MICROBIOLOGY

• Single-celled coccidian parasite
• Member of family Eimeriidae, subclass Coccidiasina, subphylum Apicomplexa.
  • Cyclospora cayetanensis is considered a human-specific parasite; no confirmed animal reservoir has been identified.
  • Infected persons shed unsporulated (non-infective) oocysts in feces [life cycle].
    • Under favorable environmental conditions, oöcysts generally require days to approximately 1–2 weeks after excretion to sporulate and become infectious; therefore, direct person-to-person transmission is unlikely.
  • Other members of Cyclospora are found in animals, including rodents and vipers.
  • Oocysts are spherical, 7.7–9.9 μm in diameter, and may contain granular or morula-like internal material [Fig 1].
    • Variably acid-fast and characteristically autofluoresce blue-green under ultraviolet microscopy.
• It can be responsible for water- or food-borne outbreaks.
• Oöcysts are relatively resistant to chlorine and to many routine produce-washing or water-sanitizing procedures.

CLINICAL

• Diarrheal illness is found worldwide but is more common in tropical and subtropical settings; transmission occurs through ingestion of food or water contaminated with sporulated oocysts; contamination of produce and agricultural water has been documented.
  • Typical onset is ~ 1 week after exposure, although it may range from 2 to 14 days.
    • Often remitting and relapsing for weeks to months, ultimately self-limiting.
    • Include cyclosporiasis as a consideration in persistent or relapsing watery diarrhea, particularly after travel to tropical or subtropical regions, during spring or summer outbreaks, after fresh-produce exposure, or in an immunocompromised host.
  • Associated with fresh-food-related outbreaks in the U.S.
    • U.S. outbreaks have been associated with leafy greens, herbs, berries, vegetable trays, and other fresh produce, including both imported and domestically grown products.
    • In recent years, Cyclospora is probably more commonly seen in clinical practice as domestic- rather than travel-acquired. Largest reported outbreak in U.S. history 2026 (ongoing at time of this module’s update):
      • • Multi-state outbreak linked to shredded lettuce served at Taco Bell restaurants alongside a separate, emerging cluster of unknown source.
          • 1947 cases resulting in 98 hospitalizations to date but no reported deaths (as of 7/24/26, see CDC page for updates) related to the shredded iceberg lettuce. Nine states to date (Illinois, Indiana, Kansas, Kentucky, Michigan, Ohio, Oklahoma, Pennsylvania, and West Virginia) with onset in late June 2026.
          • National totals are higher (>4100 lab-confirmed cases) since May 1, 2026, in 47 states.
    • Majority of cases in North America occur in May-August.
  • Waterborne outbreaks have also been reported, particularly in endemic, resource-limited settings such as Nepal.
• After an incubation period averaging approximately 1 week, patients typically develop watery diarrhea, anorexia, abdominal cramping, bloating, nausea, weight loss, and prominent fatigue.
  
  • Fever is uncommon and usually low grade; grossly bloody or overtly inflammatory diarrhea is unusual, and peripheral eosinophilia is not characteristic.
    • Myalgia and vomiting are uncommon.
  • Host immune status helps determine if the disease is more severe.
    • In AIDS or advanced immunosuppression, symptoms are generally more severe and can range from asymptomatic to severe; ascending biliary tract infection has been rarely reported.
    • Prevalence among persons with HIV varies markedly by geographic region and degree of immunosuppression.
• Diagnosis: Testing for Cyclospora is not included in every routine ova-and-parasite examination or gastrointestinal molecular panel; clinicians should confirm that the ordered test specifically includes C. cayetanensis.
  
  • Direct exam of stool (phase contrast or bright field microscopy), concentrated specimens preferred.
    • Oöcysts are 8-10 um in size (Figure 2), variably acid-fast using modified Ziehl-Neelsen.
    • Safranin stain (hot safranin is even better if available) and auto-fluorescence under UV improve sensitivity.
      • Note: Giemsa, trichrome, and Gram-chromotrope stains are unreliable in detecting Cyclospora oöcysts.
    • Additional key points: regarding staining from DPDx (CDC) and sporulation assay (done to distinguish from blue-green algae, now less commonly performed).
    • Because oocyst shedding may be intermittent and low-level, a single negative direct stool specimen for microscopy does not exclude infection; collection of three specimens on separate days may improve sensitivity when clinical suspicion remains high.
  • NAAT is generally more sensitive than conventional microscopy, although performance depends on the assay, organism burden, specimen processing, and comparator method.
    
    • Many commercially available multiplex GI panels do not include Cyclospora.
      • Exceptions (FDA-cleared multiplex panels): some institutions may have in-house assays.
        • Biofire FilmArray™ Gastrointestinal Panel
          • An analytic study estimated a limit of detection of approximately 20 oocysts per 200 μL of stool; detection was inconsistent at lower concentrations[7].
        • QIAstat Gastrointestinal Panel 2
          
          • A 2025 multicenter evaluation of the QIAstat-Dx GI Panel 2 reported positive percent agreement of at least 95% for C. cayetanensis[5].
• Note: organisms may be missed on a routine exam or mistaken for Cryptosporidium.
  • Cyclospora may be confused with Cryptosporidium, but Cyclospora oocysts are larger—approximately 8–10 μm versus 4–6 μm—and characteristically autofluoresce.
  • Confirm that the local assay includes Cyclospora; if not, request a Cyclospora-specific NAAT or microscopy using modified acid-fast staining and/or UV autofluorescence, which may require referral to a public health or reference laboratory.

SITES OF INFECTION

• GI:
  • Small intestine: primary site of infection, with villous injury and mucosal inflammation.
  • Biliary tract (rare, seen in patients with advanced immunosuppression)
  • Gallbladder (rare, seen in patients with advanced immunosuppression)
• Systemic:
  • Rare postinfectious reactive-arthritis–like manifestations have been described in isolated case reports.

TREATMENT

OTHER INFORMATION

• Cyclosporiasis is a nationally notifiable disease and is reportable in 47 states, the District of Columbia, and New York City.
  
  • Molecular testing may account for increased recognition of this infection compared to traditional stool analysis.
  • U.S. outbreaks continue to occur in association with both imported and domestically grown fresh produce.
• Prevention depends on preventing fecal contamination of produce and agricultural water, improving sanitation throughout production and distribution, and avoiding unsafe food and water during travel.
  
  • Oöcysts are resistant to chlorine concentrations typically used for routine water treatment and produce washing.
  • FDA Bacterial Analytical Manual Chapters 19b and 19c describe validated molecular methods for detecting C. cayetanensis in fresh produce and agricultural water.
• Cyclosporiasis is an important cause of persistent diarrhea in travelers returning from tropical and subtropical regions, including parts of Latin America, the Caribbean, South and Southeast Asia, and other endemic areas.

Basis for recommendation

1. Li J, Cui Z, Qi M, et al. Advances in Cyclosporiasis Diagnosis and Therapeutic Intervention. Front Cell Infect Microbiol. 2020;10:43.  [PMID:32117814]

   Comment: Narrative review of the epi, diagnostic tools, and treatment of Cyclospora cayetanensis.
   

2. Giangaspero A, Gasser RB. Human cyclosporiasis. Lancet Infect Dis. 2019;19(7):e226-e236.  [PMID:30885589]

   Comment: There is little good epidemiology to understand the global extent of this infectious disease, but the authors believe it is likely underestimated. The review article provides foundational opinions on diagnosis and management.
   

3. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017;65(12):e45-e80.  [PMID:29053792]

   Comment: The guideline includes items regarding Cyclospora. There is limited data regarding therapeutics in the literature.
   

References

4. Mahdavi F, Pouryousef A, Mohammadi MR, et al. Worldwide Epidemiology of Cyclospora cayetanensis in HIV/AIDS Patients: A Systematic Review and Meta-Analysis. Acta Parasitol. 2025;70(4):163.  [PMID:40690092]

   Comment: Review of 73 studies revealed an approximate prevalence of 4% among people living with HIV/AIDS.
   

5. Szymczak WA, Engsbro AL, Lisby JG, et al. Multicenter evaluation of the QIAstat-Dx Gastrointestinal Panel 2, a multiplex PCR platform for the diagnosis of acute gastroenteritis. J Clin Microbiol. 2025;63(8):e0198324.  [PMID:40643259]

   Comment: In the overall clinical-specimen analysis, the panel demonstrated 95.8% positive percent agreement and 100% negative percent agreement for C. cayetanensis, although the number of positive specimens was limited.
   

6. Chen Y, Qin Z, Li J, et al. The global prevalence of Cyclospora cayetanensis infection: A systematic review, meta-analysis, and meta-regression. Acta Trop. 2024;253:107175.  [PMID:38492874]

   Comment: Global epidemiology overview that speaks to the potential impact of climatic factors and other influences such as food and water.
   

7. Peterson A, Richins T, Houghton K, et al. The limit of detection of the BioFire® FilmArray® gastrointestinal panel for the foodborne parasite Cyclospora cayetanensis. Diagn Microbiol Infect Dis. 2023;107(2):116030.  [PMID:37572510]

   Comment: This GI panel found the FilmArray GI panel detected samples with ≥20 C. cayetanensis oocysts in 100% of replicates, with varying detection among samples with 1, 5, or 10 C. cayetanensis oöcysts.
   

8. Sarfo FS, Dompreh A, Asibey SO, et al. The Clinical Features and Immunological Signature of Cyclospora cayetanensis Co-Infection among People Living with HIV in Ghana. Microorganisms. 2022;10(7).  [PMID:35889126]

   Comment: This was a cross-sectional study evaluating >600 individuals with HIV in Ghana. C. cayetanensis was found in 8.7% of HIV pos patients (vs 1.3% of HIV-negative) or 14% among those with CD4 counts< 200.
   Rating: Important
   

9. Bateman AC, Kim YJ, Guaracao AI, et al. Performance and Impact of the BioFire FilmArray Gastrointestinal Panel on a Large Cyclospora Outbreak in Wisconsin, 2018. J Clin Microbiol. 2020;58(2).  [PMID:31801836]

   Comment: This letter concerns testing during the largest known outbreak in the US. In Wisconsin, 177 cases were linked to consuming prepackaged mixed vegetable trays containing broccoli, cauliflower, carrots, and dill dip. Of the FilmArray GI-positive specimens, 94/99 (95%) were confirmed as positive by autofluorescence at WSLH. This was consistent with the confirmation rate of laboratory specimens that used modified acid-fast staining (24/26 [92%]). The high confirmation rate by autofluorescence microscopy demonstrates the reliability of FilmArray GI Cyclospora-positive results with a large number of real-world clinical specimens [the number of FilmArray GI-positive specimens in this outbreak (99 specimens) is more than 5 times higher than the number of positive specimens in the FDA 510(k) clearance data (19 specimens).
   

10. Tack DM, Marder EP, Griffin PM, et al. Preliminary Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2015-2018. MMWR Morb Mortal Wkly Rep. 2019;68(16):369-373.  [PMID:31022166]

    Comment: Cyclospora has been more commonly identified in 2015-17 due to outbreaks associated with imported produce.
    

11. Kaminsky RG, Lagos J, Raudales Santos G, et al. Marked seasonality of Cyclospora cayetanensis infections: ten-year observation of hospital cases, Honduras. BMC Infect Dis. 2016;16:66.  [PMID:26847438]

    Comment: A study of 35,157 fecal samples found cases of Cyclospora only from residents of urban areas with a striking seasonality. Of the 125 C. cayetanensis infections, 83.3% were identified during the rainy months of May to August.
    

12. Guo Y, Roellig DM, Li N, et al. Multilocus Sequence Typing Tool for Cyclospora cayetanensis. Emerg Infect Dis. 2016;22(8):1464-7.  [PMID:27433881]

    Comment: MLS described facilitating investigations into outbreaks.
    

13. Zimmer SM, Schuetz AN, Franco-Paredes C. Efficacy of nitazoxanide for cyclosporiasis in patients with sulfa allergy. Clin Infect Dis. 2007;44(3):466-7.  [PMID:17205465]

    Comment: A case report of a woman with sulfa allergy and Cyclospora cayetanensis infection who responded (clinical and microbiologic cure documented) with 7 days of nitazoxanide.
    

14. Diaz E, Mondragon J, Ramirez E, et al. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg. 2003;68(4):384-5.  [PMID:12875284]

    Comment: This non-randomized, observational study suggests that nitazoxanide may have some efficacy in treating Cyclospora infection. However, there is no comparison with placebo or other treatments, so it is impossible to determine whether cure rates include spontaneous recovery.
    

15. Verdier RI, Fitzgerald DW, Johnson WD, et al. 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. 2000;132(11):885-8.  [PMID:10836915]

    Comment: This is an important clinical trial in which TMP-SMZ is shown to be superior to ciprofloxacin for treatment and prophylaxis of Cyclospora in HIV-infected people in Haiti; ciprofloxacin is less effective with lower clinical and parasitological cure rate, it may still be useful.
    

16. 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. 1995;345(8951):691-3.  [PMID:7885125]

    Comment: Demonstrates the efficacy of TMP/SMX for treating Cyclospora infection in travelers and expatriates who developed an infection in Nepal.
    

17. Ortega YR, Sterling CR, Gilman RH, et al. Cyclospora species--a new protozoan pathogen of humans. N Engl J Med. 1993;328(18):1308-12.  [PMID:8469253]

    Comment: This is the first solid demonstration of this organism as an infection of humans. Landmark paper.
    

Media

Figure 1

Cyclospora. Oocyst shown adjacent to sporulating oocyst with two sporocysts (A). Rupture yields two immature sporocysts (B). Infective parasitic stages seen in (C).

Source Credit: CDC/DPDM

Lifecycle Cyclospora

Source: CDC

Cyclospora oocysts

Source CDC