Cyclospora cayetanensis
Encyclopedia
Cyclospora cayetanensis is a protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...

n that causes disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

 in humans, and perhaps other primates. It has been linked in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 from fecally-contaminated imported raspberries
Raspberry
The raspberry or hindberry is the edible fruit of a multitude of plant species in the genus Rubus, most of which are in the subgenus Idaeobatus; the name also applies to these plants themselves...

 and was virtually unknown before about 1990, but has been on the rise since. The health risk associated with the disease is usually confined to adult foreigners visiting endemic regions and acquiring the infection: this is why C. cayetanensis has been labeled as causing “traveler’s diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

.”

This species was placed in the Cyclospora genus because of the spherical shape of its sporocysts. The species name refers to the Cayetano Heredia University
Cayetano Heredia University
Cayetano Heredia University or simply Cayetano Heredia) is a private university located in Lima, Peru. It was named in honor of Cayetano Heredia, one of the eminent Peruvian physicians of the 19th century. The university is overseen by a Board of Trustees and is not actually property of any...

 in Lima, Peru, where early epidemiological and taxonomic work was done.

Characterization

Cyclospora cayetanensis is an apicomplexa
Apicomplexa
The Apicomplexa are a large group of protists, most of which possess a unique organelle called apicoplast and an apical complex structure involved in penetrating a host's cell. They are unicellular, spore-forming, and exclusively parasites of animals. Motile structures such as flagella or...

n, cyst-forming coccidia
Coccidia
Coccidia is a subclass of microscopic, spore-forming, single-celled obligate parasites belonging to the apicomplexan class Conoidasida. Coccidian parasites infect the intestinal tracts of animals, and are the largest group of apicomplexan protozoa....

n protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...

n that causes a self-limiting diarrhea. Morphologically speaking, C. cayetanensis has spherical oocysts that are between 7.5 and 10 micrometer
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...

s in diameter that also have a 50 nanometer thick wall with an outer threadlike coat that has been called a wrinkle by some researchers.

The only hosts C. cayentanensis uses are humans. The protozoan lives out its lifecycle intracellularly within the host’s epithelial cells and gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

. Infection is transmitted through the oral-fecal route, and begins when a person ingests oocysts in fecally 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
Asexual reproduction
Asexual reproduction is a mode of reproduction by which offspring arise from a single parent, and inherit the genes of that parent only, it is reproduction which does not involve meiosis, ploidy reduction, or fertilization. A more stringent definition is agamogenesis which is reproduction without...

 that results in many daughter merozoites. These daughter cells may either infect new host cells and initiate yet another round of merogony, or they can take on a sexual track via gametogony
Gametogonium
A gametogonium is a germ cell that divides into gametocytes during gametogenesis. Male gametogonia are called spermatogonia, and female gametogonia are called oogonia....

: 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
Zygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...

 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 anywhere from one to several weeks, meaning that person-to-person transmission is not a likely problem. This differentiates C. cayentanensis from Cryptosporidium parvum — a closely related organism that causes a similar disease — since C. parvum oocysts are immediately infectious upon release from the host.

Symptoms

C. cayentanensis causes gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...

, 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
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...

, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, fatigue, and low-grade fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

," though this can be augmented in more severe cases by vomiting, substantial weight loss, explosive diarrhea, and muscle aches. Typically, patients who come in 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
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

 in the host is typically around a week, and illness can last six weeks before self-limiting. Unless treated, illness may relapse. It is important to note here that the more severe forms of the disease can occur in immunocompromised
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...

 patients such as those with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

.

Recognition

Due to its small size, intracellular habitat, and inability to properly uptake many histological stains, diagnosis of Cyclospora 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
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 (PCR) of C. cayetanensis DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

. 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.

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 stainability (all the way from pale to red), and autofluorescence
Autofluorescence
Autofluorescence is the natural emission of light by biological entities such as mitochondria and lysosomes, and is used to distinguish the light originating from artificially added fluorescent markers...

 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, it was demonstrated that centrifuging a sample of feces in a sucrose solution and then transferring a small amount to a slide was remarkably effective—both in oocysts found and relative ease of labor—in detecting C. cayetanensis oocysts: indeed, the paper concluded that the total number of positive samples obtained was around 84%.

C. cayetanensis has been confused with other protozoan infections in the past, the most often of which was Cryptosporidium parvum. There are several differences that 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; and autofluorescence under UV light — C. cayetanensis does, C. parvum does not.

Treatment

Though the diarrhea caused by C. cayetanensis is self-limiting, relapses can and do occur. 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 significant decrease in the duration of oocyst excretion and cessation of diarrhea and stool samples negative for oocysts between two and three days. Relapse patients respond promptly to the therapy, and there has been talk of using TMP-SMX as a prophylaxis for HIV/AIDS patients.

Prevention

Since infection occurs via fecally contaminated food and water in endemic environments, there are several simple solutions to suggest for the prevention of C. cayetanensis infections. The simplest one is to warn travelers not to visit regions where the protozoan is endemic (generally tropical and sub-tropical regions such as Peru
Peru
Peru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean....

, Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, and Haiti
Haiti
Haiti , officially the Republic of Haiti , is a Caribbean country. It occupies the western, smaller portion of the island of Hispaniola, in the Greater Antillean archipelago, which it shares with the Dominican Republic. Ayiti was the indigenous Taíno or Amerindian name for the island...

), especially when the disease is in its best season for spreading: such was the reason behind the first reported case of cyclosporiasis
Cyclosporiasis
Cyclosporiasis is an infection with the protozoan Cyclospora cayetanensis, a pathogen transmitted by feces or feces-contaminated fresh produce and water. Outbreaks have been reported due to contaminated raspberries. It is not spread from person to person...

 in Korea
Korea
Korea ) is an East Asian geographic region that is currently divided into two separate sovereign states — North Korea and South Korea. Located on the Korean Peninsula, Korea is bordered by the People's Republic of China to the northwest, Russia to the northeast, and is separated from Japan to the...

. This is not to say that natives of a region are completely free from possible infection: a middle-aged Turkish
Turkish people
Turkish people, also known as the "Turks" , are an ethnic group primarily living in Turkey and in the former lands of the Ottoman Empire where Turkish minorities had been established in Bulgaria, Cyprus, Bosnia and Herzegovina, Georgia, Greece, Kosovo, Macedonia, and Romania...

 lawyer
Lawyer
A lawyer, according to Black's Law Dictionary, is "a person learned in the law; as an attorney, counsel or solicitor; a person who is practicing law." Law is the system of rules of conduct established by the sovereign government of a society to correct wrongs, maintain the stability of political...

living in an urban area with water sanitized by the local government and with no travel history recently became Turkey’s first [en.wiktionary.org/wiki/autochthon autochthonous] case. This woman most likely received the infection from consuming some infected foodstuffs (possibly raspberries) that were not thoroughly washed before consumption. Thus, better health practices in the originating agricultural setting—such as ensuring produce is fully washed and kept away from human feces—and in the individual’s environment—taking an extra few seconds to wash that produce as well—would lead to a lower incidence of infection.
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