Cyclosporiasis

Cyclosporiasis
Other names: cyclosporosis
Cyclospora cayetanensis
SpecialtyInfectious disease
SymptomsWatery diarrhea, cramping, nausea
CausesCyclospora cayetanensis
Diagnostic methodPCR tests
TreatmentTrimethoprim/sulfamethoxazole

Cyclosporiasis is a disease caused by infection with Cyclospora cayetanensis, a pathogenic protozoan transmitted by feces or feces-contaminated food and water.[1] Cyclosporiasis 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 food-borne infections in developed nations.[2]

It is not spread from person to person, but can be a hazard for travelers or tourists as a cause of traveler's diarrhea.[3][4][5]

Signs and symptoms

The clinical presentation of Cyclosporiasis is as follows, C. cayetanensis causes gastroenteritis, with the extent of the illness varying based on age, condition of the host, and size of the infectious dose. [6]

Symptoms include "watery diarrhea, loss of appetite, weight loss, abdominal bloating and cramping, nausea, fatigue, and fever", though this can be augmented in more severe cases by vomiting, weight loss, and diarrhea. [6][5][7]

Cause

Presence of three uniformly stained Cyclospora cayetanensis oocysts

Cyclosporiasis primarily affects humans and other primates. When an oocyst of Cyclospora cayetanensis enters the small intestine, it invades the mucosa, where it incubates for about one week. After incubation, the infected person begins to experience severe watery diarrhea, bloating, fever, stomach cramps, and muscle aches.[8][9]

The parasite particularly affects the jejunum of the small intestine. Of nine patients in Nepal who were diagnosed with cyclosporiasis, all had inflammation of the lamina propria along with an increase of plasma in the lamina propria. Oocysts were also observed in duodenal aspirates.[10]

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 summer.[11][2][12]

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.[13]

Diagnosis

Methods have 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 of C. cayetanensis DNA. 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.[14][15][7]

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.[14][7]

Prevention

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, 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; 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.[2]

Treatment

Trimethoprim and sulfamethoxazole

Most people who have healthy immune systems will recover without treatment, however, 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, people who are in poor health or who have weakened immune systems may be at higher risk for severe or prolonged illness.[18]

The infection is often treated with trimethoprim/sulfamethoxazole, also known as Bactrim or co-trimoxazole, because traditional anti-protozoal drugs are not sufficient.[19]

Epidemiology

Outbreaks

Although it was initially thought that Cyclospora was confined to tropical and subtropical regions, occurrences of cyclosporiasis are becoming more frequent in North America. According to the Centers for Disease Control and Prevention, there have been 11 documented cyclosporiasis outbreaks in the U.S. and Canada since the 1990s. The CDC also recorded 1,110 laboratory-confirmed sporadic instances of cyclosporiasis.[20]

Between June and August 2013, multiple independent outbreaks of the disease in the U.S. sickened at least 631 people across 25 states.[21][22] Investigations later identified a bagged salad mixture as the cause of an outbreak in Iowa and Nebraska.[23]

In 2015, the CDC was notified of 546 persons with confirmed cyclosporiasis infection across 31 states. Cluster investigations in Texas, where the greatest number of infections was reported, indicated that contaminated cilantro was the culprit.[24] During July 21–August 8, 2017, the Texas Department of State Health Services (DSHS) was notified of 20 cases of cyclosporiasis among persons who dined at a Mediterranean-style restaurant chain (chain A) in the Houston area.[25]On July 31, 2018, the United States Department of Agriculture (USDA) issued a public health alert for certain beef, pork and poultry salad and wrap products potentially contaminated with Cyclospora,[26] the contamination came from the chopped romaine lettuce used in these products.

In June 2020, the CDC and other regulatory bodies began investigating an outbreak of Cyclosporiasis in the Midwestern United States linked to bagged salad mix.[27] On June 27, 2020, Fresh Express announced a voluntary recall of over 91 Fresh Express and private label salad products.[28]

Summary of U.S. foodborne outbreaks of cyclosporiasis, 2000–2014 [29]

Nebraska, U.S. Bagged salad mixture was cause of outbreak in Nebraska[30] (and Iowa) 2013
September 2013, U.S. states reporting Cyclospora infections
Year(s)*Month(s)*Jurisdiction(s)*No. of cases†Food vehicle and source, if identified‡
2000MayGeorgia19Raspberries and/or blackberries (suspected)
2000JunePennsylvania54Raspberries
2001January–FebruaryFlorida39
2001JanuaryNew York City3
2001–02December–JanuaryVermont22Raspberries (likely)
2002April–MayMassachusetts8
2002JuneNew York14
2004FebruaryTexas38
2004FebruaryIllinois57Basil (likely)
2004MayTennessee12
2004May–JunePennsylvania96Snow peas from Guatemala
2005March–MayFlorida582 ¶Basil from Peru
2005MaySouth Carolina6
2005AprilMassachusetts58
2005MayMassachusetts16
2005JuneConnecticut30Basil (suspected)
2006JuneMinnesota14
2006JuneNew York20
2006JulyGeorgia3
2008MarchWisconsin4Sugar snap peas (likely)
2008JulyCalifornia45 ¶Raspberries and/or blackberries (likely)
2009JuneDistrict of Columbia34
2011JuneFlorida12
2011JulyGeorgia100
2012June–JulyTexas16
2013**JuneIowa and Nebraska161Bagged salad mix from Mexico
2013**June–JulyTexas38Cilantro from Mexico
2013JulyWisconsin8Berry salad (suspected)
2014JuneMichigan14
2014††June–JulyTexas26Cilantro from Mexico
2014JulySouth Carolina13

(*)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.
(**)For the purposes of this table, the exposure month(s) and case counts are limited to those explicitly linked in the investigations to the food item specified in the last column.
† The case counts include laboratory-confirmed and probable cases of cyclosporiasis. By definition, each outbreak included at least two linked cases, at least one of which was laboratory confirmed.
‡ A food vehicle is specified only if a single ingredient or commodity was identified in an outbreak investigation.
¶ Cases that occurred in Canadian travelers to the United States were not included.
†† For the purposes of this table, the exposure months and the case count for the outbreak in Texas are limited to those explicitly linked in the investigations to the food item specified in the last column

History

The first recorded cases of cyclosporiasis in humans were as recent 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, and thus can be easily overlooked.[31]

In 2007, Indian researchers published a case report that found an association between Cyclospora infection and Bell's palsy. This was the first reported case of Bell’s palsy following chronic Cyclospora infection.[32] In addition to other extra-intestinal reports, cyclosporiasis might be involved in either reversible neuronal damage or other unknown mechanisms that lead to Guillain-Barré syndrome[15]

In 2010, a report of Cyclospora transmission via swimming in the Kathmandu Valley was published in the Journal of Institute of Medicine.[33] The researchers found that openly defecated human stool samples around the swimmer's living quarters and near the swimming pool were positive for Cyclospora. However, they did not find the parasite in dog stool, bird stool, cattle dung, vegetable samples, or water samples. They concluded that pool water contaminated via environmental pollution might have caused the infection, as the parasite can resist chlorination in water.[34]

Cyclosporiasis infections have been well reported in Nepal. In one study, Tirth Raj Ghimire, Purna Nath Mishra, and Jeevan Bahadur Sherchan collected samples of vegetables, sewage, and water from ponds, rivers, wells, and municipal taps in the Kathmandu Valley from 2002 to 2004.[35] 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.[36]

Cyclosporiasis and AIDS

HIV-1 budding

The beginning of the AIDS epidemic in the early 1980s, cyclosporiasis was identified as one of the most important opportunistic infections among AIDS patients.[2]In 2005, Ghimire and Mishra reported a case of cyclosporiasis in a patient with low hemoglobin and suggested that this coccidian might be involved in reducing hemoglobin due to lack of immune system.[37]

In 2006, their groups published a paper about the role of cyclosporiasis in HIV/AIDS patients and non-HIV/AIDS patients in the Kathmandu Valley.[38]In 2008, Indian researchers published a report about the epidemiology of Cyclospora in HIV/AIDS patients in Kathmandu.[39] They examined samples of soil, river water, sewage, chicken stool, dog stool, and stool in the streets, and found them positive for Cyclospora. They also evaluated several risk factors for cyclosporiasis in AIDS patients.[39]

When infected with cyclospora, AIDS individuals tend to have greater weight loss than non-AIDS individuals due to diarrhea[40]


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