Cyclospora cayetanensis is a coccidian parasite that causes a diarrheal disease called cyclosporiasis in humans and possibly in other primates. Originally reported as a novel pathogen of probable coccidian nature in the 1980s^[1] and described in the early 1990s,^[1] it was virtually unknown in developed countries until awareness increased due to several outbreaks linked with fecally contaminated imported produce. C. cayetanensis has since emerged as an endemic cause of diarrheal disease in tropical countries and a cause of traveler's diarrhea and food-borne infections in developed nations.^[1] This species was placed in the genus Cyclospora because of the spherical shape of its sporocysts. The specific name refers to the Cayetano Heredia University in Lima, Peru, where early epidemiological and taxonomic work was done.^[2]

The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. (September 2018)

Quick Facts Cyclospora cayetanensis, Scientific classification ...

Cyclospora cayetanensis
Cyclospora cayetanensis oocysts
Scientific classification
Domain:	Eukaryota
Clade:	Diaphoretickes
Clade:	SAR
Clade:	Alveolata
Phylum:	Apicomplexa
Class:	Conoidasida
Order:	Eucoccidiorida
Family:	Eimeriidae
Genus:	Cyclospora
Species:	C. cayetanensis
Binomial name
Cyclospora cayetanensis Ortega, Gilman & Sterling, 1994

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As originally recognized by Markus & Frean (1993),^[3] the first published report of Cyclospora cayetanensis in humans appears to be by Ashford (1979), who found unidentified Isospora-like coccidia in the feces of three individuals in Papua, New Guinea. They referenced Ashford's article. The photomicrographs in his paper reveal an organism morphologically identical to that seen nowadays. Markus had perceived the probable coccidial nature of Cyclospora in the 1980s but did not formally publish his ideas on the matter. Later, Narango et al. (1989) reported what may be the same organism from several Peruvians with chronic diarrhea and termed the organism Cryptosporidium muris–like. Other investigators thought the unsporulated oocysts appeared more similar to cyanobacteria, and the name "cyanobacterium-like body" or CLB became prevalent in the literature (occasionally, authors also used the term "coccidian-like body", or CLB). Eventually, Ortega et al. (1992) published an abstract reporting that they had sporulated and excysted the oocysts, resulting in placement of the parasite in the genus Cyclospora. They also created the name Cyclospora cayetanensis at this time. However, since no morphologic information was presented in the abstract, C. cayetanensis technically became a nomen nudum (a named species without a description). Although Ortega et al. (1993) later published additional details about this coccidian, a complete morphologic description was not published to validate the name until 1994.^[4] Thus, the correct name for this parasite is Cyclospora cayetanensis Ortega, Gilman, & Sterling, 1994, and the etymology of the nomen triviale is derived from Cayetano Heredia University in Lima, Peru. During this two-year period when C. cayetanensis was a nomen nudum, anyone wishing to publish a complete morphologic description and change the name would have been free to do so.^[2]

Cyclospora cayetanensis is an apicomplexan, cyst-forming coccidian protozoan that causes a self-limiting diarrhea. In terms of morphology, It has spherical oocysts that are between 7.5 and 10 μm in diameter that also have a 50-nm-thick wall with an outer thread-like coat that has been called a wrinkle by some researchers. The oocyst formula is O.2.2 because one oocyst contains two sporocysts and each sporocyst contains two sporozoites.^[5]

The only confirmed hosts for C. cayetanensis are humans. The protozoan lives out its lifecycle intracellularly within the host's epithelial cells and gastrointestinal tract. Infection is transmitted through the fecal-oral route, and begins when a person ingests oocysts in feces-contaminated food or water. Various chemicals in the host's gastrointestinal tract cause the oocysts to excyst and release sporozoites; generally, two are observed per oocyst. After these sporozoites invade the epithelial cells, they undergo merogony, a form of asexual reproduction that results in many daughter merozoites. These daughter cells may either infect new host cells and initiate yet another round of merogony or take on a sexual track via gametogony: Daughter merozoites become male macrogamonts—which form many microgametes—and female macrogamonts. After fertilization has occurred via male microgamete fusion with female macrogamont, the zygote matures into an oocyst and ruptures the host cell, from which point it is passed with the stool. The oocysts that are passed are not, however, immediately infectious. Sporulation can take from one to several weeks, meaning person-to-person transmission is not a likely event. This differentiates C. cayetanensis from Cryptosporidium parvum—a closely related organism that causes a similar disease—since C. parvum oocysts are immediately infectious upon release from the host.^[6]

C. cayetanensis causes gastroenteritis, with the extent of the illness varying based on age, condition of the host, and size of the infectious dose. Symptoms include "watery diarrhea, loss of appetite, weight loss, abdominal bloating and cramping, increased flatulence, nausea, fatigue, and low-grade fever", though this can be augmented in more severe cases by vomiting, substantial weight loss, excessive diarrhea, and muscle aches. Typically, patients with a persistent watery diarrhea lasting over several days may be suspected of harboring the disease, especially if they have traveled to a region where the protozoan is endemic. The incubation period in the host is typically around a week, and illness can last six weeks before self-limiting. Unless treated, illness may relapse. The more severe forms of the disease can occur in immunocompromised patients, such as those with AIDS.^[7] Human cyclosporiasis is clinically similar to cryptosporidiosis, isosporiasis, giardiasis and microsporidiosis because of the similar clinical features. Flu like syndrome with myalgias and arthralgias may precede the onset of diarrhea. Fever is low grade and is unusual. There is presence of moderate to severe dehydration, compensatory tachycardia, systolic blood pressure (SBP<90 mmHg) and decreased skin turgor may occur. But mild infection produces few or no clinical symptoms. The immune system may determine the appearance of symptoms; that is, from symptomatic to asymptomatic stage depends on resistivity of the immune system.^[8]

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 a marked seasonality that is poorly understood, whereas North American outbreaks occur most frequently in late spring and summer, correlating with increased import of produce from the tropics.^[2] Consuming food or water while visiting developing countries is a well-documented way of developing traveler's diarrhea. Travelers are often warned against such actions, but over 70 percent of certain produce items consumed in the United States are imported from developing countries, making "traveler's diarrhea" possible without international travel.^[9] Since oocysts are shed in the feces of infected persons and then must mature in the environment 2–14 days before they can become infectious, it is unlikely for a person to get an infection directly from another person, such as an infected food handler.^[1]

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 polymerase chain reaction (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.^{[citation needed]}

Except for PCR amplification, once a sample with suspected oocysts has been recovered, standard tests are followed to identify C. cayetanensis. These tests include phase contrast microscopy to check for the spherical oocysts described earlier, modified acid-fast staining to check for variable staining (from pale to red), and autofluorescence with UV lights. 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 exams 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%.^[10]

C. cayetanensis has been confused with other protozoan infections in the past, most commonly being misidentified as Cryptosporidium parvum. Several differences can be noted between the two, however, to ensure proper diagnosis. These differences include: size difference—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.^{[citation needed]}

Cases of C. cayetanensis infection often go unexplained, partly because of the difficulties associated with epidemiologic investigations of such cases and the lack of genotyping methods. Recent attempts at a better genotyping characterisation include multilocus sequence typing based on microsatellite markers ^[11] and single nucleotide polymorphisms (SNPs) of nuclear markers.^[12]

Most people who have healthy immune systems will recover without treatment. If not treated, the illness may last for a few days to a month or longer. Symptoms may seem to go away and then return one or more times (relapse). Antidiarrheal medicine may help reduce diarrhea, but consult with a health care provider before the medicine is taken. People who are in poor health or who have weakened immune systems may be at higher risk for severe or prolonged illness.^[13] To date, the most effective drug for the treatment of the protozoan is a seven-day course of oral trimethoprim-sulfamethoxazole (TMP-SMX). Effects of the drug include a significant decrease in the duration of oocyst excretion, cessation of diarrhea, and stool samples negative for oocysts within two to three days.^[13] TMP-SMX is classified as a Category C during pregnancy, meaning potential adverse effects (such as teratogenic or embryocidal or other) could results and should only be given if the potential benefit significantly justifies the risk. The drug 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.^[14] No highly alternative antibiotic regimen has been discovered yet for patients who possess a sulfa-allergy.^[15]

No vaccine against this pathogen is available.^[16] Since infection occurs via fecally contaminated food and water in endemic environments, several simple solutions have been suggested for the prevention of C. cayetanensis infections. The simplest is to warn travelers not to visit regions where the protozoan is endemic (in general, tropical and subtropical regions where sanitation is poor, such as Peru, Brazil, and Haiti), especially when the season is best for spreading: Travelers also should be aware that treatment of water or food with chlorine or iodine is unlikely to kill Cyclospora oocysts.^[17] Additionally, better health practices in the originating agricultural setting—such as making sure produce watering systems are not pulling water that has access to human feces. Additionally, using filtering systems such as a 1 micron absolute carbon filtration system will reduce the presence of Cyclospora, drastically decreasing the incidence of the spread of this parasite.^[1] 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 prior to consumption. However, simply washing foods does not remove 100% of the oocysts present.^[2]