''Cyclospora cayetanensis'' is a
coccidian parasite that causes a
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
l disease called
cyclosporiasis in humans and possibly in other primates. Originally reported as a novel pathogen of probable coccidian nature in the 1980s
and described in the early 1990s,
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
Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, ...
and food-borne infections in developed nations.
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.
History
The first published report of ''Cyclospora cayetanensis'' in humans appears to be by Ashford (1979), who found unidentified ''
Isospora
''Isospora'' is a genus of internal parasites in the subclass Coccidia.
It is responsible for the condition isosporiasis, which causes acute, non-bloody diarrhoea in immunocompromised individuals.
Taxonomy
At least 248 species were originall ...
''-like
coccidia in the feces of three individuals in Papua, New Guinea. The photomicrographs in the paper reveal an organism morphologically identical to that seen now. 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
Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
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. 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.
Characterization
''Cyclospora cayetanensis'' is an
apicomplexa
The Apicomplexa (also called Apicomplexia) are a large phylum of parasitic alveolates. Most of them possess a unique form of organelle that comprises a type of non-photosynthetic plastid called an apicoplast, and an apical complex structure. Th ...
n, 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.
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
sporozoite
Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is ...
s; generally, two are observed per oocyst. After these sporozoites invade the epithelial cells, they undergo
merogony
Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
, 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
A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism.
In multicell ...
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
''Cryptosporidium parvum'' is one of several species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract.
Primary symptoms of ''C. parvum'' infection are acute, watery, and nonbloody diarrhea. ''C. parvum'' in ...
''—a closely related organism that causes a similar disease—since ''C. parvum'' oocysts are immediately infectious upon release from the host.
Symptoms
''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
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, fatigue, and low-grade
fever
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
", 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
Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the in ...
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
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
patients, such as those with
AIDS.
Human cyclosporiasis is clinically similar to
cryptosporidiosis
Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by '' Cryptosporidium'', a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tra ...
,
isosporiasis,
giardiasis
Giardiasis is a parasitic disease caused by ''Giardia duodenalis'' (also known as ''G. lamblia'' and ''G. intestinalis''). Infected individuals who experience symptoms (about 10% have no symptoms) may have diarrhea, abdominal pain, and weight los ...
and
microsporidiosis
Microsporidiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals ( HIV, for example). It results from different species of microsporidia, a group of microbial (unicellular) fungi.
In HI ...
because of the similar clinical features. Flu like syndrome with
myalgias and
arthralgia
Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication.
According to MeSH, ...
s may precede the onset of diarrhea. Fever is low grade and is unusual. There is presence of moderate to severe dehydration, compensatory
tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
, 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.
Risk factors
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.
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. 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.
Recognition
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
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(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.
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
__NOTOC__
Phase-contrast microscopy (PCM) is an optical microscopy technique that converts phase shifts in light passing through a transparent specimen to brightness changes in the image. Phase shifts themselves are invisible, but become visible ...
to check for the spherical oocysts described earlier, modified acid-fast staining to check for variable staining (from pale to red), and
autofluorescence
Autofluorescence is the natural emission of light by biological structures such as mitochondria and lysosomes when they have absorbed light, and is used to distinguish the light originating from artificially added fluorescent markers (fluorophores) ...
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%.
''C. cayetanensis'' has been confused with other protozoan infections in the past, most commonly being misidentified as ''
Cryptosporidium parvum
''Cryptosporidium parvum'' is one of several species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract.
Primary symptoms of ''C. parvum'' infection are acute, watery, and nonbloody diarrhea. ''C. parvum'' in ...
''. 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.
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
Multilocus sequence typing (MLST) is a technique in molecular biology for the typing of multiple loci, using DNA sequences of internal fragments of multiple housekeeping genes to characterize isolates of microbial species.
The first MLST scheme ...
based on
microsatellite markers
[ ] and
single nucleotide polymorphisms (SNPs) of nuclear markers.
[ ]
Treatment
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.
To date, the most effective drug for the treatment of the protozoan is a seven-day course of oral
trimethoprim-sulfamethoxazole
Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxaz ...
(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.
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
Kernicterus is a bilirubin-induced brain dysfunction. The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentratio ...
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.
No highly alternative antibiotic regimen has been discovered yet for patients who possess a sulfa-allergy.
Prevention
No vaccine against this pathogen is available. 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. 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.
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.
Outbreaks
U.S. foodborne outbreaks of cyclosporiasis: 2000–2014
Foodborne outbreaks of cyclosporiasis have been reported in the United States since the mid-1990s and 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 wer
summarizedpreviously, as were the major documented outbreaks i
an
Foodborne outbreaks during the 15-year period of 2000–2014 are summarized in 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 8 different 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.
Summary of U.S. foodborne outbreaks of cyclosporiasis, 2000–2014
* 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 additional details, see summary information about th
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 additional perspective, see summary information abou
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.
2013 United States outbreak
At least 285 people in 11 states had been affected as of July 26, 2013. The exact cause of the outbreak had not yet been identified according to the
U.S. Centers for Disease Control and Prevention (CDC).
The majority of cases were located in the
Midwest, with 138 reported cases in
Iowa
Iowa () is a state in the Midwestern region of the United States, bordered by the Mississippi River to the east and the Missouri River and Big Sioux River to the west. It is bordered by six states: Wisconsin to the northeast, Illinois to th ...
and 70 in
Nebraska
Nebraska () is a state in the Midwestern region of the United States. It is bordered by South Dakota to the north; Iowa to the east and Missouri to the southeast, both across the Missouri River; Kansas to the south; Colorado to the sout ...
. The other states affected are:
Texas
Texas (, ; Spanish: ''Texas'', ''Tejas'') is a state in the South Central region of the United States. At 268,596 square miles (695,662 km2), and with more than 29.1 million residents in 2020, it is the second-largest U.S. state by ...
,
Florida
Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...
,
Georgia
Georgia most commonly refers to:
* Georgia (country), a country in the Caucasus region of Eurasia
* Georgia (U.S. state), a state in the Southeast United States
Georgia may also refer to:
Places
Historical states and entities
* Related to the ...
,
Wisconsin
Wisconsin () is a state in the upper Midwestern United States. Wisconsin is the 25th-largest state by total area and the 20th-most populous. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake M ...
,
Connecticut
Connecticut () is the southernmost state in the New England region of the Northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, New York to the west, and Long Island Sound to the south. Its capita ...
,
Illinois
Illinois ( ) is a state in the Midwestern United States. Its largest metropolitan areas include the Chicago metropolitan area, and the Metro East section, of Greater St. Louis. Other smaller metropolitan areas include, Peoria and Rockf ...
,
Kansas
Kansas () is a state in the Midwestern United States. Its capital is Topeka, and its largest city is Wichita. Kansas is a landlocked state bordered by Nebraska to the north; Missouri to the east; Oklahoma to the south; and Colorado to th ...
,
Minnesota
Minnesota () is a state in the upper midwestern region of the United States. It is the 12th largest U.S. state in area and the 22nd most populous, with over 5.75 million residents. Minnesota is home to western prairies, now given over to ...
,
New Jersey
New Jersey is a state in the Mid-Atlantic and Northeastern regions of the United States. It is bordered on the north and east by the state of New York; on the east, southeast, and south by the Atlantic Ocean; on the west by the Delaware ...
, and
Ohio
Ohio () is a state in the Midwestern region of the United States. Of the fifty U.S. states, it is the 34th-largest by area, and with a population of nearly 11.8 million, is the seventh-most populous and tenth-most densely populated. The sta ...
.
As of July 29, 2013, the CDC reported 373 people in 15 states had been affected by the outbreak, and 21 patients from three states had been hospitalized, with no deaths reported. No food source had been identified, but health officials in Iowa—the state reporting the most cases—said they suspected imported vegetables.
On July 30, 2013, the
Nebraska Department of Health & Human Services and the Iowa Department of Health announced that a restaurant chain's packaged salad was the disease vector for the parasite. However, the CDC and the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) continued to assess information from other states to see if the findings applied to illnesses there.
In an August 1, 2013, update, the CDC reported 397 cases, while Iowa and Texas added another 22 more. This pushed the unofficial count to over 400 cases. Additionally, Louisiana reported its first case, bringing the total number of states affected to 16.
On August 3, 2013, CNN reported that the outbreak was traced to packaged salad served at Olive Garden and Red Lobster restaurants that was manufactured by
Taylor Farms de Mexico.
On August 15, 2013, the CDC reported nine more ''Cyclospora'' infections, raising its case count to 548. The number of affected states remained at 19, but the CDC said that not all cases were confirmed to be linked to an outbreak in Iowa and Nebraska traced to a contaminated salad mix from Mexico.
On August 19, 2013, the CDC reported 10 more ''Cyclospora'' cases, raising the unofficial count to over 600. Tennessee also reported its first case, bringing the number of states affect to 20. The CDC still cautions that whether cases in all of the states are related to outbreaks in Iowa and Nebraska is not clear.
As of August 27, 2013, the origin of the outbreak still remained a mystery. The FDA said it found no food safety violations at the Taylor Farms de Mexico salad plant that was linked to some of the illnesses.
2015 Texas outbreak
In an FDA statement, the CDC is quoted, "there is currently (in July 2015) another ongoing outbreak of cyclosporiasis in the United States in which both the Texas Department of State Health Services and the Wisconsin Department of Health Services and the Wisconsin Department of Agriculture, Trade and Consumer Protection have identified cilantro from the Mexican state of Puebla as a suspect vehicle with respect to separate illness clusters."
Last year, Texas had 200 cases, some of which were associated with cilantro from the Puebla region.
2016 Texas outbreak
Health officials said more than a dozen cases of cyclosporiasis had been confirmed in North Texas' four major counties and that the source was likely contaminated food.
The Texas Department of State Health Services said Wednesday the parasite was found in Dallas, Tarrant, Collin and Denton counties and that the origin may have been linked to a fresh produce item.
County officials told NBC 5 there were four cases recorded in Dallas County, three in Collin County, four in Denton County and seven in Tarrant County. The Denton County cases and at least four of the Tarrant County cases had recently traveled out of the country—calling into question the point of origin.
Across the state, there were currently 66 confirmed cases of cyclosporiasis—though the sources of infection were unconfirmed. For most people, the symptoms were not serious. "But for those who are very young and those who are older, or those who have a suppressed immune system, this illness can cause major problems," said Dr. Khang Tran, chief medical officer at The Medical Center of Plano.
In recent years, 2012–2015, cyclospora outbreaks were associated with fresh cilantro imported from Puebla, Mexico. Since the summer of 2015, the Food and Drug Administration has instituted ban on imports from that region between from April through August.
2018 Midwestern Del Monte vegetable outbreak
Del Monte recalled packaged Del Monte Fresh Produce vegetable trays, which contained broccoli, carrots, cauliflower, celery sticks, and dill dip, from certain retailers, including Kwik Trip and Peapod, according to the CDC. Residents in four states — Iowa, Michigan, Minnesota, and Wisconsin got sick from ''Cyclospora''.
2018 Midwestern McDonald's salad outbreak
McDonald's stopped selling salads
supplied by Fresh Express at some 3,000 locations across the country mostly in the
Midwest United States due to a multistate parasite outbreak that had sickened 551 people caused by ''Cyclospora''.
2020 Midwestern Fresh Express bagged garden salad outbreak
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. On June 27, 2020, Fresh Express announced a voluntary recall of over 91 Fresh Express and private label salad products.
IR=incidence rate per 100,000
* incidence rates are based on projected census data obtained from the DSHS Center for Health Statistics.
References
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{{Taxonbar, from=Q3008600
Conoidasida