Cyclosporiasis pathophysiology: Difference between revisions

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==Overview==
==Overview==
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.
''[[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, [[sporozoite]]s are released from [[oocyst]]s, 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]].


==Pathogenesis==
==Pathogenesis==
===Life Cycle===
===Life Cycle===
Unsporulated oocysts of ''Cyclospora cayetanensis'' are excreted from infected persons.  When freshly passed in stool, the oocyst is not infective (thus, direct fecal-oral transmission cannot occur, which differentiates Cyclospora from another important coccidian parasite, Cryptosporidium).  Under adequate temperatures (23-32ºC), these take about 7-15 days to sporulate, in order to become infectious.  After being ingested, from contaminated water and food, oocysts excyst to release elongated [[sporozoites]].  Sporozoites will then infect epithelial cells of the gastrointestinal tract, particularly those of the duodenum and jejunum. The sporozoites undergo asexual reproduction, originating meronts type I and II, which will then differentiate into gametocytes. These last will be fertilized to produce a zygote.<ref name="pmid10864257">{{cite journal| author=Eberhard ML, Ortega YR, Hanes DE, Nace EK, Do RQ, Robl MG et al.| title=Attempts to establish experimental Cyclospora cayetanensis infection in laboratory animals. | journal=J Parasitol | year= 2000 | volume= 86 | issue= 3 | pages= 577-82 | pmid=10864257 | doi=10.1645/0022-3395(2000)086[0577:ATEECC]2.0.CO;2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10864257  }} </ref><ref name="pmid20065331">{{cite journal| author=Ortega YR, Sanchez R| title=Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 1 | pages= 218-34 | pmid=20065331 | doi=10.1128/CMR.00026-09 | pmc=PMC2806662 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20065331  }} </ref>  Inside the cells, zygotes undergo asexual multiplication and sexual development to mature into oocysts, which will be shed in stool.<ref name=CDC>{{cite web | title = Cyclosporiasis | url = http://www.cdc.gov/parasites/cyclosporiasis/biology.html }}</ref>
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]].<ref name="pmid10864257">{{cite journal| author=Eberhard ML, Ortega YR, Hanes DE, Nace EK, Do RQ, Robl MG et al.| title=Attempts to establish experimental Cyclospora cayetanensis infection in laboratory animals. | journal=J Parasitol | year= 2000 | volume= 86 | issue= 3 | pages= 577-82 | pmid=10864257 | doi=10.1645/0022-3395(2000)086[0577:ATEECC]2.0.CO;2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10864257  }} </ref><ref name="pmid20065331">{{cite journal| author=Ortega YR, Sanchez R| title=Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 1 | pages= 218-34 | pmid=20065331 | doi=10.1128/CMR.00026-09 | pmc=PMC2806662 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20065331  }} </ref>  Inside cells, [[zygote]]s  undergo asexual reproduction and development to mature into [[oocysts]], which are shed in the stool.<ref name=CDC>{{cite web | title = Cyclosporiasis | url = http://www.cdc.gov/parasites/cyclosporiasis/biology.html }}</ref> ''[[C. cayetanensis]]'' [[oocyst]]s 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.<ref name="pmid10810327">{{cite journal| author=Di Gliullo AB, Cribari MS, Bava AJ, Cicconetti JS, Collazos R| title=Cyclospora cayetanensis in sputum and stool samples. | journal=Rev Inst Med Trop Sao Paulo | year= 2000 | volume= 42 | issue= 2 | pages= 115-7 | pmid=10810327 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10810327  }} </ref>
 
''C. cayetanensis'' oocysts have also been isolated from non gastrointestinal sites, namely from sputum of immunocompromised patients with HIV and concomitant TB.  This leads to hypothesis that ''C. cayetanensis'' may be an opportunistic pathogen.<ref name="pmid10810327">{{cite journal| author=Di Gliullo AB, Cribari MS, Bava AJ, Cicconetti JS, Collazos R| title=Cyclospora cayetanensis in sputum and stool samples. | journal=Rev Inst Med Trop Sao Paulo | year= 2000 | volume= 42 | issue= 2 | pages= 115-7 | pmid=10810327 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10810327  }} </ref>
 
 
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Thus far, C. cayetanensis infections have been identified only in humans. The role of other animal species as reservoirs or inter- mediary hosts has been examined, with conflicting results. Cyclo- spora oocysts have been found in feces of chickens (37, 62, 70), ducks (62, 197), and dogs (27, 37, 62, 194) collected in countries where Cyclospora is endemic (27, 62, 63). However, attempts to experimentally infect a variety of animals (63) and humans (5) have been unsuccessful. The presence of Cyclospora in stools from animals could be explained by eating or coprophagic habits of the surveyed animals. Nonetheless, it cannot yet be ruled out that animals may play a role in the dissemination of Cyclospora by contaminating water and food products. Two reports indicate that Cyclospora can be propagated in guinea pigs (191) and albino mice (162). These studies could not be reproduced, and further analyses are needed to determine the susceptibility of these ani- mals to infection by Cyclospora and their suitability as hosts or reservoirs of C. cayetanensis.
 
Insects, rotifers, and free-living nematodes could also play a role in the dissemination of oocysts, a phenomenon that has been described for Cryptosporidium (67, 74, 75, 90, 179) and other food-borne pathogens. The nematode Caenorhabditis elegans can ingest and excrete infectious bacteria (23, 98, 99) as well as Cryptosporidium parvum oocysts. Although the oocysts of Cyclospora are larger and may not be ingested by C. elegans, other, larger species of free-living nematodes could have a significant role in Cyclospora oocyst dissemination. Therefore, the role of free-living nematodes and other mechanical vectors in the contamination of produce and other food crops needs to be examined further (90).
 
Travel to rural areas and ingestion of contami- nated foods could be modes of infection. Accidental inhalation of oocysts has also been suggested (93)
 
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[[Image:Cyclosporiasis.gif|thumb|center|400 px|Life cycle of Cyclosporiasis<SMALL><SMALL>''[http://www.cdc.gov  - Center for Disease Control and Prevention(CDC)]''<ref name="CDC">{{Cite web | title = Center for Disease Control and Prevention (CDC) | url =  http://www.cdc.gov}}</ref></SMALL></SMALL>]]
[[Image:Cyclosporiasis.gif|thumb|center|400 px|Life cycle of Cyclosporiasis<SMALL><SMALL>''[http://www.cdc.gov  - Center for Disease Control and Prevention(CDC)]''<ref name="CDC">{{Cite web | title = Center for Disease Control and Prevention (CDC) | url =  http://www.cdc.gov}}</ref></SMALL></SMALL>]]


===Transmission===
===Transmission===
The protozoan lives out its lifecycle intracellularly within the host’s [[epithelial cell]]s and [[gastrointestinal tract]]. Infection is transmitted through the oral-fecal route, and begins when a person ingests oocysts in fecally contaminated food or water.  
''[[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.<ref name=CDC>{{cite web | title = Cyclosporiasis | url = http://www.cdc.gov/parasites/cyclosporiasis/biology.html }}</ref><ref name="pmid20065331">{{cite journal| author=Ortega YR, Sanchez R| title=Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 1 | pages= 218-34 | pmid=20065331 | doi=10.1128/CMR.00026-09 | pmc=PMC2806662 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20065331  }} </ref>
* Fresh produce and water can serve as vehicles for [[transmission]] and the sporulated oocysts are ingested (in contaminated food or water).
 
==Pathology==
''[[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.<ref name="pmid20065331">{{cite journal| author=Ortega YR, Sanchez R| title=Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 1 | pages= 218-34 | pmid=20065331 | doi=10.1128/CMR.00026-09 | pmc=PMC2806662 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20065331  }} </ref>  [[Histologic]] samples of [[small bowel]] of these patients demonstrate involvement of the [[lamina propria]] and [[neutrophil]]ic infiltration in some cases.  Cyclosporiasis may demonstrates evidence of [[chronic inflammation]], with [[plasma cells]] observed in mucosal samples of infected patients.<ref name="pmid8338291">{{cite journal| author=Connor BA, Shlim DR, Scholes JV, Rayburn JL, Reidy J, Rajah R| title=Pathologic changes in the small bowel in nine patients with diarrhea associated with a coccidia-like body. | journal=Ann Intern Med | year= 1993 | volume= 119 | issue= 5 | pages= 377-82 | pmid=8338291 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8338291  }} </ref>  Classically, [[immunocompromised]] patients are more prone to develop [[chronic inflammation]] of the [[gastrointestinal]] [[epithelium]].<ref name="pmid20065331">{{cite journal| author=Ortega YR, Sanchez R| title=Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 1 | pages= 218-34 | pmid=20065331 | doi=10.1128/CMR.00026-09 | pmc=PMC2806662 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20065331  }} </ref>


==Microscopic Pathology==
''Infected [[epithelial cells]] of the [[gastrointestinal]] tissue may demonstrate the following changes:''<ref name="pmid8338291">{{cite journal| author=Connor BA, Shlim DR, Scholes JV, Rayburn JL, Reidy J, Rajah R| title=Pathologic changes in the small bowel in nine patients with diarrhea associated with a coccidia-like body. | journal=Ann Intern Med | year= 1993 | volume= 119 | issue= 5 | pages= 377-82 | pmid=8338291 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8338291  }} </ref><ref name="pmid20065331">{{cite journal| author=Ortega YR, Sanchez R| title=Update on Cyclospora cayetanensis, a food-borne and waterborne parasite. | journal=Clin Microbiol Rev | year= 2010 | volume= 23 | issue= 1 | pages= 218-34 | pmid=20065331 | doi=10.1128/CMR.00026-09 | pmc=PMC2806662 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20065331  }} </ref>
*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


==References ==
==References ==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Infectious disease]]

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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]

Overview

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.

Pathogenesis

Life Cycle

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]

Life cycle of Cyclosporiasis- Center for Disease Control and Prevention(CDC)[3]

Transmission

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]

Pathology

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]

  • Increased length of crypts and increased mitosis
  • Shortened villi
  • Absence of parasitic vacuoles in biopsied samples

References

  1. Eberhard ML, Ortega YR, Hanes DE, Nace EK, Do RQ, Robl MG; et al. (2000). "Attempts to establish experimental Cyclospora cayetanensis infection in laboratory animals". J Parasitol. 86 (3): 577–82. doi:10.1645/0022-3395(2000)086[0577:ATEECC]2.0.CO;2. PMID 10864257.
  2. 2.0 2.1 2.2 2.3 2.4 Ortega YR, Sanchez R (2010). "Update on Cyclospora cayetanensis, a food-borne and waterborne parasite". Clin Microbiol Rev. 23 (1): 218–34. doi:10.1128/CMR.00026-09. PMC 2806662. PMID 20065331.
  3. 3.0 3.1 3.2 "Cyclosporiasis".
  4. Di Gliullo AB, Cribari MS, Bava AJ, Cicconetti JS, Collazos R (2000). "Cyclospora cayetanensis in sputum and stool samples". Rev Inst Med Trop Sao Paulo. 42 (2): 115–7. PMID 10810327.
  5. 5.0 5.1 Connor BA, Shlim DR, Scholes JV, Rayburn JL, Reidy J, Rajah R (1993). "Pathologic changes in the small bowel in nine patients with diarrhea associated with a coccidia-like body". Ann Intern Med. 119 (5): 377–82. PMID 8338291.

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