Whipworm infection pathophysiology: Difference between revisions

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==Overview==
==Overview==
[[Infection]] is acquired by the ingestion of [[Fertilised|embryonated]] eggs from [[Contamination|contaminated]] drinking water and food. The eggs once ingested hatch in the [[small intestine]], and the larvae enter the [[Intestinal mucosa|intestinal crypts]]. The larve migrate to the proximal [[colon]] and mature into adult worms. The females begin to [[Oviposition|oviposit]] 60 to 70 days after [[infection]] and shed between 3,000 and 20,000 eggs per day. [[Whipworm infection|Whipworm]] causes disease by [[Colon|colonic]] [[mucosal]] invasion by the adult worms and resulting in [[inflammation]] of the [[Colon|colonic]] [[mucosa]].
[[Infection]] is acquired by the ingestion of [[Fertilised|embryonated]] eggs from [[Contamination|contaminated]] drinking water and food. The eggs, once ingested, hatch in the [[small intestine]], and the larvae enter the [[Intestinal mucosa|intestinal crypts]]. The larve migrate to the proximal [[colon]] and mature into adult worms. The females begin to [[Oviposition|oviposit]] 60 to 70 days after [[infection]] and shed between 3,000 and 20,000 eggs per day. [[Whipworm infection|Whipworm]] causes disease by [[Colon|colonic]] [[Mucous membrane|mucosal]] invasion of the adult worms, resulting in [[inflammation]] of the [[Colon (anatomy)|colonic]] [[Mucous membrane|mucosa]].


==Pathophysiology==  
==Pathophysiology==  
===Life Cycle===
===Life cycle===
[[Image:Trichuris LifeCycle.gif|thumb|300px|center|Life Cycle of Trichiuris trichiura]]
[[Image:Trichuris LifeCycle.gif|thumb|300px|center|Life Cycle of Trichiuris trichiura -
Source: https://www.cdc.gov/]]


'''1.''' The eggs develop into a 2-cell stage.  
'''1.''' The eggs develop into a two-cell stage.  


'''2.''' The two cell stage then leads to an advanced cleavage stage.  
'''2.''' The two-cell stage then leads to an advanced cleavage stage.  


'''3.''' The eggs [[Fertilised|embryonate]].  
'''3.''' The eggs [[Fertilised|embryonate]].  
Line 25: Line 26:


===Pathogenesis===
===Pathogenesis===
*The eggs once ingested hatch in the [[small intestine]], and the larvae enter the [[Crypts of Lieberkühn|intestinal crypts]].<ref name="pmid16570666">{{cite journal| author=Elston DM| title=What's eating you? Trichuris trichiura (human whipworm). | journal=Cutis | year= 2006 | volume= 77 | issue= 2 | pages= 75-6 | pmid=16570666 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16570666  }} </ref><ref name="pmid15605023">{{cite journal| author=Elsayed S, Yilmaz A, Hershfield N| title=Trichuris trichiura worm infection. | journal=Gastrointest Endosc | year= 2004 | volume= 60 | issue= 6 | pages= 990-1 | pmid=15605023 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15605023  }} </ref>
*The eggs, once ingested, hatch in the [[small intestine]], and the larvae enter the [[Crypts of Lieberkühn|intestinal crypts]].<ref name="pmid16570666">{{cite journal| author=Elston DM| title=What's eating you? Trichuris trichiura (human whipworm). | journal=Cutis | year= 2006 | volume= 77 | issue= 2 | pages= 75-6 | pmid=16570666 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16570666  }} </ref><ref name="pmid15605023">{{cite journal| author=Elsayed S, Yilmaz A, Hershfield N| title=Trichuris trichiura worm infection. | journal=Gastrointest Endosc | year= 2004 | volume= 60 | issue= 6 | pages= 990-1 | pmid=15605023 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15605023  }} </ref>
*The larve migrate to the proximal [[colon]] and mature into adult worms.
*The larvae migrate to the proximal [[colon]] and mature into adult worms.
*The adult worms live in the [[cecum]] and [[ascending colon]] and attach themselves to the [[Colon|colonic mucosa]] with the anterior portions threaded into the [[mucosa]].  
*The adult worms live in the [[cecum]] and [[ascending colon]] and attach themselves to the [[Colon|colonic mucosa]] with their anterior portions threaded into the [[mucosa]].  
*The females begin to [[Oviposition|oviposit]] 60 to 70 days after infection and shed between 3,000 and 20,000 eggs per day.
*The females begin to [[Oviposition|oviposit]] 60 to 70 days after infection and shed between 3,000 and 20,000 eggs per day.
*[[Whipworm]] causes disease by [[Colon|colonic]] mucosal invasion of the adult worms and resulting in [[inflammation]] of the [[Colon|colonic]] [[mucosa]].<ref name="pmid16217807">{{cite journal| author=Tilney LG, Connelly PS, Guild GM, Vranich KA, Artis D| title=Adaptation of a nematode parasite to living within the mammalian epithelium. | journal=J Exp Zool A Comp Exp Biol | year= 2005 | volume= 303 | issue= 11 | pages= 927-45 | pmid=16217807 | doi=10.1002/jez.a.214 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16217807  }} </ref>
*[[Whipworm]] causes disease by [[Colon|colonic]] mucosal invasion of the adult worms, resulting in [[inflammation]] of the [[Colon|colonic]] [[mucosa]].<ref name="pmid16217807">{{cite journal| author=Tilney LG, Connelly PS, Guild GM, Vranich KA, Artis D| title=Adaptation of a nematode parasite to living within the mammalian epithelium. | journal=J Exp Zool A Comp Exp Biol | year= 2005 | volume= 303 | issue= 11 | pages= 927-45 | pmid=16217807 | doi=10.1002/jez.a.214 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16217807  }} </ref>


===Associated Conditions===
=== Molecular pathology ===
*[[Whipworm infection|Whipworm]] infection is frequently present in combination with [[Ascaris lumbricoides]], [[hookworm]] and [[Entamoeba histolytica]] infections.
{| class="wikitable"
|'''Secreted molecules by whipworm'''
|'''Role in pathogenesis'''
|-
|''[[Trichuris trichiura]]'' 47 (TT47)
|Forms pores in [[Cecum|cecal]] [[epithelial cells]]<ref name="pmid7991635">{{cite journal |vauthors=Drake L, Korchev Y, Bashford L, Djamgoz M, Wakelin D, Ashall F, Bundy D |title=The major secreted product of the whipworm, Trichuris, is a pore-forming protein |journal=Proc. Biol. Sci. |volume=257 |issue=1350 |pages=255–61 |year=1994 |pmid=7991635 |doi=10.1098/rspb.1994.0123 |url=}}</ref>
|-
|Excretory secretory products (ES products)
|Promote [[Th2]]/[[Regulatory T cells|Treg]] response that decreases [[Intestine|intestinal]] [[inflammation]]<ref name="pmid15978725">{{cite journal |vauthors=Parthasarathy G, Mansfield LS |title=Trichuris suis excretory secretory products (ESP) elicit interleukin-6 (IL-6) and IL-10 secretion from intestinal epithelial cells (IPEC-1) |journal=Vet. Parasitol. |volume=131 |issue=3-4 |pages=317–24 |year=2005 |pmid=15978725 |doi=10.1016/j.vetpar.2005.03.043 |url=}}</ref>
|-
|''[[Trichinella spiralis]]'' [[macrophage]] inhibitory factor (TsMIF)
|Inhibits migration of [[Macrophage|macrophages]] by inhibiting host [[macrophage]] inhibitory factor<ref name="pmid11439086">{{cite journal |vauthors=Tan TH, Edgerton SA, Kumari R, McAlister MS, Roe SM, Nagl S, Pearl LH, Selkirk ME, Bianco AE, Totty NF, Engwerda C, Gray CA, Meyer DJ, Rowe SM |title=Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis |journal=Biochem. J. |volume=357 |issue=Pt 2 |pages=373–83 |year=2001 |pmid=11439086 |pmc=1221963 |doi= |url=}}</ref>
|}


===Gross Pathology===
=== Host response ===
* Whipworm infection in humans can lead to rectal prolapse which may be visible grossly.<ref name="urlCDC - Trichuriasis">{{cite web |url=https://www.cdc.gov/parasites/whipworm/ |title=CDC - Trichuriasis |format= |work= |accessdate=}}</ref>
* Whipworm [[infection]] leads to a predominantly [[Th2 cell|T helper cell 2]] ([[Th2 cell|Th2]]) type [[immune response]], which is an [[antibody]]-based [[immune response]].<ref name="urlSoil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm - ScienceDirect">{{cite web |url=http://www.sciencedirect.com/science/article/pii/S0140673606686534?via%3Dihub |title=Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm - ScienceDirect |format= |work= |accessdate=}}</ref>
 
* Whipworm [[infection]] induces the production of [[cytokines]] ([[interleukin-4]], [[interleukin-5]], [[interleukin-10]], and [[interleukin-13]]), parasite-specific [[immunoglobulin]], and [[Immunoglobulin E|IgE]].<ref name="pmid8413664">{{cite journal |vauthors=Maizels RM, Bundy DA, Selkirk ME, Smith DF, Anderson RM |title=Immunological modulation and evasion by helminth parasites in human populations |journal=Nature |volume=365 |issue=6449 |pages=797–805 |year=1993 |pmid=8413664 |doi=10.1038/365797a0 |url=}}</ref>
* This leads to stimulation and [[proliferation]] of [[mast cells]], [[eosinophils]], and [[basophils]], which play effector roles during the [[infection]].
 
==Associated Conditions==
*[[Whipworm infection|Whipworm]] [[infection]] may present in combination with [[Ascaris lumbricoides|''Ascaris lumbricoides'']], [[Necator americanus|''Necator americanu''s]], and [[Entamoeba histolytica|''Entamoeba histolytica'']] infections.<ref name="pmid16679166">{{cite journal |vauthors=Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ |title=Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm |journal=Lancet |volume=367 |issue=9521 |pages=1521–32 |year=2006 |pmid=16679166 |doi=10.1016/S0140-6736(06)68653-4 |url=}}</ref>
*Whipworm [[infection]] can also exacerbate [[colitis]] caused by [[infection]] with ''[[Campylobacter jejuni]].''<ref name="pmid15054492">{{cite journal |vauthors=Shin JL, Gardiner GW, Deitel W, Kandel G |title=Does whipworm increase the pathogenicity of Campylobacter jejuni? A clinical correlate of an experimental observation |journal=Can. J. Gastroenterol. |volume=18 |issue=3 |pages=175–7 |year=2004 |pmid=15054492 |doi= |url=}}</ref>
 
==Gross Pathology==
* Whipworm infection in humans can lead to [[rectal prolapse]] which may be visible grossly.<ref name="urlCDC - Trichuriasis">{{cite web |url=https://www.cdc.gov/parasites/whipworm/ |title=CDC - Trichuriasis |format= |work= |accessdate=}}</ref>
[[Image:Rectal.jpg|200px|align right|Rectal prolapse in whipworm infection]]
[[Image:Rectal.jpg|200px|align right|Rectal prolapse in whipworm infection]]


===Microscopic Pathology===
==Microscopic Pathology==
*Microscopy of the colonic [[mucosal]] [[biopsy]] from the affected site will demonstrate [[eosinophilia]] and [[neutrophilia]].<ref name="pmid12236416">{{cite journal| author=Kaur G, Raj SM, Naing NN| title=Trichuriasis: localized inflammatory responses in the colon. | journal=Southeast Asian J Trop Med Public Health | year= 2002 | volume= 33 | issue= 2 | pages= 224-8 | pmid=12236416 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12236416  }} </ref>
 
*H&E stain of an infected [[Colon (anatomy)|colon]] may show one end of the worm embeded in the [[Hyperemic flow|hyperemic]] [[Mucous membrane|mucosa]] and other end freely movable within the [[Lumen (anatomy)|lumen]].<ref name="pmid19724702">{{cite journal |vauthors=Ok KS, Kim YS, Song JH, Lee JH, Ryu SH, Lee JH, Moon JS, Whang DH, Lee HK |title=Trichuris trichiura infection diagnosed by colonoscopy: case reports and review of literature |journal=Korean J. Parasitol. |volume=47 |issue=3 |pages=275–80 |year=2009 |pmid=19724702 |pmc=2735694 |doi=10.3347/kjp.2009.47.3.275 |url=}}</ref>
=== Colonic Biopsy ===
[[Image:Tri_worm.jpg|200px|align right|Black arrows showing worm embeded in mucosa of colon and white arrow showing one end of worm in lumen]]  
*Microscopy of the colonic [[mucosal]] [[biopsy]] from the affected site will demonstrate infiltration by [[eosinophils]] and [[neutrophils]].<ref name="pmid12236416">{{cite journal| author=Kaur G, Raj SM, Naing NN| title=Trichuriasis: localized inflammatory responses in the colon. | journal=Southeast Asian J Trop Med Public Health | year= 2002 | volume= 33 | issue= 2 | pages= 224-8 | pmid=12236416 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12236416  }} </ref>
*[[Hematoxylin and eosin stain|Hematoxylin and eosin (H&E) stain]] of an infected [[Colon (anatomy)|colon]] may show one end of the worm embedded in the [[Hyperemic flow|hyperemic]] [[Mucous membrane|mucosa]] and other end freely movable within the [[Lumen (anatomy)|lumen]].<ref name="pmid19724702">{{cite journal |vauthors=Ok KS, Kim YS, Song JH, Lee JH, Ryu SH, Lee JH, Moon JS, Whang DH, Lee HK |title=Trichuris trichiura infection diagnosed by colonoscopy: case reports and review of literature |journal=Korean J. Parasitol. |volume=47 |issue=3 |pages=275–80 |year=2009 |pmid=19724702 |pmc=2735694 |doi=10.3347/kjp.2009.47.3.275 |url=}}</ref>
[[Image:Tri_worm.jpg|200px|align right|Black arrows showing worm embeded in mucosa of colon and white arrow showing one end of worm in lumen]]
===Stool Examination===
*A [[stool examination]] for [[ova]] and [[parasites]] reveals the presence of [[whipworm]] eggs.
*The diagnostic characteristics are:<ref name="pmid166791662">{{cite journal |vauthors=Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ |title=Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm |journal=Lancet |volume=367 |issue=9521 |pages=1521–32 |year=2006 |pmid=16679166 |doi=10.1016/S0140-6736(06)68653-4 |url=}}</ref>
**A typical barrel shape
**Two polar plugs that are unstained
**Size: 50 to 54 µm by 22 to 23 µm
**The external layer of the shell of the egg is yellow-brown (in contrast to the clear polar plugs).
[[Image:Trichuris eggA.jpg|thumb|left|''T. trichiura'' egg]]
<br clear="left" />


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 00:45, 30 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2], Syed Hassan A. Kazmi BSc, MD [3]

Overview

Infection is acquired by the ingestion of embryonated eggs from contaminated drinking water and food. The eggs, once ingested, hatch in the small intestine, and the larvae enter the intestinal crypts. The larve migrate to the proximal colon and mature into adult worms. The females begin to oviposit 60 to 70 days after infection and shed between 3,000 and 20,000 eggs per day. Whipworm causes disease by colonic mucosal invasion of the adult worms, resulting in inflammation of the colonic mucosa.

Pathophysiology

Life cycle

Life Cycle of Trichiuris trichiura - Source: https://www.cdc.gov/

1. The eggs develop into a two-cell stage.

2. The two-cell stage then leads to an advanced cleavage stage.

3. The eggs embryonate.

4. Eggs become infective in 15 to 30 days.

5. Mature adult worms travel in the colon.

6. The adult worms (approximately 4 cm in length) live in the cecum and ascending colon. The life span of the adult worm is approximately 1 year.

Transmission

  • Whipworm infection is acquired by the ingestion of embryonated eggs from contaminated drinking water and food.

Pathogenesis

Molecular pathology

Secreted molecules by whipworm Role in pathogenesis
Trichuris trichiura 47 (TT47) Forms pores in cecal epithelial cells[4]
Excretory secretory products (ES products) Promote Th2/Treg response that decreases intestinal inflammation[5]
Trichinella spiralis macrophage inhibitory factor (TsMIF) Inhibits migration of macrophages by inhibiting host macrophage inhibitory factor[6]

Host response

Associated Conditions

Gross Pathology

Rectal prolapse in whipworm infection

Microscopic Pathology

Colonic Biopsy

Black arrows showing worm embeded in mucosa of colon and white arrow showing one end of worm in lumen

Stool Examination

  • A stool examination for ova and parasites reveals the presence of whipworm eggs.
  • The diagnostic characteristics are:[14]
    • A typical barrel shape
    • Two polar plugs that are unstained
    • Size: 50 to 54 µm by 22 to 23 µm
    • The external layer of the shell of the egg is yellow-brown (in contrast to the clear polar plugs).
T. trichiura egg


References

  1. ↑ Elston DM (2006). "What's eating you? Trichuris trichiura (human whipworm)". Cutis. 77 (2): 75–6. PMID 16570666.
  2. ↑ Elsayed S, Yilmaz A, Hershfield N (2004). "Trichuris trichiura worm infection". Gastrointest Endosc. 60 (6): 990–1. PMID 15605023.
  3. ↑ Tilney LG, Connelly PS, Guild GM, Vranich KA, Artis D (2005). "Adaptation of a nematode parasite to living within the mammalian epithelium". J Exp Zool A Comp Exp Biol. 303 (11): 927–45. doi:10.1002/jez.a.214. PMID 16217807.
  4. ↑ Drake L, Korchev Y, Bashford L, Djamgoz M, Wakelin D, Ashall F, Bundy D (1994). "The major secreted product of the whipworm, Trichuris, is a pore-forming protein". Proc. Biol. Sci. 257 (1350): 255–61. doi:10.1098/rspb.1994.0123. PMID 7991635.
  5. ↑ Parthasarathy G, Mansfield LS (2005). "Trichuris suis excretory secretory products (ESP) elicit interleukin-6 (IL-6) and IL-10 secretion from intestinal epithelial cells (IPEC-1)". Vet. Parasitol. 131 (3–4): 317–24. doi:10.1016/j.vetpar.2005.03.043. PMID 15978725.
  6. ↑ Tan TH, Edgerton SA, Kumari R, McAlister MS, Roe SM, Nagl S, Pearl LH, Selkirk ME, Bianco AE, Totty NF, Engwerda C, Gray CA, Meyer DJ, Rowe SM (2001). "Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis". Biochem. J. 357 (Pt 2): 373–83. PMC 1221963. PMID 11439086.
  7. ↑ "Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm - ScienceDirect".
  8. ↑ Maizels RM, Bundy DA, Selkirk ME, Smith DF, Anderson RM (1993). "Immunological modulation and evasion by helminth parasites in human populations". Nature. 365 (6449): 797–805. doi:10.1038/365797a0. PMID 8413664.
  9. ↑ Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ (2006). "Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm". Lancet. 367 (9521): 1521–32. doi:10.1016/S0140-6736(06)68653-4. PMID 16679166.
  10. ↑ Shin JL, Gardiner GW, Deitel W, Kandel G (2004). "Does whipworm increase the pathogenicity of Campylobacter jejuni? A clinical correlate of an experimental observation". Can. J. Gastroenterol. 18 (3): 175–7. PMID 15054492.
  11. ↑ "CDC - Trichuriasis".
  12. ↑ Kaur G, Raj SM, Naing NN (2002). "Trichuriasis: localized inflammatory responses in the colon". Southeast Asian J Trop Med Public Health. 33 (2): 224–8. PMID 12236416.
  13. ↑ Ok KS, Kim YS, Song JH, Lee JH, Ryu SH, Lee JH, Moon JS, Whang DH, Lee HK (2009). "Trichuris trichiura infection diagnosed by colonoscopy: case reports and review of literature". Korean J. Parasitol. 47 (3): 275–80. doi:10.3347/kjp.2009.47.3.275. PMC 2735694. PMID 19724702.
  14. ↑ Bethony J, Brooker S, Albonico M, Geiger SM, Loukas A, Diemert D, Hotez PJ (2006). "Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm". Lancet. 367 (9521): 1521–32. doi:10.1016/S0140-6736(06)68653-4. PMID 16679166.

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