cyclosporiasis

Signs and symptoms

Cyclospora cayetanensis causes gastroenteritis, with the extent of the illness varying based on age, condition of the host, and size of the infectious dose. Symptoms of cyclosporiasis include watery diarrhea, loss of appetite, weight loss, abdominal bloating and cramping, increased flatulence, nausea, fatigue, and low-grade fever. This can be augmented occasionally by vomiting, substantial weight loss, excessive diarrhea, and muscle aches.

The incubation period in the host is typically around a week after consuming infectious oocysts, and illness can last up to six weeks before self-limiting. Unless treated, illness may relapse. Disease tends to be more severe in vulnerable people, including infants, the elderly, people who do get sick but do not reside in endemic countries, and people with a weakened immune system, such as people with HIV/AIDS. Dehydration and malnutrition may complicate cases of cyclosporiasis when severe diarrhea occurs.

The occurrence of moderate to severe dehydration is uncommon, but when present, symptoms may include symptoms such as compensatory tachycardia, low blood pressure, and decreased skin turgor. However, clinical symptoms of dehydration are inconsistent, and may be very subtle even when dehydration is severe.

Immunocompromised patients are also known to sometimes exhibit nonspecific symptoms of influenza-like illness.

Cause

Persons living or traveling in developing tropical or subtropical areas may be at an increased risk of acquiring C. cayetanensis, as it is endemic in these areas. Infections in endemic regions tend to show seasonality that is poorly understood, whereas North American outbreaks occur most frequently in late spring and summer, with warm temperatures being necessary for large numbers of oocysts to sporulate. Consuming unclean food or water while visiting developing countries is a well-documented way of developing travelers' diarrhea, though produce imported from developing countries may also cause it without international travel. Oocysts are often present in the environment as a result of using contaminated water or human feces as fertilizer.

Since oocysts are shed in the feces of infected persons and then must mature in the environment for 2–14 days before they can become infectious, a person getting an infection directly from another person, such as an infected food handler, is unlikely.

At the beginning of the AIDS epidemic in the early 1980s, cyclosporiasis was identified in stool samples of people with AIDS alongside Cryptosporidium, which is an important opportunistic infections in this group.

Diagnosis

Diagnosis can be difficult due to the lack of recognizable oocysts in the feces. PCR-based DNA tests and acid-fast staining can help with identification. A history of recent consumption of foods more likely to be contaminated with Cyclospora oocysts, such as fresh leafy greens, basil, cilantro, or fresh berries, within two weeks of a compatible diarrheal illness during the summer should prompt suspicion for cyclosporiasis.

Except for PCR amplification, once a sample with suspected oocysts has been recovered, standard tests are followed to identify C. cayetanensis; phase contrast microscopy for the spherical oocysts, modified acid-fast staining for variable staining (from pale to red), and autofluorescence with ultraviolet lights are used. Obtaining these oocysts is usually the challenge, though recent studies show easier methods of obtaining them. In a recent study on different techniques used in fecal examinations to identify oocysts, centrifuging a sample of feces in a sucrose solution and then transferring a small amount to a slide was found to be remarkably effective—both in oocysts found and relative ease of labor—in detecting C. cayetanensis oocysts. Indeed, the paper concluded the positive samples obtained were around 84%.

At least one nucleic acid amplification test is available commercially in both the United States and Europe, and several additional testing panels are approved for use in Europe but not the United States.

Challenges

Due to its small size, intracellular habitat, and inability to properly take up many histological stains, diagnosis of C. cayetanensis can be very difficult. Four methods have thus far been established for positive diagnosis of the protozoan - microscopic detection in stool samples of oocysts, recovering oocysts in intestinal fluid/small bowel biopsy specimens, demonstration of oocyst sporulation, and amplification by PCR of C. cayetanensis DNA. Since detection is so hard, one negative result should not discount the possibility of C. cayetanensis; tests involving fresh stool samples over the next few days should also be considered.

C. cayetanensis has been confused with other protozoan infections in the past, most commonly being misidentified as Cryptosporidium parvum. Several differences can be noted, including size—C. parvum is smaller; differing results from modified acid-fast staining—C. parvum has consistent red staining, whereas C. cayetanensis shows variable staining; and autofluorescence under UV light—C. cayetanensis exhibits this, whereas C. parvum does not.

Prevention

No vaccine against this pathogen is available. Infection occurs via fecally contaminated food and water, and cooking food and boiling water is the only way to kill Cyclospora. Washing hands with soap and water before preparing food and washing fruits and vegetables under running water can reduce risk, but the pathogen cannot be reliably removed. It is not likely to be killed by routine sanitization.

Other advice warns travelers not to visit regions where the protozoan is endemic (tropical and subtropical regions with poor sanitation, such as Peru, Brazil, and Haiti), especially when conditions are most conducive to Cyclospora's spread. Treatment of water or food with chlorine or iodine is unlikely to kill Cyclospora oocysts. Better health practices in the originating agricultural setting such as ensuring produce-watering systems are not pulling water that has access to human feces can reduce spread. Additionally, filtering systems such as 1-micron absolute carbon will reduce the presence of Cyclospora, drastically decreasing the incidence of the spread of this parasite. The odds of becoming infected with Cyclospora, and many other foodborne pathogens, can be greatly diminished by thoroughly washing fruits and vegetables in clean water before consumption. However, simply washing food does not remove 100% of the oocysts present.

Treatment

Most people who have healthy immune systems recover without treatment. If untreated, the illness may last for a few days to a month or longer. Signs and symptoms may seem to go away and then return one or more times (relapse). Antidiarrheal medicine may help reduce diarrhea, but consulting a health-care provider before taking it is recommended. People who are in poor health or who have weakened immune systems may be at higher risk for severe or prolonged illness.

First-line

Trimethoprim/sulfamethoxazole (TMP-SMX), also known as co-trimoxazole, is the treatment of choice. The recommended dose for immunocompetent adults is two doses of 160 mg TMP + 800 mg SMX per day for 7–10 days; immunocompromised adults typically receive the same dose, but for longer. The cure rate with TMP-SMX is around 96%.

Effects of TMP-SMX include a decrease in the duration of oocyst excretion, cessation of diarrhea, and stool samples negative for oocysts within two to three days. TMP-SMX is classified as Category C during pregnancy, meaning potential adverse effects (such as teratogenic or embryocidal or other) could result, and it should only be given if the potential benefit justifies the risk. It should be avoided near-term, as high potentials exist for hyperbilirubinemia and kernicterus in newborns. Additionally, TMP-SMX can be excreted in breast milk, which is compatible in healthy, full-term newborns, but should be avoided in premature, ill, stressed, or jaundiced infants.

Alternatives

For people unable to take trimethoprim/sulfamethoxazole (e.g., due to a sulfonamide allergy), nitazoxanide, or ciprofloxacin are recommended as alternative but much less effective agents. Some sources consider ciprofloxacin to be broadly ineffective.

Many common antiparasitic drugs are ineffective against Cyclospora, including: albendazole, azithromycin, tetracycline, doxycycline, metronidazole, trimethoprim (without sulfamethoxazole), tinidazole, quinacrine, nalidixic acid, and diloxanide furoate.

Prognosis

Most cases of cyclosporiasis have only mild symptoms or are entirely asymptomatic. However, like other watery diarrheal illnesses (e.g. cholera), substantial health risks or death may result from severe dehydration. The risk of death due to dehydration or malnutrition is greatest in infants, elderly people, young children, and people with major comorbidities; older children and average adults have symptoms less often and of lower severity. Even in the higher-risk group, though, mortality is low overall. The 2020 outbreak in the United States, with 1,241 confirmed cases, had no reported deaths.

Rare cases have been reported of cyclosporiasis causing more severe disease manifestations that are not linked to dehydration, especially in immunocompromised patients. The parasite is capable of infecting the biliary tract and causing cholecystitis, and isolated case reports have identified other uncommon complications in some individuals.

Epidemiology

Tropical and subtropical regions

Cyclosporiasis is a common disease in the tropics, contributing to a total worldwide prevalence in humans around 3.5%.

The first formally recorded cases of cyclosporiasis in humans were as recently as 1977, 1978, and 1979. They were reported by Ashford, a British parasitologist who discovered three cases while working in Papua New Guinea. Ashford found that the parasite had very late sporulation, from 8–11 days, making the illness difficult to diagnose. When examining feces, the unsporulated oocysts can easily be mistaken for fungal spores, thus are overlooked.

Cyclosporiasis infections have been reported in Nepal. In one study, Ghimire et al. collected samples of vegetables, sewage, and water from ponds, rivers, wells, and municipal taps in the Kathmandu Valley from 2002 to 2004. They found Cyclospora in radish, cauliflower, cabbage, and mustard leaves, as well as sewage and river water. This first epidemiological study determined the seasonal character of cyclosporiasis outbreaks in Nepal during the rainy season, from May to September.

United States

Summertime outbreaks of cyclosporiasis have occurred frequently in the United States since at least the 2010s, although earlier outbreaks have also occurred, such as a 1990 outbreak in Chicago caused by contaminated tap water. Between 2018 and 2021, about 6,000 endemically acquired cases of cyclosporiasis were diagnosed and tracked by the Centers for Disease Control and Prevention (CDC).

In the United States, Cyclospora prevalence was tracked through the Foodborne Diseases Active Surveillance Network (FoodNet) system until 2025, when budget cuts resulted in the CDC no longer mandating reporting of the disease.

Outbreaks in the U.S. have been linked to consumption of fresh produce, mainly imported but also domestic.

Although Cyclospora initially was thought to be confined to tropical and subtropical regions, cyclosporiasis outbreaks are becoming more frequent in North America. According to the CDC, at least 11 documented cyclosporiasis outbreaks have occurred in the U.S. and Canada since the 1990s. The CDC also recorded 1,110 laboratory-confirmed sporadic instances of cyclosporiasis from 1997 to 2008.

Foodborne outbreaks of cyclosporiasis have been linked to various types of imported fresh produce, including raspberries, basil, snow peas, mesclun lettuce, and cilantro; no commercially frozen produce has been implicated to date. U.S. foodborne outbreaks of cyclosporiasis that occurred before 2000 were summarized previously, as were the major documented outbreaks in 2013 and 2014. Foodborne outbreaks during 2000–2014 are summarized in the table. The table provides information about 31 reported foodborne outbreaks of cyclosporiasis that occurred in the United States during 2000–2014; the total case count was 1,562. No outbreaks were reported in 2003, 2007, or 2010. Overall, a median of two outbreaks were reported per year, with a median of 20 cases per outbreak (range, 3 to 582 cases). Although the outbreaks occurred during eight months (December through July), the peak months were May, June, and July. As indicated in the table, a food vehicle of infection was identified for 15 of the 31 outbreaks.

* The entries in the first three columns refer to the known or likely year(s), month(s), and jurisdiction(s) in which the exposure(s) to Cyclospora occurred.