the following medical societies: American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM Associate Professor, Education Officer, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

References

  1. Shlim DR, Cohen MT, Eaton M, Rajah R, Long EG, Ungar BL. An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in Nepal. Am J Trop Med Hyg. Sep 1991;45(3):383-9. [View Abstract]
  2. Ortega YR, Sterling CR, Gilman RH, Cama VA, Díaz F. Cyclospora species--a new protozoan pathogen of humans. N Engl J Med. May 6 1993;328(18):1308-12. [View Abstract]
  3. Centers for Disease Control and Prevention. Update: outbreaks of Cyclospora cayetanensis infection--United States and Canada, 1996. MMWR Morb Mortal Wkly Rep. Jul 19 1996;45(28):611-2. [View Abstract]
  4. Pape JW, Verdier RI, Boncy M, Boncy J, Johnson WD Jr. Cyclospora infection in adults infected with HIV. Clinical manifestations, treatment, and prophylaxis. Ann Intern Med. Nov 1 1994;121(9):654-7. [View Abstract]
  5. Galván A, Magnet A, Izquierdo F, Fenoy S, Rueda C, Fernández Vadillo C, et al. Molecular characterization of human pathogenic microsporidia and Cyclospora cayetanensis in different water sources from Spain: a year-long longitudinal study. Appl Environ Microbiol. Nov 2 2012;[View Abstract]
  6. Ben Ayed L, Yang W, Widmer G, Cama V, Ortega Y, Xiao L. Survey and genetic characterization of wastewater in Tunisia for Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi, Cyclospora cayetanensis and Eimeria spp. J Water Health. Sep 2012;10(3):431-44. [View Abstract]
  7. Kitajima M, Haramoto E, Iker BC, Gerba CP. Occurrence of Cryptosporidium, Giardia, and Cyclospora in influent and effluent water at wastewater treatment plants in Arizona. Sci Total Environ. Jun 15 2014;484:129-36. [View Abstract]
  8. Hall RL, Jones JL, Hurd S, Smith G, Mahon BE, Herwaldt BL. Population-based active surveillance for Cyclospora infection--United States, Foodborne Diseases Active Surveillance Network (FoodNet), 1997-2009. Clin Infect Dis. Jun 2012;54 Suppl 5:S411-7. [View Abstract]
  9. Baldursson S, Karanis P. Waterborne transmission of protozoan parasites: review of worldwide outbreaks - an update 2004-2010. Water Res. Dec 15 2011;45(20):6603-14. [View Abstract]
  10. Orozco-Mosqueda GE, Martínez-Loya OA, Ortega YR. Cyclospora cayetanensis in a Pediatric Hospital in Morelia, México. Am J Trop Med Hyg. Sep 3 2014;91(3):537-40. [View Abstract]
  11. Thima K, Mori H, Praevanit R, Mongkhonmu S, Waikagul J, Watthanakulpanich D. Recovery of Cyclospora cayetanensis among asymptomatic rural Thai schoolchildren. Asian Pac J Trop Med. Feb 2014;7(2):119-23. [View Abstract]
  12. Liu H, Shen Y, Yin J, Yuan Z, Jiang Y, Xu Y, et al. Prevalence and genetic characterization of Cryptosporidium, Enterocytozoon, Giardia and Cyclospora in diarrheal outpatients in China. BMC Infect Dis. Jan 13 2014;14:25. [View Abstract]
  13. Sánchez-Vega JT, Cabrera-Fuentes HA, Romero-Olmedo AJ, Ortiz-Frías JL, Sokolina F, Barreto G. Cyclospora cayetanensis: this emerging protozoan pathogen in Mexico. Am J Trop Med Hyg. Feb 2014;90(2):351-3. [View Abstract]
  14. Parija SC, Shivaprakash MR, Jayakeerthi SR. Evaluation of lacto-phenol cotton blue (LPCB) for detection of Cryptosporidium, Cyclospora and Isospora in the wet mount preparation of stool. Acta Trop. Mar 2003;85(3):349-54. [View Abstract]
  15. Parija SC, Prabhakar PK. Evaluation of lacto-phenol cotton blue for wet mount preparation of feces. J Clin Microbiol. Apr 1995;33(4):1019-21. [View Abstract]
  16. Connor BA, Shlim DR, Scholes JV, Rayburn JL, Reidy J, Rajah R. Pathologic changes in the small bowel in nine patients with diarrhea associated with a coccidia-like body. Ann Intern Med. Sep 1 1993;119(5):377-82. [View Abstract]
  17. Connor BA, Reidy J, Soave R. Cyclosporiasis: clinical and histopathologic correlates. Clin Infect Dis. Jun 1999;28(6):1216-22. [View Abstract]
  18. Ortega YR, Nagle R, Gilman RH, et al. Pathologic and clinical findings in patients with cyclosporiasis and a description of intracellular parasite life-cycle stages. J Infect Dis. Dec 1997;176(6):1584-9. [View Abstract]
  19. Verdier RI, Fitzgerald DW, Johnson WD Jr, Pape JW. Trimethoprim-sulfamethoxazole compared with ciprofloxacin for treatment and prophylaxis of Isospora belli and Cyclospora cayetanensis infection in HIV-infected patients. A randomized, controlled trial. Ann Intern Med. Jun 6 2000;132(11):885-8. [View Abstract]
  20. Chandra V, Torres M, Ortega YR. Efficacy of Wash Solutions in Recovering Cyclospora cayetanensis, Cryptosporidium parvum, and Toxoplasma gondii from Basil. J Food Prot. Aug 2014;77(8):1348-54. [View Abstract]
  21. Al-Braiken FA, Amin A, Beeching NJ, Hommel M, Hart CA. Detection of Cryptosporidium amongst diarrhoeic and asymptomatic children in Jeddah, Saudi Arabia. Ann Trop Med Parasitol. Jul 2003;97(5):505-10. [View Abstract]
  22. Alfano-Sobsey EM, Eberhard ML, Seed JR, Weber DJ, Won KY, Nace EK. Human challenge pilot study with Cyclospora cayetanensis. Emerg Infect Dis. Apr 2004;10(4):726-8. [View Abstract]
  23. Arora DR, Arora B. AIDS-associated parasitic diarrhoea. Indian J Med Microbiol. Jul-Sep 2009;27(3):185-90. [View Abstract]
  24. Arrowood MJ, Hurd MR, Mead JR. A new method for evaluating experimental cryptosporidial parasite loads using immunofluorescent flow cytometry. J Parasitol. Jun 1995;81(3):404-9. [View Abstract]
  25. Ashford RW. Occurrence of an undescribed coccidian in man in Papua New Guinea. Ann Trop Med Parasitol. Oct 1979;73(5):497-500. [View Abstract]
  26. Ashton CH. Solvent abuse. BMJ. Jan 20 1990;300(6718):135-6. [View Abstract]
  27. Bern C, Arrowood MJ, Eberhard M, Maguire JH. Cyclospora in Guatemala: further considerations. J Clin Microbiol. Feb 2002;40(2):731-2. [View Abstract]
  28. Bern C, Hernandez B, Lopez MB, et al. Epidemiologic studies of Cyclospora cayetanensis in Guatemala. Emerg Infect Dis. Nov-Dec 1999;5(6):766-74. [View Abstract]
  29. Bern C, Ortega Y, Checkley W, et al. Epidemiologic differences between cyclosporiasis and cryptosporidiosis in Peruvian children. Emerg Infect Dis. Jun 2002;8(6):581-5. [View Abstract]
  30. Betancourt WQ, Rose JB. Drinking water treatment processes for removal of Cryptosporidium and Giardia. Vet Parasitol. Dec 9 2004;126(1-2):219-34. [View Abstract]
  31. Brennan MK, MacPherson DW, Palmer J, Keystone JS. Cyclosporiasis: a new cause of diarrhea. CMAJ. Nov 1 1996;155(9):1293-6. [View Abstract]
  32. Cama RI, Parashar UD, Taylor DN, et al. Enteropathogens and other factors associated with severe disease in children with acute watery diarrhea in Lima, Peru. J Infect Dis. May 1999;179(5):1139-44. [View Abstract]
  33. Centers for Disease Control and Prevention. Cyclospora infection: information for health care providers. CDC Website.
  34. Centers for Disease Control and Prevention. Other CDC information on Cyclospora.
  35. Centers for Disease Control and Prevention. Outbreak of cyclosporiasis--northern Virginia-Washington, D.C.-Baltimore, Maryland, metropolitan area, 1997. MMWR Morb Mortal Wkly Rep. Aug 1 1997;46(30):689-91. [View Abstract]
  36. Centers for Disease Control and Prevention. Outbreak of cyclosporiasis--Ontario, Canada, May 1998. MMWR Morb Mortal Wkly Rep. Oct 2 1998;47(38):806-9. [View Abstract]
  37. Centers for Disease Control and Prevention. Parasites and health: Cyclosporiasis. CDC Website.
  38. Chacin-Bonilla L, Mejia de Young M, Estevez J. Prevalence and pathogenic role of Cyclospora cayetanensis in a Venezuelan community. Am J Trop Med Hyg. Mar 2003;68(3):304-6. [View Abstract]
  39. Chacín-Bonilla L. Transmission of Cyclospora cayetanensis infection: a review focusing on soil-borne cyclosporiasis. Trans R Soc Trop Med Hyg. Mar 2008;102(3):215-6. [View Abstract]
  40. Cole DJ, Snowden K, Cohen ND, Smith R. Detection of Cryptosporidium parvum in horses: thresholds of acid-fast stain, immunofluorescence assay, and flow cytometry. J Clin Microbiol. Feb 1999;37(2):457-60. [View Abstract]
  41. Connor BA, Johnson EJ, Soave R. Reiter syndrome following protracted symptoms of Cyclospora infection. Emerg Infect Dis. May-Jun 2001;7(3):453-4. [View Abstract]
  42. Connor BA, Shlim DR. Cyclosporiasis. In: Strickland, ed. Hunter's Tropical Diseases and Emerging Infections. 9th ed. Philadelphia, PA: WB Saunders Co; 2000:600-3.
  43. Cunha BA. Antibiotic Essentials. 5th ed. Royal Oak, Mich: Physicians Press; 2006.
  44. Dalton C, Goater AD, Burt JP, Smith HV. Analysis of parasites by electrorotation. J Appl Microbiol. 2004;96(1):24-32. [View Abstract]
  45. Dawson D. Foodborne protozoan parasites. Int J Food Microbiol. Aug 25 2005;103(2):207-27. [View Abstract]
  46. Di Gliullo AB, Cribari MS, Bava AJ, Cicconetti JS, Collazos R. Cyclospora cayetanensis in sputum and stool samples. Rev Inst Med Trop Sao Paulo. Mar-Apr 2000;42(2):115-7. [View Abstract]
  47. Diaz E, Mondragon J, Ramirez E, Bernal R. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg. Apr 2003;68(4):384-5. [View Abstract]
  48. Dixon BR, Bussey JM, Parrington LJ, Parenteau M. Detection of Cyclospora cayetanensis oocysts in human fecal specimens by flow cytometry. J Clin Microbiol. May 2005;43(5):2375-9. [View Abstract]
  49. Dixon BR, Parenteau M, Martineau C, Fournier J. A comparison of conventional microscopy, immunofluorescence microscopy and flow cytometry in the detection of Giardia lamblia cysts in beaver fecal samples. J Immunol Methods. Mar 10 1997;202(1):27-33. [View Abstract]
  50. Doller PC, Dietrich K, Filipp N, et al. Cyclosporiasis outbreak in Germany associated with the consumption of salad. Emerg Infect Dis. Sep 2002;8(9):992-4. [View Abstract]
  51. Dorny P, Praet N, Deckers N, Gabriel S. Emerging food-borne parasites. Vet Parasitol. Aug 7 2009;163(3):196-206. [View Abstract]
  52. Eberhard ML, Nace EK, Freeman AR, Streit TG, da Silva AJ, Lammie PJ. Cyclospora cayetanensis infections in Haiti: a common occurrence in the absence of watery diarrhea. Am J Trop Med Hyg. Apr 1999;60(4):584-6. [View Abstract]
  53. Fleming CA, Caron D, Gunn JE, Barry MA. A foodborne outbreak of Cyclospora cayetanensis at a wedding: clinical features and risk factors for illness. Arch Intern Med. May 25 1998;158(10):1121-5. [View Abstract]
  54. Goodgame RW. Understanding intestinal spore-forming protozoa: cryptosporidia, microsporidia, isospora, and cyclospora. Ann Intern Med. Feb 15 1996;124(4):429-41. [View Abstract]
  55. Graczyk TK, Ortega YR, Conn DB. Recovery of waterborne oocysts of Cyclospora cayetanensis by Asian freshwater clams (Corbicula fluminea). Am J Trop Med Hyg. Dec 1998;59(6):928-32. [View Abstract]
  56. Hamazoe R, Maeta M, Matsui T, Shibata S, Shiota S, Kaibara N. CA72-4 compared with carcinoembryonic antigen as a tumour marker for gastric cancer. Eur J Cancer. 1992;28A(8-9):1351-4. [View Abstract]
  57. Hart AS, Ridinger MT, Soundarajan R, Peters CS, Swiatlo AL, Kocka FE. Novel organism associated with chronic diarrhoea in AIDS. Lancet. Jan 20 1990;335(8682):169-70. [View Abstract]
  58. Herwaldt BL. Cyclospora cayetanensis: a review, focusing on the outbreaks of cyclosporiasis in the 1990s. Clin Infect Dis. Oct 2000;31(4):1040-57. [View Abstract]
  59. Herwaldt BL, Ackers ML. An outbreak in 1996 of cyclosporiasis associated with imported raspberries. The Cyclospora Working Group. N Engl J Med. May 29 1997;336(22):1548-56. [View Abstract]
  60. Herwaldt BL, Beach MJ. The return of Cyclospora in 1997: another outbreak of cyclosporiasis in North America associated with imported raspberries. Cyclospora Working Group. Ann Intern Med. Feb 2 1999;130(3):210-20. [View Abstract]
  61. Ho AY, Lopez AS, Eberhart MG, et al. Outbreak of cyclosporiasis associated with imported raspberries, Philadelphia, Pennsylvania, 2000. Emerg Infect Dis. Aug 2002;8(8):783-8. [View Abstract]
  62. Hoge CW, Echeverria P, Rajah R, et al. Prevalence of Cyclospora species and other enteric pathogens among children less than 5 years of age in Nepal. J Clin Microbiol. Nov 1995;33(11):3058-60. [View Abstract]
  63. Hoge CW, Shlim DR, Echeverria P. Cyanobacterium-like cyclospora species. N Engl J Med. Nov 11 1993;329(20):1504-5. [View Abstract]
  64. Hoge CW, Shlim DR, Ghimire M, et al. Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and foreign residents in Nepal. Lancet. Mar 18 1995;345(8951):691-3. [View Abstract]
  65. Hoge CW, Shlim DR, Rajah R, et al. Epidemiology of diarrhoeal illness associated with coccidian-like organism among travellers and foreign residents in Nepal. Lancet. May 8 1993;341(8854):1175-9. [View Abstract]
  66. Huang P, Weber JT, Sosin DM, et al. The first reported outbreak of diarrheal illness associated with Cyclospora in the United States. Ann Intern Med. Sep 15 1995;123(6):409-14. [View Abstract]
  67. Hussein EM, Abdul-Manaem AH, el-Attary SL. Cyclospora cayetanensis oocysts in sputum of a patient with active pulmonary tuberculosis, case report in Ismailia, Egypt. J Egypt Soc Parasitol. Dec 2005;35(3):787-93. [View Abstract]
  68. Jelinek T, Lotze M, Eichenlaub S, Löscher T, Nothdurft HD. Prevalence of infection with Cryptosporidium parvum and Cyclospora cayetanensis among international travellers. Gut. Dec 1997;41(6):801-4. [View Abstract]
  69. Kansouzidou A, Charitidou C, Varnis T, Vavatsi N, Kamaria F. Cyclospora cayetanensis in a patient with travelers' diarrhea: case report and review. J Travel Med. Jan-Feb 2004;11(1):61-3. [View Abstract]
  70. Karanja RM, Gatei W, Wamae N. Cyclosporiasis: an emerging public health concern around the world and in Africa. Afr Health Sci. Jun 2007;7(2):62-7. [View Abstract]
  71. Kimura K, Kumar Rai S, Takemasa K, Ishibashi Y, Kawabata M, Belosevic M. Comparison of three microscopic techniques for diagnosis of Cyclospora cayetanensis. FEMS Microbiol Lett. Sep 1 2004;238(1):263-6. [View Abstract]
  72. Long EG, Ebrahimzadeh A, White EH, Swisher B, Callaway CS. Alga associated with diarrhea in patients with acquired immunodeficiency syndrome and in travelers. J Clin Microbiol. Jun 1990;28(6):1101-4. [View Abstract]
  73. Long EG, White EH, Carmichael WW, et al. Morphologic and staining characteristics of a cyanobacterium-like organism associated with diarrhea. J Infect Dis. Jul 1991;164(1):199-202. [View Abstract]
  74. Lopez AS, Bendik JM, Alliance JY, et al. Epidemiology of Cyclospora cayetanensis and other intestinal parasites in a community in Haiti. J Clin Microbiol. May 2003;41(5):2047-54. [View Abstract]
  75. Mandell GL, Sande MA. Sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. In: Goodman LS, Limbird LE, Milinoff PB, et al, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: Pergamon Press; 1996:1057-72.
  76. Mansfield LS, Gajadhar AA. Cyclospora cayetanensis, a food- and waterborne coccidian parasite. Vet Parasitol. Dec 9 2004;126(1-2):73-90. [View Abstract]
  77. Mead PS, Slutsker L, Dietz V, et al. Food-related illness and death in the United States. Emerg Infect Dis. Sep-Oct 1999;5(5):607-25. [View Abstract]
  78. Miegeville M, Koubi V, Dan LC, Barbier JP, Cam PD. [Cyclospora cayetanensis presence in aquatic surroundings in Hanoi (Vietnam). Environmental study (well water, lakes and rivers)]. Bull Soc Pathol Exot. Aug 2003;96(3):149-52. [View Abstract]
  79. Mota P, Rauch CA, Edberg SC. Microsporidia and Cyclospora: epidemiology and assessment of risk from the environment. Crit Rev Microbiol. 2000;26(2):69-90. [View Abstract]
  80. Naranjo J, Sterling CR, Gilman R. Cryptosporidium muris-like objects from fecal samples of Peruvians. Abstract, 38th Annual Meeting of ASTMH. December 10-14, 1989.
  81. Nhieu JT, Nin F, Fleury-Feith J, Chaumette MT, Schaeffer A, Bretagne S. Identification of intracellular stages of Cyclospora species by light microscopy of thick sections using hematoxylin. Hum Pathol. Oct 1996;27(10):1107-9. [View Abstract]
  82. Nimri LF. Cyclospora cayetanensis and other intestinal parasites associated with diarrhea in a rural area of Jordan. Int Microbiol. Jun 2003;6(2):131-5. [View Abstract]
  83. Nunez FA, Gonzalez OM, Gonzalez I, Escobedo AA, Cordoví RA. Intestinal coccidia in Cuban pediatric patients with diarrhea. Mem Inst Oswaldo Cruz. Jun 2003;98(4):539-42. [View Abstract]
  84. Ooi WW, Zimmerman SK, Needham CA. Cyclospora species as a gastrointestinal pathogen in immunocompetent hosts. J Clin Microbiol. May 1995;33(5):1267-9. [View Abstract]
  85. Orlandi PA, Carter L, Brinker AM, et al. Targeting single-nucleotide polymorphisms in the 18S rRNA gene to differentiate Cyclospora species from Eimeria species by multiplex PCR. Appl Environ Microbiol. Aug 2003;69(8):4806-13. [View Abstract]
  86. Orlandi PA, Lampel KA. Extraction-free, filter-based template preparation for rapid and sensitive PCR detection of pathogenic parasitic protozoa. J Clin Microbiol. Jun 2000;38(6):2271-7. [View Abstract]
  87. Osterholm MT. Cyclosporiasis and raspberries--lessons for the future. N Engl J Med. May 29 1997;336(22):1597-9. [View Abstract]
  88. Physicians Desk Reference. Montvale, NJ: Thomson Medical Economics; 2001.
  89. Pinge-Suttor V, Douglas C, Wettstein A. Cyclospora infection masquerading as coeliac disease. Med J Aust. Mar 15 2004;180(6):295-6. [View Abstract]
  90. Popovici I, Dahorea C, Rugina A, Coman G. [Acute diarrhea associated with Cyclospora cayetanensis]. Rev Med Chir Soc Med Nat Iasi. Oct-Dec 2003;107(4):877-80. [View Abstract]
  91. Pratdesaba RA, Gonzalez M, Piedrasanta E, et al. Cyclospora cayetanensis in three populations at risk in Guatemala. J Clin Microbiol. Aug 2001;39(8):2951-3. [View Abstract]
  92. Quintero-Betancourt W, Peele ER, Rose JB. Cryptosporidium parvum and Cyclospora cayetanensis: a review of laboratory methods for detection of these waterborne parasites. J Microbiol Methods. May 2002;49(3):209-24. [View Abstract]
  93. Rabold JG, Hoge CW, Shlim DR, Kefford C, Rajah R, Echeverria P. Cyclospora outbreak associated with chlorinated drinking water. Lancet. Nov 12 1994;344(8933):1360-1. [View Abstract]
  94. Ribes JA, Seabolt JP, Overman SB. Point prevalence of Cryptosporidium, Cyclospora, and Isospora infections in patients being evaluated for diarrhea. Am J Clin Pathol. Jul 2004;122(1):28-32. [View Abstract]
  95. Richardson RF Jr, Remler BF, Katirji B, Murad MH. Guillain-Barre syndrome after Cyclospora infection. Muscle Nerve. May 1998;21(5):669-71. [View Abstract]
  96. Shields JM, Olson BH. Cyclospora cayetanensis: a review of an emerging parasitic coccidian. Int J Parasitol. Apr 2003;33(4):371-91. [View Abstract]
  97. Shields JM, Olson BH. PCR-restriction fragment length polymorphism method for detection of Cyclospora cayetanensis in environmental waters without microscopic confirmation. Appl Environ Microbiol. Aug 2003;69(8):4662-9. [View Abstract]
  98. Shlim DR. Cyclospora cayetanesis. Clin Lab Med. Dec 2002;22(4):927-36. [View Abstract]
  99. Sifuentes-Osornio J, Porras-Cortes G, Bendall RP, Morales-Villarreal F, Reyes-Teran G, Ruiz-Palacios GM. Cyclospora cayetanensis infection in patients with and without AIDS: biliary disease as another clinical manifestation. Clin Infect Dis. Nov 1995;21(5):1092-7. [View Abstract]
  100. Soave R. Cyclospora: an overview. Clin Infect Dis. Sep 1996;23(3):429-35; quiz 436-7. [View Abstract]
  101. Steele M, Unger S, Odumeru J. Sensitivity of PCR detection of Cyclospora cayetanensis in raspberries, basil, and mesclun lettuce. J Microbiol Methods. Aug 2003;54(2):277-80. [View Abstract]
  102. Steiner TS, Pape JW, Guerrant RL. Intestinal coccidial infections. In: Guerrant RL, et al, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. Philadelphia, Pa: Churchill Livingstone; 1999:721-35.
  103. Sterling CR, Ortega YR. Cyclospora: an enigma worth unraveling. Emerg Infect Dis. Jan-Feb 1999;5(1):48-53. [View Abstract]
  104. Sturbaum GD, Ortega YR, Gilman RH, Sterling CR, Cabrera L, Klein DA. Detection of Cyclospora cayetanensis in wastewater. Appl Environ Microbiol. Jun 1998;64(6):2284-6. [View Abstract]
  105. Taylor DN, Houston R, Shlim DR, Bhaibulaya M, Ungar BL, Echeverria P. Etiology of diarrhea among travelers and foreign residents in Nepal. JAMA. Sep 2 1988;260(9):1245-8. [View Abstract]
  106. Varma M, Hester JD, Schaefer FW 3rd, Ware MW, Lindquist HD. Detection of Cyclospora cayetanensis using a quantitative real-time PCR assay. J Microbiol Methods. Apr 2003;53(1):27-36. [View Abstract]
  107. Verweij JJ, Laeijendecker D, Brienen EA, van Lieshout L, Polderman AM. Detection of Cyclospora cayetanensis in travellers returning from the tropics and subtropics using microscopy and real-time PCR. Int J Med Microbiol. Jun 2003;293(2-3):199-202. [View Abstract]
  108. Visvesvara GS, Moura H, Kovacs-Nace E, Wallace S, Eberhard ML. Uniform staining of Cyclospora oocysts in fecal smears by a modified safranin technique with microwave heating. J Clin Microbiol. Mar 1997;35(3):730-3. [View Abstract]
  109. Wang KX, Li CP, Wang J, Tian Y. Cyclospore cayetanensis in Anhui, China. World J Gastroenterol. Dec 2002;8(6):1144-8. [View Abstract]
  110. Wiesner J, Reichenberg A, Heinrich S, Schlitzer M, Jomaa H. The plastid-like organelle of apicomplexan parasites as drug target. Curr Pharm Des. 2008;14(9):855-71. [View Abstract]
  111. Yazar S, Yalcln S, Sahin I. Human cyclosporiosis in Turkey. World J Gastroenterol. Jun 15 2004;10(12):1844-7. [View Abstract]
  112. Yu JR, Sohn WM. A case of human cyclosporiasis causing traveler's diarrhea after visiting Indonesia. J Korean Med Sci. Oct 2003;18(5):738-41. [View Abstract]
  113. Zar FA, El-Bayoumi E, Yungbluth MM. Histologic proof of acalculous cholecystitis due to Cyclospora cayetanensis. Clin Infect Dis. Dec 15 2001;33(12):E140-1. [View Abstract]
Pattern of Spread Countries Comments
EndemicBangladesh, Brazil, Chile, China, Cuba, Dominican Republic, Egypt, Guatemala, Haiti, India, Indonesia, Jordan, Mexico, Morocco, Nepal, Nigeria, Pakistan, Peru, Puerto Rico, Romania, Saudi Arabia, Tanzania, Thailand, Turkey, Venezuela, Viet Nam, Zimbabwe Prevalence (1-15%†) varies significantly with the season and from year to year; children (≤ 9 y, most studies) account for 70-80% cases, which are typically asymptomatic (72-94%); asymptomatic disease is higher in older children (10-18 y) and adults (>18 y); infection rate in those with HIV is significantly higher than overall prevalence
International travel-relatedAustralia, Belgium, Czech Republic, Germany, Greece, Ireland, Italy, Japan, The Netherlands, Spain, Switzerland, United Kingdom, United States ≤4% returning travelers with diarrhea
Foodborne outbreaksCanada, United States, Germany, MexicoCanada/United States: raspberries, blackberries, mesclun, basil‡; Germany: lettuce imported from Southern France/Southern Italy; Mexico: watercress
Waterborne outbreaksUnited States (Chicago), Nepal14 cases of cyclosporiasis; tap water in medical dormitory, suspected source was contaminated water storage tank; 12 of 14 developed cyclosporiasis
* Community-based studies

† Highest in spring and early summer

‡ Fresh produce. Raspberries from Guatemala; blackberries from Guatemala or undetermined source; mesclun (young salad greens, eg, spring mix, field greens, baby greens, gourmet salad mix) from Peru or United States; basin from Mexico or United States