Cyclosporiasis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]

Cyclosporiasis is an intestinal illness caused by the protozoan Cyclospora cayetanensis, which is transmitted by feces or feces-contaminated fresh produce and water. Outbreaks have been reported in imported raspberries. Fortunately it is not spread from person to person. It is commonly the cause of diarrhea for many travelers.

When freshly passed in stools, the oocyst is not infective (thus, direct fecal-oral transmission cannot occur; this differentiates Cyclospora from another important coccidian parasite, Cryptosporidium). In the environment, sporulation occurs after days or weeks at temperatures between 22°C to 32°C, resulting in division of the sporont into two sporocysts, each containing two elongate sporozoites. Fresh produce and water can serve as vehicles for transmission and the sporulated oocysts are ingested (in contaminated food or water). The oocysts excyst in the gastrointestinal tract, freeing the sporozoites which invade the epithelial cells of the small intestine. Inside the cells they undergo asexual multiplication and sexual development to mature into oocysts, which will be shed in stools. The potential mechanisms of contamination of food and water are still under investigation.

Cyclospora cayetanensis has been only recently identified as a single-celled coccidian parasite. The species designation was given in 1994 to Peruvian isolates of human-associated Cyclospora. It appears that all human cases are caused by this species.

Cyclospora cayentanensis must be differentiated from other diseases that cause watery diarrhea, loss of appetite and abdominal pain, such as viral gastroenteritis (adenovirus, rotavirus, norovirus), bacterial infections (bacillus cereus, clostridium perfringens, vibrio cholerae) or other protozoan infections (entamoeba histolytica, isosporiasis, cryptosporidium parvum).

Cyclosporiasis occurs in many countries, but the disease seems to be most common in tropical and subtropical regions. In areas where cyclosporiasis has been studied, the risk for infection is seasonal. However, no consistent pattern with respect to environmental conditions such as temperature or rainfall has been identified.

People of all ages are at risk for infection. Persons living or traveling in tropical or subtropical regions may be at increased risk because cyclosporiasis is endemic (found) in some developing countries. Foodborne outbreaks of cyclosporiasis in the United States and Canada have been linked to various types of imported fresh produce.

The symptoms usually start within one week of ingestion of contaminated food and water. If left untreated, symptoms may persist for weeks and months. This infection is not life threatening and is rarely associated with complications. People living in endemic area might have asymptomatic infections.

Symptoms of Cyclosporiasis begin 7 days following ingestion of water and food contaminated with sporulated oocysts. The most common symptom is watery diarrhea. Other symptoms include loss of appetite, cramping, flatulence, fatigue, low-grade fever, nausea and vomiting.

The diagnosis of Cyclosporiasis is based on the history and symptoms. There are no specific physical findings for Cyclospora infection. Non specific signs such as dehydration, fatigue, abdominal tenderness and fever may be present.

The diagnosis of cyclospora infection is confirmed by examining stool specimens. Several stool samples are require for a more precise identification of the oocysts. Laboratory techniques used to detect the cyclospora oocytes in stool include acid-fast staining, ultraviolet (UV) fluorescence microscope, and polymerase chain reaction (PCR) analysis.^[1]

Trimethoprim-sulfamethoxazole (TMP-SMX), or Bactrim, Septra, or Cotrim, is the treatment of choice.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). Anti-diarrheal medicine may help reduce diarrhea, but a health care provider should be consulted before such 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.^[2]

The main preventive measure against cyclosporiasis is to avoid unclean water and food that are contaminated with feces. Wash, prepare and store are the recommendations for handling fruits and vegetables to prevent transmission.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Cyclospora cayetanensis infects epithelial cells of the gastrointestinal tract, especially those of the duodenum and jejunum. It is transmitted through the fecal-oral route. C. cayetanensis is excreted in stool in its noninfectious form, and requires certain environmental conditions, such as temperatures of 23-32ºC, to sporulate and become infectious. Once ingested, from contaminated water and/or food, sporozoites are released from oocysts, and infect gastrointestinal cells. It causes histological changes in the infected mucosa, which may include: loss of the brush border appearance, villous atrophy, crypt hyperplasia, and vacuolization of the tips of the villi.

Unsporulated oocysts of Cyclospora cayetanensis are excreted from infected individuals. When freshly passed in stool, the oocyst is not infective (thus, direct fecal-oral transmission cannot occur, which differentiates Cyclospora from other important coccidian parasites such as Cryptosporidium). Under adequate temperatures (23-32ºC), oocysts take about 7-15 days to sporulate and become infectious. After ingestion, oocysts excyst to release elongated sporozoites. Sporozoites then infect epithelial cells of the gastrointestinal tract, particularly those of the duodenum and jejunum. The sporozoites undergo asexual reproduction giving rise to meronts type I and II, which then differentiate into gametocytes. Gametocytes are fertilized to produce a zygote.^[1][2] Inside cells, zygotes undergo asexual reproduction and development to mature into oocysts, which are shed in the stool.^[3] C. cayetanensis oocysts have also been isolated from non-gastrointestinal sites, such as sputum, especially in immunocompromised patients with HIV and concomitant TB. This led to the hypothesis that C. cayetanensis may be an opportunistic pathogen.^[4]

C. cayetanensis is transmitted by the fecal-oral route. Individuals are infected with Cyclospora by ingesting sporulated oocysts (infective form of the parasite). This occurs most commonly when food or water contaminated with human fecal material is consumed. The parasite is shed in the feces of infected persons in the unsporulated oocyst form (non-infective) and, in a favorable environment, sporulate and become infective. Therefore, direct person-to-person transmission is unlikely, as is transmission via ingestion of newly contaminated food or water.^[3][2]

C. cayetanensis infects epithelial cells of the small intestine, especially those of the jejunum. Infected patients may have evidence of intestinal injury on endoscopy such as mucosal erythema.^[2] Histologic samples of small bowel of these patients demonstrate involvement of the lamina propria and neutrophilic infiltration in some cases. Cyclosporiasis may demonstrates evidence of chronic inflammation, with plasma cells observed in mucosal samples of infected patients.^[5] Classically, immunocompromised patients are more prone to develop chronic inflammation of the gastrointestinal epithelium.^[2]

Infected epithelial cells of the gastrointestinal tissue may demonstrate the following changes:^[5][2]

• Loss of brush border appearance
• Vacuolization of the tips of the villi
• Epithelial changes from columnar to cuboid
• Villous atrophy (partial)
• Crypt hyperplasia

• Increased length of crypts and increased mitosis
• Shortened villi

• Absence of parasitic vacuoles in biopsied samples

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Cyclospora cayetanensis is a protozoan that causes disease in humans, and possibly in other primates. It has also been isolated from the feces of other animals such as ducks and chickens. Due to the spherical shape of C. cayetanensis sporocytes, it was placed in the Cyclospora genus. It has a double layered wall that gives it resistance against disinfectants and adhesins which are responsible for its adherence characteristics. The bacteria show tropism for epithelial cells of the small intestine, especially of the duodenum and jejunum.

Eukaryota; Alveolata; Apicomplexa; Conoidasida; Coccidia; Eucoccidiorida; Eimeriorina; Eimeriidae; Cyclospora^[3]

Cyclospora cayetanensis is an obligate intracellular apicomplexan, cyst-forming coccidian protozoan, of the family of Eimeriidae, which commonly causes self-limiting diarrhea. Morphologically C. cayetanensis has spherical oocysts that are between 7.5 and 10 micrometers in diameter that also have a 50 nanometer thick bilayered wall with an outer threadlike coat that has been called a wrinkle by some researchers.^[4][5][6]

According to a phylogenetic analysis performed with the 18S rRNA gene, in the Cyclospora species isolated from a group of baboons, this species, although different, was proved to be similar to the C. cayetanensis that infects humans. These two species were then documented was belonging to the same clade of the Eimeria species.^[7] Other three species of Cyclospora were also identified in non-human primates and characterized with the SSU rRNA analysis, later that year. Because there are morphologically similar, there can not be differentiated by light microscopy.^[8] These species: C. cercopitheci, C. colobi and C. papionis were identified in green monkeys, colobus monkeys, and baboons, respectively. C. cayetanensis and these three other species of Cyclospora all share the characteristic of being host-specific.^[5][5]

It is not known the exact conditions and location required for the sporulation of oocysts in the natural environment, however, these data would help to understand and predict the distribution and seasonality of C. cayetanensis. Due to its double-layered wall it is highly resistant, particularly to disinfectants used during food processing. This resistance along with its binding affinity to certain produce, explains the risks associated with contaminated foods. The adhesive properties of C. cayetanensis are stronger than those of the oocysts of Giardia or Cryptosporidium, however, the responsible adhesins are yet to be identified.^[5]

Cyclospora cayetanensis shows tropism for epithelial cells of the small intestine, especially for the jejunum.^[5]

C. cayetanensis is an host specific parasite that is able to infect humans. Cyclospora oocysts have also been isolated from the feces of several animals, such as ducks, chickens and dogs.^[9][10][11] Attempts to identify and to infect different animals with C. cayetanensis have failed.^[12] Certain shellfish may acquire C. cayetanensis from contaminated waters, and concentrate its oocyst for several days.^[13]

Cyclospora cayetanensis infection must be differentiated from other causes of viral, bacterial, and parasitic gastroentritis.

8Small bowel diarrhea: watery, voluminous with less than 5 WBC/high power field

Large bowel diarrhea: Mucousy and/or bloody with less volume and more than 10 WBC/high power field
† It could be as high as 1000 based on patient’s immunity system.

The table below summarizes the findings that differentiate inflammatory causes of chronic diarrhea^{[14][15][16][17][17]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Cyclospora cayentanensis must be differentiated from other diseases that cause watery diarrhea, loss of appetite and abdominal pain, such as viral gastroenteritis (adenovirus, rotavirus, norovirus), bacterial infections (bacillus cereus, clostridium perfringens, vibrio cholerae) or other protozoan infections (entamoeba histolytica, isosporiasis, cryptosporidium parvum).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2] Ammu Susheela, M.D. [3] Alejandro Lemor, M.D. [4]

Cyclosporiasis occurs in many countries, but the disease seems to be most common in tropical and subtropical regions. In areas where cyclosporiasis has been studied, the risk for infection is seasonal. However, no consistent pattern with respect to environmental conditions such as temperature or rainfall has been identified.

• Cyclosporiasis is an intestinal illness caused by consuming food or water contaminated with the Cyclospora parasites.
• The major symptom is watery diarrhea lasting a few days to a few months. Additional symptoms may include loss of appetite, fatigue, weight loss, abdominal cramps, bloating, increased gas, nausea, vomiting and a low fever. Symptoms may come and go multiple times over a period of weeks
• People become infected with Cyclospora by ingesting sporulated oocysts, which are the infective form of the parasites. This most commonly occurs when food or water contaminated with feces is consumed. An infected person sheds unsporulated (immature, non-infective) Cyclospora oocysts in the feces. The oocysts are thought to require days to weeks in favorable environmental conditions to sporulate and become infective. Therefore, direct person-to-person transmission is unlikely, as is transmission via ingestion of newly contaminated food or water.
• Cyclosporiasis occurs in many countries, but it seems to be most common in tropical and subtropical regions. In areas where Cyclosporiasis has been studied, the risk for infection is seasonal. However, no consistent pattern has been identified regarding the time of year or the environmental conditions, such as temperature or rainfall.
• In the United States, foodborne outbreaks of Cyclosporiasis since the mid-1990s have been linked to various types of imported fresh produce, including raspberries, basil, snow peas, and mesclun lettuce; no commercially frozen or canned produce has been implicated. U.S. cases of infection also have occurred in persons who traveled to Cyclospora-endemic areas. To reduce the risk for infection, travelers should take precautions. Travelers also should be aware that treatment of water or food with chlorine or iodine is unlikely to kill Cyclospora oocysts.
• Oocytes of Cyclospora has been isolated from stools of children and adults. They are found mainly in the stool of residents and travelers from developing countries like North central and South America, South east Asia, Australia, Carribean, Europe and Indian sub-continent.
• Outbreaks have been reported from North and South America and Nepal. 1996 outbreak reported 1465 cases in Canada and USA during spring and summer and some occassions where Raspberries have been served.
• Sporadic cases have been reported from many countries, in immunocompetent people with no prior travel history.
• They are also common in people with HIV

The polymorphic area of the genome has been studied extensively as a part of investigation in their role in epidemiology. 18S rRNA has been used to differentiate Cyclospora from other parasites. The high sequence variability found in people in United states without a prior history of travel suggest an endemic focus for Cyclospora in United States.^[1]

• On August 26, 2014, CDC had been notified of 304 ill persons with confirmed Cyclospora infection in 2014
• 207 out of the 304 ill persons from the following states had no history of international travel within two weeks before onset of illness: Arkansas, California, Connecticut, Florida, Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, Montana, Nebraska, Pennsylvania, New Jersey, New York (and New York City), Texas, Virginia, Wisconsin, and Washington.
• Among 183 persons with available information, 7 (4%) have reported being hospitalized. No deaths have been reported.

• Among 204 persons with available information, patients with Cyclosporiasis range in age from 3 to 88 years, with a median age of 49 years.

• Among 204 persons with available information, 115 (56%) patients with Cyclosporiasis are female.

• On June 28, 2013, CDC was notified of 2 laboratory-confirmed cases of Cyclospora infection in Iowa residents who had become ill in June and did not have a history of international travel during the 14 days before the onset of illness.
• Since that date, CDC has been collaborating with public health officials in multiple states and the US Food and Drug Administration (FDA) to investigate an outbreak of cyclosporiasis. As of July 18, 2013, CDC has been notified of more than 200 cases of Cyclospora infection in residents of multiple states, including Iowa, Nebraska, Texas, and Wisconsin.
• Illinois has also notified CDC of one case that may have been acquired out of state.
• Most of the illness onset dates have ranged from mid-June through early July.
• At least 8 persons reportedly have been hospitalized.
• No food items have been implicated to date, but public health authorities are pursuing all leads.
• Previous outbreak investigations have implicated various types of fresh produce. It is not yet clear whether the cases from all of the states are part of the same outbreak.
• No common events (e.g., social gatherings) have been identified among the case patients.

• Age ranges from less than 1 year to 94 years, with a median age of 52 years.

• Fifty-eight percent (58%) of patients with Cyclosporiasis were female.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

People of all ages are at risk for infection. Persons living or traveling in tropical or subtropical regions may be at increased risk because cyclosporiasis is endemic in some developing countries. Foodborne outbreaks of cyclosporiasis in the United States and Canada have been linked to various types of imported fruit and vegetables.

• Contaminated water or food (see table below)
• Low socioeconomic status
• Poor sanitation
• Recent history of travel to endemic areas
• Residence in endemic areas (see table below)^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

There are no specific screening test indicated for Cyclospora.

IOWA department of public health has updated guidelines for conditions where testing of cyclospora is appropriate. Screening of Cyclospora should be done only if any of the following conditions apply.

• Patient’s diarrhea began in June, or
• Patient has prolonged diarrhea (greater than 5 days duration – eliminating the more common causes of diarrheal illness), accompanied by symptoms such as fatigue and anorexia, or
• Patient is a traveler with watery diarrhea returning from a part of the world where Cyclospora is endemic (such as Nepal, Guatemala or Peru).

In such conditions, stool specimen is tested for Cyclospora. ^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Manifestations of cyclosporiasis vary according to the endemicity of the country. Initial symptoms occur about 7 days after the ingestion of bacteria in contaminated food or water. If left untreated, these may persist from weeks to months. Symptoms may include: fever; anorexia; nausea; fatigue; abdominal cramping; and diarrhea. Younger and elderly patients usually experience more severe and prolonged symptoms. Although rare, potential complications include: malabsorption; cholecystitis; Guillain-Barré syndrome; and Reiter’s syndrome. This infection is not life threatening, however, if untreated, severe cases of diarrhea may lead to dehydration and electrolyte imbalance, which may compromise the prognosis.

Patients with cyclosporiasis may be asymptomatic, or present only with milder and short lasting forms of the disease, particularly those who live in endemic areas.^[1] Symptomatic disease is more common in non endemic regions. For patients who develop symptoms following the ingestion of sporulated oocysts of C. cayetanensis, the typical incubation period is about 7 days.^[2][3] Cyclosporiasis commonly presents with the following symptoms:^{[4][2][3][5][6]}

• Anorexia
• Nausea
• Flatulence
• Fatigue
• Abdominal cramping
• Diarrhea
• Low-grade fever
• Weight loss

Without treatment, patients with cyclosporiasis may have symptoms for several weeks to several months. Some of these symptoms, such as diarrhea, can return, and others, such as muscle aches and fatigue, may continue after the gastrointestinal manifestations have resolved.^[1]

In general, children and elderly patients experience more severe symptoms of cyclosporiasis.

Symptoms are also more severe and prolonged in HIV-positive patients. ^[6][7][8]

Although rare, complications from cyclosporiasis may include:^[7][9]

• Malabsorption
• Cholecystitis
• Guillain-Barré syndrome^[10]
• Reiter’s syndrome^[11]

In general, infection with C. cayetanensis is not a life-threatening condition. However, untreated patients may experience more severe forms of the disease, with severe and prolonged diarrhea, which may lead to important dehydration and electrolyte imbalance, that may have a poor prognosis.^[1]

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