Giardiasis: Difference between revisions
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| frequency = Up to 7% (developed world), up to 30% (developing world)<ref name=BMJ2016/> |
| frequency = Up to 7% (developed world), up to 30% (developing world)<ref name=BMJ2016/> |
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'''Giardiasis''' is a [[parasitic disease]] caused by ''[[Giardia duodenalis]]'' (also known as ''G. lamblia'' and ''G. intestinalis'').<ref name="Esch2013">{{cite journal | vauthors = Esch KJ, Petersen CA | title = Transmission and epidemiology of zoonotic protozoal diseases of companion animals | journal = Clinical Microbiology Reviews | volume = 26 | issue = 1 | pages = 58–85 | date = January 2013 | pmid = 23297259 | pmc = 3553666 | doi = 10.1128/CMR.00067-12 }}</ref> Infected individuals who experience symptoms (about 10% have no symptoms) may have [[diarrhea]], [[abdominal pain]], and [[weight loss]].<ref name=BMJ2016/> Less common symptoms include vomiting and [[blood in the stool]].<ref name=BMJ2016/> Symptoms usually begin |
'''Giardiasis''' is a [[parasitic disease]] caused by ''[[Giardia duodenalis]]'' (also known as ''G. lamblia'' and ''G. intestinalis'').<ref name="Esch2013">{{cite journal | vauthors = Esch KJ, Petersen CA | title = Transmission and epidemiology of zoonotic protozoal diseases of companion animals | journal = Clinical Microbiology Reviews | volume = 26 | issue = 1 | pages = 58–85 | date = January 2013 | pmid = 23297259 | pmc = 3553666 | doi = 10.1128/CMR.00067-12 }}</ref> Infected individuals who experience symptoms (about 10% have no symptoms) may have [[diarrhea|diarrhoea]], [[abdominal pain]], and [[weight loss]].<ref name=BMJ2016/> Less common symptoms include vomiting and [[blood in the stool]].<ref name=BMJ2016/> Symptoms usually begin one to three weeks after exposure and, without treatment, may last two to six weeks or longer.<ref name=CDCSymptoms/> |
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Giardiasis usually spreads when ''Giardia duodenalis'' cysts within [[feces]] contaminate food or water that is later consumed orally.<ref name=BMJ2016/> The disease can also spread between people and through other animals.<ref name=BMJ2016/> Cysts may survive for nearly three months in cold water.<ref name=BMJ2016/> Giardiasis is diagnosed via stool tests.<ref name=BMJ2016/> |
Giardiasis usually spreads when ''Giardia duodenalis'' cysts within [[feces|faeces]] contaminate food or water that is later consumed orally.<ref name=BMJ2016/> The disease can also spread between people and through other animals.<ref name=BMJ2016/> Cysts may survive for nearly three months in cold water.<ref name=BMJ2016/> Giardiasis is diagnosed via stool tests.<ref name=BMJ2016/> |
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Prevention may be improved through proper [[hygiene]] practices.<ref name="BMJ2016" /> Asymptomatic cases often do not need treatment.<ref name="BMJ2016" /> When symptoms are present, treatment is typically provided with either [[tinidazole]] or [[metronidazole]].<ref name=BMJ2016/> Infection may cause a person to become [[lactose intolerant]], so it is recommended to temporarily avoid lactose following an infection.<ref name=BMJ2016/> [[Antimicrobial resistance|Resistance]] to treatment may occur in some patients.<ref name=BMJ2016/> |
Prevention may be improved through proper [[hygiene]] practices.<ref name="BMJ2016" /> Asymptomatic cases often do not need treatment.<ref name="BMJ2016" /> When symptoms are present, treatment is typically provided with either [[tinidazole]] or [[metronidazole]].<ref name=BMJ2016/> Infection may cause a person to become [[lactose intolerant]], so it is recommended to temporarily avoid lactose following an infection.<ref name=BMJ2016/> [[Antimicrobial resistance|Resistance]] to treatment may occur in some patients.<ref name=BMJ2016/> |
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==Signs and symptoms== |
==Signs and symptoms== |
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Symptoms vary from none to severe |
Symptoms vary from none to severe diarrhoea with poor absorption of nutrients.<ref name=CDC_Giardiasis/> The cause of this wide range in severity of symptoms is not fully known but the intestinal flora of the infected host may play a role.<ref name=Cot2011>{{cite journal | vauthors = Cotton JA, Beatty JK, Buret AG | title = Host parasite interactions and pathophysiology in Giardia infections | journal = International Journal for Parasitology | volume = 41 | issue = 9 | pages = 925–33 | date = August 2011 | pmid = 21683702 | doi = 10.1016/j.ijpara.2011.05.002 }}</ref><ref name=":4">{{cite journal | vauthors = Einarsson E, Ma'ayeh S, Svärd SG | title = An up-date on Giardia and giardiasis | journal = Current Opinion in Microbiology | volume = 34 | pages = 47–52 | date = December 2016 | pmid = 27501461 | doi = 10.1016/j.mib.2016.07.019 }}</ref> Diarrhoea is less likely to occur in people from developing countries.<ref name=Cot2011 /> |
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Symptoms typically develop 9–15 days after exposure,<ref name="Barry2013" /> but may occur as early as one day.<ref name="CDC_Giardiasis">{{cite web |title=Giardiasis |url=https://www.cdc.gov/dpdx/giardiasis/|website=cdc.gov |date=December 9, 2017 |access-date=27 March 2022 |url-status=live|archive-url= https://web.archive.org/web/20210414044832/https://www.cdc.gov/dpdx/giardiasis/ |archive-date=April 14, 2021}}</ref> The most common and prominent symptom is chronic |
Symptoms typically develop 9–15 days after exposure,<ref name="Barry2013" /> but may occur as early as one day.<ref name="CDC_Giardiasis">{{cite web |title=Giardiasis |url=https://www.cdc.gov/dpdx/giardiasis/|website=cdc.gov |date=December 9, 2017 |access-date=27 March 2022 |url-status=live|archive-url= https://web.archive.org/web/20210414044832/https://www.cdc.gov/dpdx/giardiasis/ |archive-date=April 14, 2021}}</ref> The most common and prominent symptom is chronic diarrhoea, which can occur for weeks or months if untreated.<ref name=PD6>{{cite book |chapter-url=http://www.parasiteswithoutborders.com/parasitic-diseases-6th-edition/ |access-date=11 July 2018 |title=Parasitic Diseases |edition=6 |vauthors=Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA |publisher=Parasites Without Borders |location=NY |chapter=III. Eukaryotic Parasites |pages=11–17 |archive-date=7 March 2020 |archive-url=https://web.archive.org/web/20200307144527/http://www.parasiteswithoutborders.com/parasitic-diseases-6th-edition |url-status=dead }}</ref><ref name=Robertson2010>{{cite journal | vauthors = Robertson LJ, Hanevik K, Escobedo AA, Mørch K, Langeland N | title = Giardiasis--why do the symptoms sometimes never stop? | journal = Trends in Parasitology | volume = 26 | issue = 2 | pages = 75–82 | date = February 2010 | pmid = 20056486 | doi = 10.1016/j.pt.2009.11.010 }}</ref> Diarrhoea is often greasy and foul-smelling, with a tendency to float.<ref name=PD6/><ref name=CDCSymptoms>{{cite web |url=https://www.cdc.gov/parasites/giardia/illness.html |title=Giardia. Illness and symptoms |website=CDC |date=26 February 2021 |access-date=27 March 2022}}</ref> This characteristic diarrhoea is often accompanied by a number of other symptoms, including [[flatulence|gas]], abdominal cramps, and nausea or vomiting.<ref name="PD6" /><ref name=CDCSymptoms/> Some people also experience symptoms outside of the gastrointestinal tract, such as itchy skin, [[hives]], and swelling of the eyes and joints, although these are less common.<ref name=CDCSymptoms/> Fever occurs in only about 15% of infected people,<ref>{{Cite book |title=Tropical infectious diseases : principles, pathogens and practice |url=https://archive.org/details/tropicalinfectio00mdri_338 |url-access=limited|date=2011|publisher=Saunders/Elsevier|author1=Guerrant, Richard L. |author2=Walker, David H. |author3=Weller, Peter F. |isbn=9781437737776|edition=3rd|location=Edinburgh|pages=[https://archive.org/details/tropicalinfectio00mdri_338/page/n647 623]|oclc=722800379}}</ref> despite the nickname "beaver fever".<ref name=NYSDOH/> |
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Prolonged disease is often |
Prolonged disease is often characterised by diarrhoea and [[Malabsorption|malabsorption of nutrients]] in the intestine.<ref name=PD6/> This malabsorption causes [[steatorrhea|fatty stools]], substantial weight loss, and [[fatigue]].<ref name=PD6/> Additionally, those with giardiasis often have difficulty absorbing [[lactose]], [[vitamin A]], [[folate]], and [[Vitamin B12 deficiency|vitamin B<sub>12</sub>]].<ref name=Robertson2010/><ref name=CDCSymptoms/> In children, prolonged giardiasis can cause [[failure to thrive]] and may impair mental development.<ref name="PD6" /><ref name=Robertson2010/> Symptomatic infections are well recognised as causing [[lactose intolerance]],<ref name="pmid2614615">{{cite journal | vauthors = Pettoello Mantovani M, Guandalini S, Ecuba P, Corvino C, di Martino L | s2cid = 32254397 | title = Lactose malabsorption in children with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 9 | issue = 3 | pages = 295–300 | date = October 1989 | pmid = 2614615 | doi = 10.1097/00005176-198910000-00006 | doi-access = free }}</ref> which, though usually temporary, may become permanent.<ref name="pmid1174208">{{cite journal | vauthors = Wolfe MS | title = Giardiasis | journal = JAMA | volume = 233 | issue = 13 | pages = 1362–5 | date = September 1975 | pmid = 1174208 | doi = 10.1001/jama.233.13.1362 }}</ref><ref name="pmid3430245">{{cite journal | vauthors = Vega-Franco L, Meza C, Romero JL, Alanis SE, Meijerink J | s2cid = 20733304 | title = Breath hydrogen test in children with giardiasis | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 6 | issue = 3 | pages = 365–8 | year = 1987 | pmid = 3430245 | doi = 10.1097/00005176-198705000-00010 | doi-access = free }}</ref> |
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==Cause== |
==Cause== |
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{{multiple image |
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| image1 = Infectiology - Giarda intestinalis - Cyst -- Smart-Servier.png |
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| alt1 = Cyst of Giarda intestinalis |
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| image2 = Infectiology - Giarda intestinalis - Trophozoite -- Smart-Servier.png |
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| alt2 = Trophozoite of Giarda intestinalis |
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| footer = Cyst (left) and [[trophozoite]] (right) of ''Giarda intestinalis'' |
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}} |
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Giardiasis is caused by the [[protozoan]] ''[[Giardia lamblia|Giardia duodenalis]]''.<ref name=Auer2012/> The infection occurs in many animals, including beavers, other rodents, cows, and sheep.<ref name=Auer2012/> Animals are believed to play a role in keeping infections present in an environment.<ref name=Auer2012/> |
Giardiasis is caused by the [[protozoan]] ''[[Giardia lamblia|Giardia duodenalis]]''.<ref name=Auer2012/> The infection occurs in many animals, including beavers, other rodents, cows, and sheep.<ref name=Auer2012/> Animals are believed to play a role in keeping infections present in an environment.<ref name=Auer2012/> |
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''G. duodenalis'' has been sub-classified into eight genetic assemblages (designated A–H).<ref name="Heyworth2016" /> Genotyping of ''G. duodenalis'' isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main and possibly only ''G. duodenalis'' assemblages that infect humans.<ref name="Heyworth2016">{{cite journal | vauthors = Heyworth MF | title = Giardia duodenalis genetic assemblages and hosts | journal = Parasite | volume = 23 | pages = 13 | year = 2016 | pmid = 26984116 | pmc = 4794627 | doi = 10.1051/parasite/2016013 | url = https://www.parasite-journal.org/articles/parasite/full_html/2016/01/parasite150104/parasite150104.html| url-status = live | archive-url = https://web.archive.org/web/20170910163601/https://www.parasite-journal.org/articles/parasite/full_html/2016/01/parasite150104/parasite150104.html | archive-date = 2017-09-10 }} {{open access}}</ref><ref>{{cite journal | vauthors = Lalle M, Hanevik K | title = Treatment-refractory giardiasis: challenges and solutions | language = en | journal = Infection and Drug Resistance | volume = 11 | pages = 1921–1933 | date = 2018-10-24 | pmid = 30498364 | pmc = 6207226 | doi = 10.2147/idr.s141468 }}</ref> |
''G. duodenalis'' has been sub-classified into eight genetic assemblages (designated A–H).<ref name="Heyworth2016" /> Genotyping of ''G. duodenalis'' isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main and possibly only ''G. duodenalis'' assemblages that infect humans.<ref name="Heyworth2016">{{cite journal | vauthors = Heyworth MF | title = Giardia duodenalis genetic assemblages and hosts | journal = Parasite | volume = 23 | pages = 13 | year = 2016 | pmid = 26984116 | pmc = 4794627 | doi = 10.1051/parasite/2016013 | url = https://www.parasite-journal.org/articles/parasite/full_html/2016/01/parasite150104/parasite150104.html| url-status = live | archive-url = https://web.archive.org/web/20170910163601/https://www.parasite-journal.org/articles/parasite/full_html/2016/01/parasite150104/parasite150104.html | archive-date = 2017-09-10 }} {{open access}}</ref><ref>{{cite journal | vauthors = Lalle M, Hanevik K | title = Treatment-refractory giardiasis: challenges and solutions | language = en | journal = Infection and Drug Resistance | volume = 11 | pages = 1921–1933 | date = 2018-10-24 | pmid = 30498364 | pmc = 6207226 | doi = 10.2147/idr.s141468 | doi-access = free }}</ref> |
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===Risk factors=== |
===Risk factors=== |
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* People in childcare settings |
* People in childcare settings |
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* People who are in close contact with someone who has the disease |
* People who are in close contact with someone who has the disease |
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* |
* Travellers within areas that have poor sanitation |
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* People who have contact with |
* People who have contact with faeces during sexual activity |
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* Backpackers or campers who drink untreated water from springs, lakes, or rivers |
* Backpackers or campers who drink untreated water from springs, lakes, or rivers |
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* Swimmers who swallow water from swimming pools, hot tubs, interactive fountains, or untreated recreational water from springs, lakes, or rivers |
* Swimmers who swallow water from swimming pools, hot tubs, interactive fountains, or untreated recreational water from springs, lakes, or rivers |
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* People who get their household water from a shallow well |
* People who get their household water from a shallow well |
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* People with weakened immune systems |
* People with weakened immune systems |
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* People who have contact with infected animals or animal environments contaminated with |
* People who have contact with infected animals or animal environments contaminated with faeces |
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Factors that increase infection risk for people from developed countries include changing diapers, consuming raw food, owning a dog, and travelling in the [[developing world]].<ref name=BMJ2016/> However, 75% of infections in the United Kingdom are acquired in the UK, not through travel elsewhere.<ref name=BMJ2016/> In the United States, giardiasis occurs more often in summer, which is believed to be due to a greater amount of time spent on outdoor activities and |
Factors that increase infection risk for people from developed countries include changing nappies/diapers, consuming raw food, owning a dog, and travelling in the [[developing world]].<ref name=BMJ2016/> However, 75% of infections in the United Kingdom are acquired in the UK, not through travel elsewhere.<ref name=BMJ2016/> In the United States, giardiasis occurs more often in summer, which is believed to be due to a greater amount of time spent on outdoor activities and travelling in the wilderness.<ref name=Auer2012/> |
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===Transmission=== |
===Transmission=== |
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Giardiasis is transmitted via the [[fecal-oral route]] with the ingestion of [[Microbial cyst|cyst]]s.<ref name="Barry2013">{{cite journal | vauthors = Barry MA, Weatherhead JE, Hotez PJ, Woc-Colburn L | title = Childhood parasitic infections endemic to the United States | journal = Pediatric Clinics of North America | volume = 60 | issue = 2 | pages = 471–85 | date = April 2013 | pmid = 23481112 | doi = 10.1016/j.pcl.2012.12.011 }}</ref> Primary routes are personal contact and contaminated water and food.<ref name="Barry2013"/> The cysts can stay infectious for up to three months in cold water.<ref name=Auer2012/> |
Giardiasis is transmitted via the [[fecal-oral route|faecal-oral route]] with the ingestion of [[Microbial cyst|cyst]]s.<ref name="Barry2013">{{cite journal | vauthors = Barry MA, Weatherhead JE, Hotez PJ, Woc-Colburn L | title = Childhood parasitic infections endemic to the United States | journal = Pediatric Clinics of North America | volume = 60 | issue = 2 | pages = 471–85 | date = April 2013 | pmid = 23481112 | doi = 10.1016/j.pcl.2012.12.011 }}</ref> Primary routes are personal contact and contaminated water and food.<ref name="Barry2013"/> The cysts can stay infectious for up to three months in cold water.<ref name=Auer2012/> |
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Many people with ''Giardia'' infections have no or few symptoms.<ref name=Gard2001>{{cite journal | vauthors = Gardner TB, Hill DR | title = Treatment of giardiasis | journal = Clinical Microbiology Reviews | volume = 14 | issue = 1 | pages = 114–28 | date = January 2001 | pmid = 11148005 | pmc = 88965 | doi = 10.1128/CMR.14.1.114-128.2001 }}</ref> They may, however, still spread the disease.<ref name=Gard2001/> |
Many people with ''Giardia'' infections have no or few symptoms.<ref name=Gard2001>{{cite journal | vauthors = Gardner TB, Hill DR | title = Treatment of giardiasis | journal = Clinical Microbiology Reviews | volume = 14 | issue = 1 | pages = 114–28 | date = January 2001 | pmid = 11148005 | pmc = 88965 | doi = 10.1128/CMR.14.1.114-128.2001 }}</ref> They may, however, still spread the disease.<ref name=Gard2001/> |
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==Pathophysiology== |
==Pathophysiology== |
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[[File:Giardia LifeCycle.gif|thumb|upright=1.4|Life cycle of ''Giardia'']] |
[[File:Giardia LifeCycle.gif|thumb|upright=1.4|Life cycle of ''Giardia'']] |
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The life cycle of ''Giardia'' consists of a cyst form and a trophozoite form.<ref name=":4" /> The cyst form is infectious and once it has found a host, transforms into the trophozoite form.<ref name=":4" /> This trophozoite attaches to the intestinal wall and replicates within the gut.<ref name=":4" /> As trophozoites continue along the gastrointestinal tract, they convert back to their cyst form which is then excreted with |
The life cycle of ''Giardia'' consists of a cyst form and a trophozoite form.<ref name=":4" /> The cyst form is infectious and once it has found a host, transforms into the trophozoite form.<ref name=":4" /> This trophozoite attaches to the intestinal wall and replicates within the gut.<ref name=":4" /> As trophozoites continue along the gastrointestinal tract, they convert back to their cyst form which is then excreted with faeces.<ref name="BMJ2016" /> Ingestion of only a few of these cysts is needed to generate infection in another host.<ref name=":6" /> |
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Infection with ''Giardia'' results in decreased expression of [[brush border]] enzymes, morphological changes to the [[microvillus]], increased intestinal permeability, and [[apoptosis|programmed cell death]] of small intestinal [[Epithelium|epithelial]] cells.<ref name=":5">{{cite journal | vauthors = Buret AG | title = Pathophysiology of enteric infections with Giardia duodenalius | journal = Parasite | volume = 15 | issue = 3 | pages = 261–5 | date = September 2008 | pmid = 18814692 | doi = 10.1051/parasite/2008153261 | doi-access = free }}</ref> Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it.<ref>{{cite journal | vauthors = Bartelt LA, Sartor RB | title = Advances in understanding Giardia: determinants and mechanisms of chronic sequelae | journal = F1000Prime Reports | volume = 7 | issue = 62 | pages = 62 | date = 2015-05-26 | pmid = 26097735 | pmc = 4447054 | doi = 10.12703/P7-62 }}</ref> |
Infection with ''Giardia'' results in decreased expression of [[brush border]] enzymes, morphological changes to the [[microvillus]], increased intestinal permeability, and [[apoptosis|programmed cell death]] of small intestinal [[Epithelium|epithelial]] cells.<ref name=":5">{{cite journal | vauthors = Buret AG | title = Pathophysiology of enteric infections with Giardia duodenalius | journal = Parasite | volume = 15 | issue = 3 | pages = 261–5 | date = September 2008 | pmid = 18814692 | doi = 10.1051/parasite/2008153261 | doi-access = free }}</ref> Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it.<ref>{{cite journal | vauthors = Bartelt LA, Sartor RB | title = Advances in understanding Giardia: determinants and mechanisms of chronic sequelae | journal = F1000Prime Reports | volume = 7 | issue = 62 | pages = 62 | date = 2015-05-26 | pmid = 26097735 | pmc = 4447054 | doi = 10.12703/P7-62 | doi-access = free }}</ref> |
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The attachment of [[trophozoites]] causes villous flattening and inhibition of [[disaccharidase|enzymes that break down disaccharide sugars]] in the intestines.<ref name=Cot2011 /><ref name=":5" /> Ultimately, the [[Microbiome|community of microorganisms]] that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in |
The attachment of [[trophozoites]] causes villous flattening and inhibition of [[disaccharidase|enzymes that break down disaccharide sugars]] in the intestines.<ref name=Cot2011 /><ref name=":5" /> Ultimately, the [[Microbiome|community of microorganisms]] that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhoea, one of the predominant symptoms.<ref name=":5" /> In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases is highly varied.{{citation needed|date=May 2021}} |
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The species ''Giardia intestinalis'' uses [[Protease|enzymes that break down proteins]] to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host [[T cell|T lymphocytes]] attack endothelial cells that have been injured in order to remove the cell.<ref name=Cot2011 /> This occurs after the disruption of proteins that [[Tight junction|connect brush border endothelial cells to one another]].<ref name=":5" /> The result is increased intestinal permeability.<ref name=":5" /> |
The species ''Giardia intestinalis'' uses [[Protease|enzymes that break down proteins]] to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host [[T cell|T lymphocytes]] attack endothelial cells that have been injured in order to remove the cell.<ref name=Cot2011 /> This occurs after the disruption of proteins that [[Tight junction|connect brush border endothelial cells to one another]].<ref name=":5" /> The result is increased intestinal permeability.<ref name=":5" /> |
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''Giardia'' protects its own growth by reducing the formation of the gas [[nitric oxide]] by consuming all local [[arginine]], which is the [[amino acid]] necessary to make nitric oxide.<ref name=Cot2011 /> Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.<ref>{{cite web|last=Muhkerjee|first=Sandeep|title=Giardiasis|url=http://emedicine.medscape.com/article/176718-overview#a0104|publisher=Medscape Reference|access-date=21 November 2012|url-status=live|archive-url=https://web.archive.org/web/20121117033849/http://emedicine.medscape.com/article/176718-overview#a0104|archive-date=17 November 2012}}</ref> |
''Giardia'' protects its own growth by reducing the formation of the gas [[nitric oxide]] by consuming all local [[arginine]], which is the [[amino acid]] necessary to make nitric oxide.<ref name=Cot2011 /> Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.<ref>{{cite web|last=Muhkerjee|first=Sandeep|title=Giardiasis|url=http://emedicine.medscape.com/article/176718-overview#a0104|publisher=Medscape Reference|access-date=21 November 2012|url-status=live|archive-url=https://web.archive.org/web/20121117033849/http://emedicine.medscape.com/article/176718-overview#a0104|archive-date=17 November 2012}}</ref> |
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== Host |
== Host defence == |
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Host |
Host defence against ''Giardia'' consists of natural barriers, production of nitric oxide, and activation of the innate and adaptive immune systems.{{citation needed|date=January 2023}} |
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=== Natural barriers === |
=== Natural barriers === |
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Natural barriers defend against parasite entering the host's body. Natural barriers consist of [[mucus]] layers, bile salt, [[protease]]s, and [[lipase]]s. Additionally, [[peristalsis]] and the renewal of [[enterocyte]]s provide further protection against parasites.<ref>{{Cite journal|last=Eckmann|first=Lars|date=May 2003|title=Mucosal defences against Giardia|url=http://dx.doi.org/10.1046/j.1365-3024.2003.00634.x|journal=Parasite Immunology|volume=25|issue=5|pages=259–270|doi=10.1046/j.1365-3024.2003.00634.x|pmid=12969444|s2cid=7155680|issn=0141-9838}}</ref><ref>{{Cite journal|last=Thompson|first=R. C. Andrew|date=July 2011|title=Giardia infections|url=http://dx.doi.org/10.1093/med/9780198570028.003.0052|journal=Oxford Medicine Online|doi=10.1093/med/9780198570028.003.0052|isbn=978-0-19-969782-3}}</ref> |
Natural barriers defend against the parasite entering the host's body. Natural barriers consist of [[mucus]] layers, bile salt, [[protease]]s, and [[lipase]]s. Additionally, [[peristalsis]] and the renewal of [[enterocyte]]s provide further protection against parasites.<ref>{{Cite journal|last=Eckmann|first=Lars|date=May 2003|title=Mucosal defences against Giardia|url=http://dx.doi.org/10.1046/j.1365-3024.2003.00634.x|journal=Parasite Immunology|volume=25|issue=5|pages=259–270|doi=10.1046/j.1365-3024.2003.00634.x|pmid=12969444|s2cid=7155680|issn=0141-9838}}</ref><ref>{{Cite journal|last=Thompson|first=R. C. Andrew|date=July 2011|title=Giardia infections|url=http://dx.doi.org/10.1093/med/9780198570028.003.0052|journal=Oxford Medicine Online|doi=10.1093/med/9780198570028.003.0052|isbn=978-0-19-969782-3}}</ref> |
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=== Nitric oxide production === |
=== Nitric oxide production === |
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Antibodies inhibit parasite replication and also induce parasite death via the classical pathway of complement.{{citation needed|date=June 2022}} |
Antibodies inhibit parasite replication and also induce parasite death via the classical pathway of complement.{{citation needed|date=June 2022}} |
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Infection with ''Giardia'' typically results in a strong antibody response against the parasite. While IgG is made in significant amounts, IgA is believed to be more important in parasite control. IgA is the most abundant isotype in intestinal secretions, and it is also the dominant isotype in mother's milk. Antibodies in mother's milk protect children against giardiasis (passive |
Infection with ''Giardia'' typically results in a strong antibody response against the parasite. While IgG is made in significant amounts, IgA is believed to be more important in parasite control. IgA is the most abundant isotype in intestinal secretions, and it is also the dominant isotype in a mother's milk. Antibodies in a mother's milk protect children against giardiasis (passive immunisation).<ref>{{Cite journal|last1=Tellez|first1=Aleyda|last2=Winiecka-krusnell|first2=Jadwiga|last3=Paniagua|first3=Margarita|last4=Linder|first4=Ewert|date=May 2003|title=Antibodies in Mother's Milk Protect Children Against Giardiasis|url=http://dx.doi.org/10.1080/00365540310008041|journal=Scandinavian Journal of Infectious Diseases|volume=35|issue=5|pages=322–325|doi=10.1080/00365540310008041|pmid=12875519|s2cid=12621232|issn=0036-5548}}</ref> |
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==== T |
==== T-cells ==== |
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The major aspect of adaptive immune responses is the [[T |
The major aspect of adaptive immune responses is the [[T-cell]] response. ''Giardia'' is an extracellular pathogen. Therefore CD4+ helper T-cells are primarily responsible for this protective effect.<ref name=":10">{{Cite journal|last1=Singer|first1=Steven M.|last2=Nash|first2=Theodore E.|date=2000-01-01|title=T-Cell-Dependent Control of Acute Giardia lamblia Infections in Mice|journal=Infection and Immunity|volume=68|issue=1|pages=170–175|doi=10.1128/iai.68.1.170-175.2000|pmid=10603384|pmc=97117|issn=1098-5522|doi-access=free}}</ref> |
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One role of helper T |
One role of helper T-cells is to promote antibody production and isotype switching. Other roles include cytokine production (Il-4,IL-9) to help recruit other effector cells of the immune response.<ref name=":10" /><ref>{{Cite journal|last1=Scott|first1=Kevin G.-E.|last2=Yu|first2=Linda C. H.|last3=Buret|first3=André G.|date=June 2004|title=Role of CD8+ and CD4+ T Lymphocytes in Jejunal Mucosal Injury during Murine Giardiasis|journal=Infection and Immunity|volume=72|issue=6|pages=3536–3542|doi=10.1128/iai.72.6.3536-3542.2004|pmid=15155662|pmc=415705|issn=0019-9567|doi-access=free}}</ref> |
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==Diagnosis== |
==Diagnosis== |
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[[File:Histopathology of Giardia lamblia in duodenum.png|thumb|A duodenal biopsy may incidentally detect Giardia organisms, as in this [[H&E stain]]ed sample.<ref>{{cite journal |author1=Kalas MA |author2=Alduaij A |author3=Alkhatib AA| title=Incidental Diagnosis of Duodenal Giardiasis. | journal=Cureus | year= 2021 | volume= 13 | issue= 6 | pages= e15499 | pmid=34268030 | doi=10.7759/cureus.15499 | pmc=8262110 }}<br>- "This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0."</ref>]] |
[[File:Histopathology of Giardia lamblia in duodenum.png|thumb|A duodenal biopsy may incidentally detect ''Giardia'' organisms, as in this [[H&E stain]]ed sample.<ref>{{cite journal |author1=Kalas MA |author2=Alduaij A |author3=Alkhatib AA| title=Incidental Diagnosis of Duodenal Giardiasis. | journal=Cureus | year= 2021 | volume= 13 | issue= 6 | pages= e15499 | pmid=34268030 | doi=10.7759/cureus.15499 |doi-access=free | pmc=8262110 }}<br>- "This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0."</ref>]] |
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* According to the CDC, detection of antigens on the surface of organisms in stool specimens is the current test of choice for diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques.<ref>{{cite web |url=https://www.cdc.gov/dpdx/diagnosticProcedures/stool/antigendetection.html |title=Stool Specimens - Detection of Parasite Antigens |website=CDC |access-date=2017-09-09 |url-status=live |archive-url=https://web.archive.org/web/20170617214619/https://www.cdc.gov/dpdx/diagnosticprocedures/stool/antigendetection.html |archive-date=2017-06-17 }}</ref> |
* According to the CDC, detection of antigens on the surface of organisms in stool specimens is the current test of choice for diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques.<ref>{{cite web |url=https://www.cdc.gov/dpdx/diagnosticProcedures/stool/antigendetection.html |title=Stool Specimens - Detection of Parasite Antigens |website=CDC |access-date=2017-09-09 |url-status=live |archive-url=https://web.archive.org/web/20170617214619/https://www.cdc.gov/dpdx/diagnosticprocedures/stool/antigendetection.html |archive-date=2017-06-17 }}</ref> |
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* A trichrome stain of preserved stool is another method used to detect ''Giardia''.<ref>{{cite web |url=http://ltd.aruplab.com/Tests/Pub/2002272 |title=Ova and Parasite Exam, Fecal (Immunocompromised or Travel History) |access-date=2014-10-29 |url-status=live |archive-url=https://web.archive.org/web/20141029104806/http://ltd.aruplab.com/Tests/Pub/2002272 |archive-date=2014-10-29 }}</ref> |
* A trichrome stain of preserved stool is another method used to detect ''Giardia''.<ref>{{cite web |url=http://ltd.aruplab.com/Tests/Pub/2002272 |title=Ova and Parasite Exam, Fecal (Immunocompromised or Travel History) |access-date=2014-10-29 |url-status=live |archive-url=https://web.archive.org/web/20141029104806/http://ltd.aruplab.com/Tests/Pub/2002272 |archive-date=2014-10-29 }}</ref> |
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Although the evidence linking the drinking of water in the North American wilderness and giardiasis has been questioned, a number of studies raise concern.<ref>{{cite journal|author1=Julia E. Painter, PhD |author2=Julia W. Gargano, PhD |author3=Sarah A. Collier, MPH |author4=Jonathan S. Yoder, MPH|title=Giardiasis Surveillance—United States, 2011–2012|journal= MMWR Supplements|date=2015|volume=64|issue=Suppl 3|pages=15–25|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/ss6403a2.htm|access-date=31 March 2018 |pmid=25928582}}</ref> Most if not all CDC verified backcountry giardiasis outbreaks have been attributed to water. Surveillance data (for 2013 and 2014) reports six outbreaks (96 cases) of waterborne giardiasis contracted from rivers, streams or springs<ref>{{cite journal | vauthors = McClung RP, Roth DM, Vigar M, Roberts VA, Kahler AM, Cooley LA, Hilborn ED, Wade TJ, Fullerton KE, Yoder JS, Hill VR | display-authors = 6 | title = Waterborne Disease Outbreaks Associated With Environmental and Undetermined Exposures to Water - United States, 2013-2014 | language = en-us | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 66 | issue = 44 | pages = 1222–1225 | date = November 2017 | pmid = 29120997 | pmc = 5679586 | doi = 10.15585/mmwr.mm6644a4 }}</ref> and less than 1% of reported giardiasis cases are associated with outbreaks.<ref>{{cite journal|title=Giardiasis Surveillance — United States, 2009–2010|website=www.cdc.gov|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/ss6105a2.htm|language=en}}</ref> |
Although the evidence linking the drinking of water in the North American wilderness and giardiasis has been questioned, a number of studies raise concern.<ref>{{cite journal|author1=Julia E. Painter, PhD |author2=Julia W. Gargano, PhD |author3=Sarah A. Collier, MPH |author4=Jonathan S. Yoder, MPH|title=Giardiasis Surveillance—United States, 2011–2012|journal= MMWR Supplements|date=2015|volume=64|issue=Suppl 3|pages=15–25|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/ss6403a2.htm|access-date=31 March 2018 |pmid=25928582}}</ref> Most if not all CDC verified backcountry giardiasis outbreaks have been attributed to water. Surveillance data (for 2013 and 2014) reports six outbreaks (96 cases) of waterborne giardiasis contracted from rivers, streams or springs<ref>{{cite journal | vauthors = McClung RP, Roth DM, Vigar M, Roberts VA, Kahler AM, Cooley LA, Hilborn ED, Wade TJ, Fullerton KE, Yoder JS, Hill VR | display-authors = 6 | title = Waterborne Disease Outbreaks Associated With Environmental and Undetermined Exposures to Water - United States, 2013-2014 | language = en-us | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 66 | issue = 44 | pages = 1222–1225 | date = November 2017 | pmid = 29120997 | pmc = 5679586 | doi = 10.15585/mmwr.mm6644a4 }}</ref> and less than 1% of reported giardiasis cases are associated with outbreaks.<ref>{{cite journal|title=Giardiasis Surveillance — United States, 2009–2010|website=www.cdc.gov|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/ss6105a2.htm|language=en}}</ref> |
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Person-to-person transmission accounts for the majority of ''Giardia'' infections, and is usually associated with poor hygiene and sanitation. ''Giardia'' is often found on the surface of the ground, in the soil, in undercooked foods, and in water, and on hands that have not been properly cleaned after handling infected [[feces]].<ref>{{cite web |title=Giardia |date=March 2011 |work=Parasites |publisher=[[Centers for Disease Control and Prevention]] |url=https://www.cdc.gov/parasites/giardia/}}</ref> Water-borne [[Transmission (medicine)|transmission]] is associated with the ingestion of contaminated water. In the U.S., outbreaks typically occur in small water systems using inadequately treated surface water. [[Sexually transmitted disease|Venereal]] transmission happens through |
Person-to-person transmission accounts for the majority of ''Giardia'' infections, and is usually associated with poor hygiene and sanitation. ''Giardia'' is often found on the surface of the ground, in the soil, in undercooked foods, and in water, and on hands that have not been properly cleaned after handling infected [[feces|faeces]].<ref>{{cite web |title=Giardia |date=March 2011 |work=Parasites |publisher=[[Centers for Disease Control and Prevention]] |url=https://www.cdc.gov/parasites/giardia/}}</ref> Water-borne [[Transmission (medicine)|transmission]] is associated with the ingestion of contaminated water. In the U.S., outbreaks typically occur in small water systems using inadequately treated surface water. [[Sexually transmitted disease|Venereal]] transmission happens through faecal-oral contamination. Additionally, nappy/diaper changing and inadequate handwashing are risk factors for transmission from infected children. Lastly, food-borne epidemics of ''Giardia'' have developed through the contamination of food by infected food-handlers.<ref name="pennardt_g">{{EMedicine|article|176718|Giardiasis}}</ref> |
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=== Vaccine === |
=== Vaccine === |
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There are no vaccines for humans yet, however there are several vaccine candidates in development. They are targeting: recombinant proteins, DNA vaccine, variant-specific surface proteins (VSP), cyst wall proteins (CWP), giadins and enzymes.<ref>{{Cite journal|last1=Davids|first1=Barbara J.|last2=Liu|first2=Ching M.|last3=Hanson|first3=Elaine M.|last4=Le|first4=Christine H. Y.|last5=Ang|first5=Jonathan|last6=Hanevik|first6=Kurt|last7=Fischer|first7=Marvin|last8=Radunovic|first8=Matej|last9=Langeland|first9=Nina|last10=Ferella|first10=Marcela|last11=Svärd|first11=Staffan G.|date=2019-04-08|title=Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia|journal=Infection and Immunity|volume=87|issue=6|doi=10.1128/iai.00219-19|pmid=30962402|pmc=6529650|issn=0019-9567|doi-access=free}}</ref> Researchers at [[National Scientific and Technical Research Council|CONICET]] have produced an oral vaccine after engineering |
There are no vaccines for humans yet, however there are several vaccine candidates in development. They are targeting: recombinant proteins, DNA vaccine, variant-specific surface proteins (VSP), cyst wall proteins (CWP), giadins and enzymes.<ref>{{Cite journal|last1=Davids|first1=Barbara J.|last2=Liu|first2=Ching M.|last3=Hanson|first3=Elaine M.|last4=Le|first4=Christine H. Y.|last5=Ang|first5=Jonathan|last6=Hanevik|first6=Kurt|last7=Fischer|first7=Marvin|last8=Radunovic|first8=Matej|last9=Langeland|first9=Nina|last10=Ferella|first10=Marcela|last11=Svärd|first11=Staffan G.|date=2019-04-08|title=Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia|journal=Infection and Immunity|volume=87|issue=6|doi=10.1128/iai.00219-19|pmid=30962402|pmc=6529650|issn=0019-9567|doi-access=free}}</ref> Researchers at [[National Scientific and Technical Research Council|CONICET]] have produced an oral vaccine after engineering customised proteins mimicking those expressed on the surface of Giardia trophozoites. The vaccine has proven effective in mice.<ref>{{Cite journal |last1=Serradell |first1=Marianela C. |last2=Rupil |first2=Lucía L. |last3=Martino |first3=Román A. |last4=Prucca |first4=César G. |last5=Carranza |first5=Pedro G. |last6=Saura |first6=Alicia |last7=Fernández |first7=Elmer A. |last8=Gargantini |first8=Pablo R. |last9=Tenaglia |first9=Albano H. |last10=Petiti |first10=Juan P. |last11=Tonelli |first11=Renata R. |last12=Reinoso-Vizcaino |first12=Nicolás |last13=Echenique |first13=José |last14=Berod |first14=Luciana |last15=Piaggio |first15=Eliane |date=2019-01-21 |title=Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins |journal=Nature Communications |language=en |volume=10 |issue=1 |pages=361 |doi=10.1038/s41467-018-08265-9 |pmid=30664644 |issn=2041-1723|pmc=6341118 |bibcode=2019NatCo..10..361S }}</ref><ref>{{Cite journal |last1=Rupil |first1=Lucía Lara |last2=Serradell |first2=Marianela Del Carmen |last3=Luján |first3=Hugo Daniel |date=January 2020 |title=Using Protozoan Surface Proteins for Effective Oral Vaccination |url=https://pubmed.ncbi.nlm.nih.gov/31362858/ |journal=Trends in Parasitology |volume=36 |issue=1 |pages=7–10 |doi=10.1016/j.pt.2019.07.004 |issn=1471-5007 |pmid=31362858|s2cid=198999660 }}</ref> |
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At present, one commercially available vaccine exists – GiardiaVax, made from ''G. lamblia'' whole trophozoite lysate. It is a vaccine for veterinary use only in dogs and cats. GiardiaVax should promote production of specific antibodies.<ref>{{cite journal |last1=Palatnik-de-Sousa |first1=CB |last2=Nico |first2=D |title=The Delay in the Licensing of Protozoal Vaccines: A Comparative History. |journal=Frontiers in Immunology |date=2020 |volume=11 |pages=204 |doi=10.3389/fimmu.2020.00204 |pmid=32210953 |pmc=7068796 |doi-access=free}}</ref> |
At present, one commercially available vaccine exists – GiardiaVax, made from ''G. lamblia'' whole trophozoite lysate. It is a vaccine for veterinary use only in dogs and cats. GiardiaVax should promote production of specific antibodies.<ref>{{cite journal |last1=Palatnik-de-Sousa |first1=CB |last2=Nico |first2=D |title=The Delay in the Licensing of Protozoal Vaccines: A Comparative History. |journal=Frontiers in Immunology |date=2020 |volume=11 |pages=204 |doi=10.3389/fimmu.2020.00204 |pmid=32210953 |pmc=7068796 |doi-access=free}}</ref> |
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Treatment is not always necessary as the infection usually resolves on its own.<ref name=Cot2011 /> However, if the illness is acute or symptoms persist and medications are needed to treat it, a [[nitroimidazole]] medication is used such as [[metronidazole]], [[tinidazole]], [[secnidazole]] or [[ornidazole]].<ref name="Barry2013"/> |
Treatment is not always necessary as the infection usually resolves on its own.<ref name=Cot2011 /> However, if the illness is acute or symptoms persist and medications are needed to treat it, a [[nitroimidazole]] medication is used such as [[metronidazole]], [[tinidazole]], [[secnidazole]] or [[ornidazole]].<ref name="Barry2013"/> |
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The [[World Health Organization]] and [[Infectious Diseases Society of America|Infectious Disease Society of America]] recommend metronidazole as first line therapy.<ref>{{cite journal | vauthors = Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, Hennessy T, Griffin PM, DuPont H, Sack RB, Tarr P, Neill M, Nachamkin I, Reller LB, Osterholm MT, Bennish ML, Pickering LK | display-authors = 6 | title = Practice guidelines for the management of infectious diarrhea | journal = Clinical Infectious Diseases | volume = 32 | issue = 3 | pages = 331–51 | date = February 2001 | pmid = 11170940 | doi = 10.1086/318514 | url = http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Diarrhea.pdf | url-status = live | archive-url = https://web.archive.org/web/20160210051836/http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Diarrhea.pdf | archive-date = February 10, 2016 | doi-access = free }}</ref><ref>{{Cite web|title = Chapter 7.5.4 Continuing Diarrhoea {{!}} ICHRC|url = http://www.ichrc.org/chapter-754-continuing-diarrhoea|website = www.ichrc.org|access-date = 2016-01-09|url-status = live|archive-url = https://web.archive.org/web/20160129235636/http://www.ichrc.org/chapter-754-continuing-diarrhoea|archive-date = 2016-01-29}}</ref> The [[US CDC]] lists metronidazole, tinidazole, and [[nitazoxanide]] as effective first-line therapies;<ref>{{cite web|title=Giardia: Treatment|url=https://www.cdc.gov/parasites/giardia/treatment.html|publisher=United States Centers for Disease Control and Prevention|access-date=10 January 2016|date=21 July 2015|quote=Several drugs can be used to treat Giardia infection. Effective treatments include metronidazole, tinidazole, and nitazoxanide<sup>1</sup>. Alternatives to these medications include paromomycin, quinacrine, and furazolidone<sup>1,2</sup>.|url-status=live|archive-url=https://web.archive.org/web/20151224232327/http://www.cdc.gov/parasites/giardia/treatment.html|archive-date=24 December 2015}}</ref> of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US [[Food and Drug Administration|FDA]].<ref name="FDA Nitazoxanide">{{cite web|title=Nitazoxanide Prescribing Information|url=http://www.alinia.com/images/Alinia-Prescribing-Information.pdf|publisher=Romark Pharmaceuticals|access-date=3 January 2016|pages=1–5|date=August 2013|url-status=dead|archive-url=https://web.archive.org/web/20160116192246/http://alinia.com/images/Alinia-Prescribing-Information.pdf|archive-date=16 January 2016}}</ref><ref>{{cite web|title=Metronidazole Prescribing Information|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/012623s066lbl.pdf|website=United States Food and Drug Administration|publisher=Pfizer|access-date=10 January 2016|pages=6–7|date=June 2015|url-status=live|archive-url=https://web.archive.org/web/20160304085137/http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/012623s066lbl.pdf|archive-date=4 March 2016}}</ref><ref>{{cite web|title=Tinidazole Prescribing Informatiuon|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021618s003lbl.pdf|website=United States Food and Drug Administration|publisher=Mission Pharma|access-date=10 January 2016|page=1|date=May 2007|url-status=live|archive-url=https://web.archive.org/web/20160304061029/http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021618s003lbl.pdf|archive-date=4 March 2016}}</ref> A meta-analysis published by the [[Cochrane (organisation)|Cochrane Collaboration]] in 2012 found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues.<ref name=":0">{{cite journal | vauthors = Granados CE, Reveiz L, Uribe LG, Criollo CP | title = Drugs for treating giardiasis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD007787 | date = December 2012 | issue = 12 | pmid = 23235648 | pmc = 6532677 | doi = 10.1002/14651858.cd007787.pub2 }}</ref> Other meta-analyses have reached similar conclusions.<ref name="Solaymani 2010">{{cite journal | vauthors = Solaymani-Mohammadi S, Genkinger JM, Loffredo CA, Singer SM | title = A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis | journal = PLOS Neglected Tropical Diseases | volume = 4 | issue = 5 | pages = e682 | date = May 2010 | pmid = 20485492 | pmc = 2867942 | doi = 10.1371/journal.pntd.0000682 | editor1-last = Keiser | editor1-first = Jennifer }}</ref> Both medications need a five to |
The [[World Health Organization|World Health Organisation]] and [[Infectious Diseases Society of America|Infectious Disease Society of America]] recommend metronidazole as first line therapy.<ref>{{cite journal | vauthors = Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, Hennessy T, Griffin PM, DuPont H, Sack RB, Tarr P, Neill M, Nachamkin I, Reller LB, Osterholm MT, Bennish ML, Pickering LK | display-authors = 6 | title = Practice guidelines for the management of infectious diarrhea | journal = Clinical Infectious Diseases | volume = 32 | issue = 3 | pages = 331–51 | date = February 2001 | pmid = 11170940 | doi = 10.1086/318514 | url = http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Diarrhea.pdf | url-status = live | archive-url = https://web.archive.org/web/20160210051836/http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Diarrhea.pdf | archive-date = February 10, 2016 | doi-access = free }}</ref><ref>{{Cite web|title = Chapter 7.5.4 Continuing Diarrhoea {{!}} ICHRC|url = http://www.ichrc.org/chapter-754-continuing-diarrhoea|website = www.ichrc.org|access-date = 2016-01-09|url-status = live|archive-url = https://web.archive.org/web/20160129235636/http://www.ichrc.org/chapter-754-continuing-diarrhoea|archive-date = 2016-01-29}}</ref> The [[US CDC]] lists metronidazole, tinidazole, and [[nitazoxanide]] as effective first-line therapies;<ref>{{cite web|title=Giardia: Treatment|url=https://www.cdc.gov/parasites/giardia/treatment.html|publisher=United States Centers for Disease Control and Prevention|access-date=10 January 2016|date=21 July 2015|quote=Several drugs can be used to treat Giardia infection. Effective treatments include metronidazole, tinidazole, and nitazoxanide<sup>1</sup>. Alternatives to these medications include paromomycin, quinacrine, and furazolidone<sup>1,2</sup>.|url-status=live|archive-url=https://web.archive.org/web/20151224232327/http://www.cdc.gov/parasites/giardia/treatment.html|archive-date=24 December 2015}}</ref> of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US [[Food and Drug Administration|FDA]].<ref name="FDA Nitazoxanide">{{cite web|title=Nitazoxanide Prescribing Information|url=http://www.alinia.com/images/Alinia-Prescribing-Information.pdf|publisher=Romark Pharmaceuticals|access-date=3 January 2016|pages=1–5|date=August 2013|url-status=dead|archive-url=https://web.archive.org/web/20160116192246/http://alinia.com/images/Alinia-Prescribing-Information.pdf|archive-date=16 January 2016}}</ref><ref>{{cite web|title=Metronidazole Prescribing Information|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/012623s066lbl.pdf|website=United States Food and Drug Administration|publisher=Pfizer|access-date=10 January 2016|pages=6–7|date=June 2015|url-status=live|archive-url=https://web.archive.org/web/20160304085137/http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/012623s066lbl.pdf|archive-date=4 March 2016}}</ref><ref>{{cite web|title=Tinidazole Prescribing Informatiuon|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021618s003lbl.pdf|website=United States Food and Drug Administration|publisher=Mission Pharma|access-date=10 January 2016|page=1|date=May 2007|url-status=live|archive-url=https://web.archive.org/web/20160304061029/http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021618s003lbl.pdf|archive-date=4 March 2016}}</ref> A meta-analysis published by the [[Cochrane (organisation)|Cochrane Collaboration]] in 2012 found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues.<ref name=":0">{{cite journal | vauthors = Granados CE, Reveiz L, Uribe LG, Criollo CP | title = Drugs for treating giardiasis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD007787 | date = December 2012 | issue = 12 | pmid = 23235648 | pmc = 6532677 | doi = 10.1002/14651858.cd007787.pub2 }}</ref> Other meta-analyses have reached similar conclusions.<ref name="Solaymani 2010">{{cite journal | vauthors = Solaymani-Mohammadi S, Genkinger JM, Loffredo CA, Singer SM | title = A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis | journal = PLOS Neglected Tropical Diseases | volume = 4 | issue = 5 | pages = e682 | date = May 2010 | pmid = 20485492 | pmc = 2867942 | doi = 10.1371/journal.pntd.0000682 | editor1-last = Keiser | editor1-first = Jennifer | doi-access = free }}</ref> Both medications need a five to ten day-long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole or nitazoxanide was felt to be of very low quality.<ref name=":0" /> While tinidazole has side effects and efficacy similar to those of metronidazole, it is administered with a single dose.<ref name="Gard2001" /> |
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Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories.<ref name=":6" /><ref name=":1">{{cite journal | vauthors = Leitsch D | title = Giardia lamblia | journal = Current Tropical Medicine Reports | volume = 2 | issue = 3 | pages = 128–135 | date = 2015-07-07 | pmid = 26258002 | pmc = 4523694 | doi = 10.1007/s40475-015-0051-1 }}</ref> The exact mechanism of resistance to all of these medications is not well understood.<ref name=":1" /> In the case of nitroimidazole-resistant strains of ''Giardia'', other drugs are available which have showed efficacy in treatment including [[quinacrine]], nitazoxanide, [[bacitracin zinc]], [[furazolidone]] and [[paromomycin]].<ref name="Gard2001"/> [[Mepacrine]] may also be used for refractory cases.<ref name=":6" /> |
Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories.<ref name=":6" /><ref name=":1">{{cite journal | vauthors = Leitsch D | title = Giardia lamblia | journal = Current Tropical Medicine Reports | volume = 2 | issue = 3 | pages = 128–135 | date = 2015-07-07 | pmid = 26258002 | pmc = 4523694 | doi = 10.1007/s40475-015-0051-1 }}</ref> The exact mechanism of resistance to all of these medications is not well understood.<ref name=":1" /> In the case of nitroimidazole-resistant strains of ''Giardia'', other drugs are available which have showed efficacy in treatment including [[quinacrine]], nitazoxanide, [[bacitracin zinc]], [[furazolidone]] and [[paromomycin]].<ref name="Gard2001"/> [[Mepacrine]] may also be used for refractory cases.<ref name=":6" /> |
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Probiotics, when given in combination with the standard treatment, |
Probiotics, when given in combination with the standard treatment, have been shown to assist with clearance of ''Giardia''.<ref>{{Cite journal|last1=Lalle|first1=Marco|last2=Hanevik|first2=Kurt|date=2018-10-24|title=Treatment-refractory giardiasis: challenges and solutions|journal=Infection and Drug Resistance|volume=11|pages=1921–1933|doi=10.2147/IDR.S141468|issn=1178-6973|pmc=6207226|pmid=30498364 |doi-access=free }}</ref> |
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During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, resulting in less exposure to the |
During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, resulting in less exposure to the foetus.<ref>{{cite journal | vauthors = Farthing MJ | s2cid = 19657328 | title = Treatment options for the eradication of intestinal protozoa | journal = Nature Clinical Practice. Gastroenterology & Hepatology | volume = 3 | issue = 8 | pages = 436–45 | date = August 2006 | pmid = 16883348 | doi = 10.1038/ncpgasthep0557 }}</ref> Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for [[trichomonas]] in pregnancy.<ref name="Gard2001"/><ref>{{cite journal | vauthors = Workowski KA, Bolan GA | title = Sexually transmitted diseases treatment guidelines, 2015 | journal = MMWR. Recommendations and Reports | volume = 64 | issue = RR-03 | pages = 1–137 | date = June 2015 | pmid = 26042815 | pmc = 5885289 }}</ref> |
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==Prognosis== |
==Prognosis== |
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In people with a properly functioning immune system, infection may resolve without medication.<ref name=Cot2011 /> A small portion, however, develop a chronic infection.<ref name=Cot2011 /> People with an impaired immune system are at higher risk of chronic infection.<ref name=Cot2011 /> Medication is an effective cure for nearly all people although there is growing drug-resistance.<ref name="BMJ2016" /><ref name=":3">{{Cite book|title=Harrison's principles of internal medicine.|others=Kasper, Dennis L.,, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Longo, Dan L. (Dan Louis), 1949-, Jameson, J. Larry,, Loscalzo, Joseph|isbn=9780071802154|edition=19th|location=New York|oclc=893557976|last1 = Kasper|first1 = Dennis L.|last2 = Larry Jameson|first2 = J.|last3 = Hauser|first3 = Stephen L.|last4 = Loscalzo|first4 = Joseph|last5 = Fauci|first5 = Anthony S.|last6 = Longo|first6 = Dan L.|date = 2015-04-08}}</ref><ref name=":6">{{cite journal | vauthors = Carter ER, Nabarro LE, Hedley L, Chiodini PL | title = Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions | journal = Clinical Microbiology and Infection | volume = 24 | issue = 1 | pages = 37–42 | date = January 2018 | pmid = 28624613 | doi = 10.1016/j.cmi.2017.05.028 | doi-access = free }}</ref> |
In people with a properly functioning immune system, infection may resolve without medication.<ref name=Cot2011 /> A small portion, however, develop a chronic infection.<ref name=Cot2011 /> People with an impaired immune system are at higher risk of chronic infection.<ref name=Cot2011 /> Medication is an effective cure for nearly all people although there is growing drug-resistance.<ref name="BMJ2016" /><ref name=":3">{{Cite book|title=Harrison's principles of internal medicine.|others=Kasper, Dennis L.,, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Longo, Dan L. (Dan Louis), 1949-, Jameson, J. Larry,, Loscalzo, Joseph|isbn=9780071802154|edition=19th|location=New York|oclc=893557976|last1 = Kasper|first1 = Dennis L.|last2 = Larry Jameson|first2 = J.|last3 = Hauser|first3 = Stephen L.|last4 = Loscalzo|first4 = Joseph|last5 = Fauci|first5 = Anthony S.|last6 = Longo|first6 = Dan L.|date = 2015-04-08}}</ref><ref name=":6">{{cite journal | vauthors = Carter ER, Nabarro LE, Hedley L, Chiodini PL | title = Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions | journal = Clinical Microbiology and Infection | volume = 24 | issue = 1 | pages = 37–42 | date = January 2018 | pmid = 28624613 | doi = 10.1016/j.cmi.2017.05.028 | doi-access = free }}</ref> |
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Children with chronic giardiasis are at risk for failure to thrive as well as more long-lasting sequelae such as growth stunting.<ref>{{cite journal | vauthors = Donowitz JR, Alam M, Kabir M, Ma JZ, Nazib F, Platts-Mills JA, Bartelt LA, Haque R, Petri WA | display-authors = 6 | title = A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea | journal = Clinical Infectious Diseases | volume = 63 | issue = 6 | pages = 792–7 | date = September 2016 | pmid = 27313261 | pmc = 4996141 | doi = 10.1093/cid/ciw391 }}</ref> Up to half of infected people develop a temporary [[lactose intolerance]] leading symptoms that may mimic a chronic infection.<ref name="BMJ2016" /> Some people experience post-infectious [[irritable bowel syndrome]] after the infection has cleared.<ref name=Cot2011 /> Giardiasis has also been implicated in the development of [[food allergies]].<ref name=Cot2011 /> This is thought to be due to its effect on intestinal permeability.<ref name=Cot2011 /> |
Children with chronic giardiasis are at risk for failure to thrive as well as more long-lasting sequelae such as growth stunting.<ref>{{cite journal | vauthors = Donowitz JR, Alam M, Kabir M, Ma JZ, Nazib F, Platts-Mills JA, Bartelt LA, Haque R, Petri WA | display-authors = 6 | title = A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea | journal = Clinical Infectious Diseases | volume = 63 | issue = 6 | pages = 792–7 | date = September 2016 | pmid = 27313261 | pmc = 4996141 | doi = 10.1093/cid/ciw391 }}</ref> Up to half of infected people develop a temporary [[lactose intolerance]] leading to symptoms that may mimic a chronic infection.<ref name="BMJ2016" /> Some people experience post-infectious [[irritable bowel syndrome]] after the infection has cleared.<ref name=Cot2011 /> Giardiasis has also been implicated in the development of [[food allergies]].<ref name=Cot2011 /> This is thought to be due to its effect on intestinal permeability.<ref name=Cot2011 /> |
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==Epidemiology== |
==Epidemiology== |
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[[File:US giardiasis incidence 2005.gif|upright=1.3|thumb|Rates of giardiasis in 2005 in the United States]] |
[[File:US giardiasis incidence 2005.gif|upright=1.3|thumb|Rates of giardiasis in 2005 in the United States]] |
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In some [[developing countries]] ''Giardia'' is present in 30% of the population.<ref name=Auer2012>{{cite book|last=Auerbach|first=Paul S.|title=Wilderness medicine|date=2012|publisher=Elsevier/Mosby|location=Philadelphia, PA|isbn=9781437716788|pages=Chapter 68|edition= 6th}}</ref> In the United States it is estimated that it is present in 3–7% of the population.<ref name=Auer2012/> |
In some [[developing countries]] ''Giardia'' is present in 30% of the population.<ref name=Auer2012>{{cite book|last=Auerbach|first=Paul S.|title=Wilderness medicine|date=2012|publisher=Elsevier/Mosby|location=Philadelphia, PA|isbn=9781437716788|pages=Chapter 68|edition= 6th}}</ref> In the United States it is estimated that it is present in 3–7% of the population.<ref name=Auer2012/> Giardiasis is associated with impaired growth and development in children, particularly influencing a country's economic growth by affecting Disability Adjusted Life Year (DALY) rates.<ref>{{Cite journal |last=Adam |first=Rodney D. |title=Biology of Giardia lamblia |journal=Clinical Microbiology Reviews |date=2001 |language=en |volume=14 |issue=3 |pages=447–475 |doi=10.1128/CMR.14.3.447-475.2001 |issn=0893-8512 |pmc=88984 |pmid=11432808}}</ref><ref>{{Cite journal |last1=Dormond |first1=Megan |last2=Gutierrez |first2=Ramiro L. |last3=Porter |first3=Chad K. |date=December 2016 |title=Giardia lamblia infection increases risk of chronic gastrointestinal disorders |journal=Tropical Diseases, Travel Medicine and Vaccines |language=en |volume=2 |issue=1 |page=17 |doi=10.1186/s40794-016-0030-0 |issn=2055-0936|doi-access=free |pmid=28883961 |pmc=5530925 }}</ref> |
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The number of reported cases in the United States in 2018 was 15,584.<ref name=":2">{{Cite web|url=https://wonder.cdc.gov/nndss/static/2018/annual/2018-table2f.html|title= |
The number of reported cases in the United States in 2018 was 15,584.<ref name=":2">{{Cite web|url=https://wonder.cdc.gov/nndss/static/2018/annual/2018-table2f.html|title=Table 2f. Annual reported cases of notifiable diseases, by region and reporting area - - United States and U.S. Territories, 2018|website=wonder.cdc.gov|access-date=2019-11-13}}</ref> All states that classify giardiasis as a notifiable disease had cases of giardiasis.<ref name=":2" /> The states of Illinois, Kentucky, Mississippi, North Carolina, Oklahoma, Tennessee, Texas, and Vermont did not notify the Center for Disease Control regarding cases in 2018.<ref name=":2" /> There are seasonal trends associated with giardiasis.<ref>{{Cite journal|last1=Painter|first1=Julia E.|last2=Gargano|first2=Julia W.|last3=Collier|first3=Sarah A.|last4=Yoder|first4=Jonathan S. |date=2015-05-01|title=Giardiasis surveillance -- United States, 2011-2012|journal=MMWR Supplements|volume=64|issue=3|pages=15–25|issn=2380-8942|pmid=25928582}}</ref> July, August, and September are the months with the highest incidence of giardiasis in the United States.<ref>{{cite journal|author1=Jonathan S. Yoder, MPH |author2=Julia W. Gargano, PhD |author3=Ryan M. Wallace, DVM |author4=Michael J. Beach, PhD|title=Giardiasis Surveillance-United States, 2009-2010|journal=Morbidity and Mortality Weekly Report. Surveillance Summaries |volume=61|issue=5|pages=13–23|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/ss6105a2.htm|publisher=Centers of Disease Control and Prevention|access-date=30 November 2017|pmid=22951494|year=2012}}</ref> |
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In the ECDC's (European Centre for Disease Prevention and Control) annual epidemiological report containing 2014 data, 17,278 confirmed giardiasis cases were reported by 23 of the 31 countries that are members of the EU/EEA.<ref name=":8" /> Germany reported the highest number at 4,011 cases.<ref name=":8" /> Following Germany, the UK reported 3,628 confirmed giardiasis cases. Together, this accounts for 44% of total reported cases.<ref name=":8">{{cite web|title=Giardiasis- Annual Epidemiological Report 2016|url=https://ecdc.europa.eu/en/publications-data/giardiasis-annual-epidemiological-report-2016-2014-data|website |
In the ECDC's (European Centre for Disease Prevention and Control) annual epidemiological report containing 2014 data, 17,278 confirmed giardiasis cases were reported by 23 of the 31 countries that are members of the EU/EEA.<ref name=":8" /> Germany reported the highest number at 4,011 cases.<ref name=":8" /> Following Germany, the UK reported 3,628 confirmed giardiasis cases. Together, this accounts for 44% of total reported cases.<ref name=":8">{{cite web|title=Giardiasis- Annual Epidemiological Report 2016|url=https://ecdc.europa.eu/en/publications-data/giardiasis-annual-epidemiological-report-2016-2014-data|website=European Centre for Disease Prevention and Control|access-date=30 November 2017|date=2017-01-30}}</ref> |
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==Research== |
==Research== |
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Some intestinal parasitic infections may play a role in [[irritable bowel syndrome]]<ref>{{cite journal | vauthors = Stark D, van Hal S, Marriott D, Ellis J, Harkness J | title = Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis | journal = International Journal for Parasitology | volume = 37 | issue = 1 | pages = 11–20 | date = January 2007 | pmid = 17070814 | doi = 10.1016/j.ijpara.2006.09.009 }}</ref> and other long-term sequelae such as chronic fatigue.<ref>{{cite journal | vauthors = Hanevik K, Wensaas KA, Rortveit G, Eide GE, Mørch K, Langeland N | title = Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study | journal = Clinical Infectious Diseases | volume = 59 | issue = 10 | pages = 1394–400 | date = November 2014 | pmid = 25115874 | pmc = 4207419 | doi = 10.1093/cid/ciu629 }}</ref><ref>Quote: "for unclear reasons, chronic sequelae, including post-infectious irritable bowel syndrome, chronic fatigue [..], malnutrition [..], cognitive impairment [..], and extra-intestinal manifestations (such as food allergy, urticaria, reactive arthritis, and inflammatory ocular manifestations), can develop and possibly persist beyond detectable parasite shedding". Quoted from: {{cite journal | vauthors = Bartelt LA, Sartor RB | title = Advances in understanding Giardia: determinants and mechanisms of chronic sequelae | journal = F1000Prime Reports | volume = 7 | pages = 62 | year = 2015 | pmid = 26097735 | pmc = 4447054 | doi = 10.12703/P7-62 | type = Review }}</ref> The mechanism of transformation from cyst to trophozoites has not been |
Some intestinal parasitic infections may play a role in [[irritable bowel syndrome]]<ref>{{cite journal | vauthors = Stark D, van Hal S, Marriott D, Ellis J, Harkness J | title = Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis | journal = International Journal for Parasitology | volume = 37 | issue = 1 | pages = 11–20 | date = January 2007 | pmid = 17070814 | doi = 10.1016/j.ijpara.2006.09.009 }}</ref> and other long-term sequelae such as chronic fatigue.<ref>{{cite journal | vauthors = Hanevik K, Wensaas KA, Rortveit G, Eide GE, Mørch K, Langeland N | title = Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study | journal = Clinical Infectious Diseases | volume = 59 | issue = 10 | pages = 1394–400 | date = November 2014 | pmid = 25115874 | pmc = 4207419 | doi = 10.1093/cid/ciu629 }}</ref><ref>Quote: "for unclear reasons, chronic sequelae, including post-infectious irritable bowel syndrome, chronic fatigue [..], malnutrition [..], cognitive impairment [..], and extra-intestinal manifestations (such as food allergy, urticaria, reactive arthritis, and inflammatory ocular manifestations), can develop and possibly persist beyond detectable parasite shedding". Quoted from: {{cite journal | vauthors = Bartelt LA, Sartor RB | title = Advances in understanding Giardia: determinants and mechanisms of chronic sequelae | journal = F1000Prime Reports | volume = 7 | pages = 62 | year = 2015 | pmid = 26097735 | pmc = 4447054 | doi = 10.12703/P7-62 | type = Review | doi-access = free }}</ref> The mechanism of transformation from cyst to trophozoites has not been characterised<ref name=":4" /> but may be helpful in developing drug targets for treatment-resistant ''Giardia''. The interaction between ''Giardia'' and host immunity, internal flora, and other pathogens is not well understood.<ref name=Cot2011 />In vitro cell cultures have been widely used to study host-parasite interactions, and human enteroids are now being used as non-transformed intestinal epithelial cell infection models for G. intestinalis and other pathogens.<ref>{{Cite journal |last1=Grüttner |first1=Jana |last2=Rijn |first2=Jorik M. van |last3=Geiser |first3=Petra |last4=Florbrant |first4=Alexandra |last5=Webb |first5=Dominic-Luc |last6=Hellström |first6=Per M. |last7=Sundbom |first7=Magnus |last8=Sellin |first8=Mikael E. |last9=Svärd |first9=Staffan G. |date=2023-05-04 |title=Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection |journal=PLOS Pathogens |language=en |volume=19 |issue=5 |pages=e1011372 |doi=10.1371/journal.ppat.1011372 |issn=1553-7374 |pmc=10187934 |pmid=37141303 |doi-access=free }}</ref> |
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The main congress about giardiasis is the "International Giardia and Cryptosporidium Conference" (IGCC). A summary of results presented at the most recent edition (2019, in [[Rouen]], France) is available.<ref name="BuretCacciò2020">{{cite journal|last1=Buret|first1=André G.|last2=Cacciò|first2=Simone M.|last3=Favennec|first3=Loïc|last4=Svärd|first4=Staffan|title=Update on Giardia: Highlights from the seventh International ''Giardia'' and ''Cryptosporidium'' Conference|journal=Parasite|volume=27|year=2020|pages=49|issn=1776-1042|doi=10.1051/parasite/2020047|url= |pmid=32788035|pmc=7425178}} {{open access}}</ref> |
The main congress about giardiasis is the "International Giardia and Cryptosporidium Conference" (IGCC). A summary of results presented at the most recent edition (2019, in [[Rouen]], France) is available.<ref name="BuretCacciò2020">{{cite journal|last1=Buret|first1=André G.|last2=Cacciò|first2=Simone M.|last3=Favennec|first3=Loïc|last4=Svärd|first4=Staffan|title=Update on Giardia: Highlights from the seventh International ''Giardia'' and ''Cryptosporidium'' Conference|journal=Parasite|volume=27|year=2020|pages=49|issn=1776-1042|doi=10.1051/parasite/2020047|url= |pmid=32788035|pmc=7425178}} {{open access}}</ref> |
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==Other animals== |
==Other animals== |
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In both |
In both cats and dogs, giardiasis usually responds to metronidazole and fenbendazole. Metronidazole in pregnant cats can cause developmental malformations.<ref name=":9" /> Many cats dislike the taste of fenbendazole.<ref name=":9">{{Cite book|title=Cat Owner's Home Veterinary Handbook|last=Eldredge|first=Debra M.|publisher=Howell Book House|year=2008|pages=67}}</ref> Giardiasis has been shown to decrease weight in livestock.<ref name=Cot2011 /> |
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== References == |
== References == |
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* [https://www.cdc.gov/parasites/giardia/index.html Giardiasis Fact Sheet] |
* [https://www.cdc.gov/parasites/giardia/index.html Giardiasis Fact Sheet] |
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{{Medical condition classification and resources | DiseasesDB = 5213 |
{{Medical condition classification and resources | DiseasesDB = 5213 |
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| ICD11 = {{ICD11|1A31}} |
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| ICD10 = {{ICD10|A|07|1|a|00}} |
| ICD10 = {{ICD10|A|07|1|a|00}} |
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| ICD9 = {{ICD9|007.1}} |
| ICD9 = {{ICD9|007.1}} |
Revision as of 01:51, 29 August 2024
Giardiasis | |
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Other names | Beaver fever, giardia |
Giardia cell viewed with scanning electron microscope | |
Specialty | Infectious disease, gastroenterology |
Symptoms | Diarrhea, abdominal pain, weight loss, nausea[1] |
Usual onset | 1 to 3 weeks after exposure[2] |
Causes | Giardia duodenalis spread mainly through contaminated food or water[1] |
Risk factors | Hypogammaglobulinemia |
Diagnostic method | Stool testing[1] |
Differential diagnosis | Irritable bowel syndrome[1] |
Prevention | Improved sanitation[1] |
Treatment | Antiprotozoal medications |
Medication | Tinidazole, metronidazole[1] |
Frequency | Up to 7% (developed world), up to 30% (developing world)[1] |
Giardiasis is a parasitic disease caused by Giardia duodenalis (also known as G. lamblia and G. intestinalis).[3] Infected individuals who experience symptoms (about 10% have no symptoms) may have diarrhoea, abdominal pain, and weight loss.[1] Less common symptoms include vomiting and blood in the stool.[1] Symptoms usually begin one to three weeks after exposure and, without treatment, may last two to six weeks or longer.[4]
Giardiasis usually spreads when Giardia duodenalis cysts within faeces contaminate food or water that is later consumed orally.[1] The disease can also spread between people and through other animals.[1] Cysts may survive for nearly three months in cold water.[1] Giardiasis is diagnosed via stool tests.[1]
Prevention may be improved through proper hygiene practices.[1] Asymptomatic cases often do not need treatment.[1] When symptoms are present, treatment is typically provided with either tinidazole or metronidazole.[1] Infection may cause a person to become lactose intolerant, so it is recommended to temporarily avoid lactose following an infection.[1] Resistance to treatment may occur in some patients.[1]
Giardiasis occurs worldwide.[5] It is one of the most common parasitic human diseases.[3] Infection rates are as high as 7% in the developed world and 30% in the developing world.[1] In 2013, there were approximately 280 million people worldwide with symptomatic cases of giardiasis.[3] The World Health Organization classifies giardiasis as a neglected disease.[1] It is popularly known as beaver fever[6] in North America.
Signs and symptoms
Symptoms vary from none to severe diarrhoea with poor absorption of nutrients.[5] The cause of this wide range in severity of symptoms is not fully known but the intestinal flora of the infected host may play a role.[7][8] Diarrhoea is less likely to occur in people from developing countries.[7]
Symptoms typically develop 9–15 days after exposure,[9] but may occur as early as one day.[5] The most common and prominent symptom is chronic diarrhoea, which can occur for weeks or months if untreated.[10][11] Diarrhoea is often greasy and foul-smelling, with a tendency to float.[10][4] This characteristic diarrhoea is often accompanied by a number of other symptoms, including gas, abdominal cramps, and nausea or vomiting.[10][4] Some people also experience symptoms outside of the gastrointestinal tract, such as itchy skin, hives, and swelling of the eyes and joints, although these are less common.[4] Fever occurs in only about 15% of infected people,[12] despite the nickname "beaver fever".[6]
Prolonged disease is often characterised by diarrhoea and malabsorption of nutrients in the intestine.[10] This malabsorption causes fatty stools, substantial weight loss, and fatigue.[10] Additionally, those with giardiasis often have difficulty absorbing lactose, vitamin A, folate, and vitamin B12.[11][4] In children, prolonged giardiasis can cause failure to thrive and may impair mental development.[10][11] Symptomatic infections are well recognised as causing lactose intolerance,[13] which, though usually temporary, may become permanent.[14][15]
Cause
Giardiasis is caused by the protozoan Giardia duodenalis.[16] The infection occurs in many animals, including beavers, other rodents, cows, and sheep.[16] Animals are believed to play a role in keeping infections present in an environment.[16]
G. duodenalis has been sub-classified into eight genetic assemblages (designated A–H).[17] Genotyping of G. duodenalis isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main and possibly only G. duodenalis assemblages that infect humans.[17][18]
Risk factors
According to the United States Centers for Disease Control and Prevention (CDC), people at greatest risk of infection are:[19]
- People in childcare settings
- People who are in close contact with someone who has the disease
- Travellers within areas that have poor sanitation
- People who have contact with faeces during sexual activity
- Backpackers or campers who drink untreated water from springs, lakes, or rivers
- Swimmers who swallow water from swimming pools, hot tubs, interactive fountains, or untreated recreational water from springs, lakes, or rivers
- People who get their household water from a shallow well
- People with weakened immune systems
- People who have contact with infected animals or animal environments contaminated with faeces
Factors that increase infection risk for people from developed countries include changing nappies/diapers, consuming raw food, owning a dog, and travelling in the developing world.[1] However, 75% of infections in the United Kingdom are acquired in the UK, not through travel elsewhere.[1] In the United States, giardiasis occurs more often in summer, which is believed to be due to a greater amount of time spent on outdoor activities and travelling in the wilderness.[16]
Transmission
Giardiasis is transmitted via the faecal-oral route with the ingestion of cysts.[9] Primary routes are personal contact and contaminated water and food.[9] The cysts can stay infectious for up to three months in cold water.[16]
Many people with Giardia infections have no or few symptoms.[20] They may, however, still spread the disease.[20]
Pathophysiology
The life cycle of Giardia consists of a cyst form and a trophozoite form.[8] The cyst form is infectious and once it has found a host, transforms into the trophozoite form.[8] This trophozoite attaches to the intestinal wall and replicates within the gut.[8] As trophozoites continue along the gastrointestinal tract, they convert back to their cyst form which is then excreted with faeces.[1] Ingestion of only a few of these cysts is needed to generate infection in another host.[21]
Infection with Giardia results in decreased expression of brush border enzymes, morphological changes to the microvillus, increased intestinal permeability, and programmed cell death of small intestinal epithelial cells.[22] Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it.[23]
The attachment of trophozoites causes villous flattening and inhibition of enzymes that break down disaccharide sugars in the intestines.[7][22] Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhoea, one of the predominant symptoms.[22] In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases is highly varied.[citation needed]
The species Giardia intestinalis uses enzymes that break down proteins to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host T lymphocytes attack endothelial cells that have been injured in order to remove the cell.[7] This occurs after the disruption of proteins that connect brush border endothelial cells to one another.[22] The result is increased intestinal permeability.[22]
There appears to be a further increase in programmed enterocyte cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability.[22] There is significant upregulation of the programmed cell death cascade by the parasite, and, furthermore, substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax.[7] These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.[7]
Giardia protects its own growth by reducing the formation of the gas nitric oxide by consuming all local arginine, which is the amino acid necessary to make nitric oxide.[7] Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.[24]
Host defence
Host defence against Giardia consists of natural barriers, production of nitric oxide, and activation of the innate and adaptive immune systems.[citation needed]
Natural barriers
Natural barriers defend against the parasite entering the host's body. Natural barriers consist of mucus layers, bile salt, proteases, and lipases. Additionally, peristalsis and the renewal of enterocytes provide further protection against parasites.[25][26]
Nitric oxide production
Nitric oxide does not kill the parasite, but it inhibits the growth of trophozoites as well as excystation and encystation.[27][28]
Innate immune system
Lectin pathway of complement
The lectin pathway of complement is activated by mannose-binding lectin (MBL) which binds to N-acetylglucosamine. N-acetylglucosamine is a ligand for MBL and is present on the surface of Giardia.[29]
The classical pathway of complement
The classical pathway of complement is activated by antibodies specific against Giardia.[citation needed]
Adaptive immune system
Antibodies
Antibodies inhibit parasite replication and also induce parasite death via the classical pathway of complement.[citation needed]
Infection with Giardia typically results in a strong antibody response against the parasite. While IgG is made in significant amounts, IgA is believed to be more important in parasite control. IgA is the most abundant isotype in intestinal secretions, and it is also the dominant isotype in a mother's milk. Antibodies in a mother's milk protect children against giardiasis (passive immunisation).[30]
T-cells
The major aspect of adaptive immune responses is the T-cell response. Giardia is an extracellular pathogen. Therefore CD4+ helper T-cells are primarily responsible for this protective effect.[31]
One role of helper T-cells is to promote antibody production and isotype switching. Other roles include cytokine production (Il-4,IL-9) to help recruit other effector cells of the immune response.[31][32]
Diagnosis
- According to the CDC, detection of antigens on the surface of organisms in stool specimens is the current test of choice for diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques.[34]
- A trichrome stain of preserved stool is another method used to detect Giardia.[35]
- Microscopic examination of the stool can be performed for diagnosis.[1] This method is not preferred, however, due to inconsistent shedding of trophozoites and cysts in infected hosts.[1] Multiple samples over a period of time, typically one week, must be examined.[1]
- The Entero-Test uses a gelatin capsule with an attached thread. One end is attached to the inner aspect of the host's cheek, and the capsule is swallowed. Later, the thread is withdrawn and shaken in saline to release trophozoites which can be detected with a microscope. The sensitivity of this test is low, however, and is not routinely used for diagnosis.[36]
- Immunologic enzyme-linked immunosorbent assay (ELISA) testing may be used for diagnosis.[37] These tests are capable of a 90% detection rate or more.[37]
Although hydrogen breath tests indicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection.[38] Serological tests are not helpful in diagnosis.[1]
Prevention
The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water.[39]
Boiling water contaminated with Giardia effectively kills infectious cysts.[40] Chemical disinfectants or filters may be used.[41][42] Iodine-based disinfectants are preferred over chlorination as the latter is ineffective at destroying cysts.[43][44]
Although the evidence linking the drinking of water in the North American wilderness and giardiasis has been questioned, a number of studies raise concern.[45] Most if not all CDC verified backcountry giardiasis outbreaks have been attributed to water. Surveillance data (for 2013 and 2014) reports six outbreaks (96 cases) of waterborne giardiasis contracted from rivers, streams or springs[46] and less than 1% of reported giardiasis cases are associated with outbreaks.[47]
Person-to-person transmission accounts for the majority of Giardia infections, and is usually associated with poor hygiene and sanitation. Giardia is often found on the surface of the ground, in the soil, in undercooked foods, and in water, and on hands that have not been properly cleaned after handling infected faeces.[48] Water-borne transmission is associated with the ingestion of contaminated water. In the U.S., outbreaks typically occur in small water systems using inadequately treated surface water. Venereal transmission happens through faecal-oral contamination. Additionally, nappy/diaper changing and inadequate handwashing are risk factors for transmission from infected children. Lastly, food-borne epidemics of Giardia have developed through the contamination of food by infected food-handlers.[49]
Vaccine
There are no vaccines for humans yet, however there are several vaccine candidates in development. They are targeting: recombinant proteins, DNA vaccine, variant-specific surface proteins (VSP), cyst wall proteins (CWP), giadins and enzymes.[50] Researchers at CONICET have produced an oral vaccine after engineering customised proteins mimicking those expressed on the surface of Giardia trophozoites. The vaccine has proven effective in mice.[51][52]
At present, one commercially available vaccine exists – GiardiaVax, made from G. lamblia whole trophozoite lysate. It is a vaccine for veterinary use only in dogs and cats. GiardiaVax should promote production of specific antibodies.[53]
Treatment
Treatment is not always necessary as the infection usually resolves on its own.[7] However, if the illness is acute or symptoms persist and medications are needed to treat it, a nitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.[9]
The World Health Organisation and Infectious Disease Society of America recommend metronidazole as first line therapy.[54][55] The US CDC lists metronidazole, tinidazole, and nitazoxanide as effective first-line therapies;[56] of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA.[57][58][59] A meta-analysis published by the Cochrane Collaboration in 2012 found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues.[60] Other meta-analyses have reached similar conclusions.[61] Both medications need a five to ten day-long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole or nitazoxanide was felt to be of very low quality.[60] While tinidazole has side effects and efficacy similar to those of metronidazole, it is administered with a single dose.[20]
Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories.[21][62] The exact mechanism of resistance to all of these medications is not well understood.[62] In the case of nitroimidazole-resistant strains of Giardia, other drugs are available which have showed efficacy in treatment including quinacrine, nitazoxanide, bacitracin zinc, furazolidone and paromomycin.[20] Mepacrine may also be used for refractory cases.[21]
Probiotics, when given in combination with the standard treatment, have been shown to assist with clearance of Giardia.[63]
During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, resulting in less exposure to the foetus.[64] Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy.[20][65]
Prognosis
In people with a properly functioning immune system, infection may resolve without medication.[7] A small portion, however, develop a chronic infection.[7] People with an impaired immune system are at higher risk of chronic infection.[7] Medication is an effective cure for nearly all people although there is growing drug-resistance.[1][66][21]
Children with chronic giardiasis are at risk for failure to thrive as well as more long-lasting sequelae such as growth stunting.[67] Up to half of infected people develop a temporary lactose intolerance leading to symptoms that may mimic a chronic infection.[1] Some people experience post-infectious irritable bowel syndrome after the infection has cleared.[7] Giardiasis has also been implicated in the development of food allergies.[7] This is thought to be due to its effect on intestinal permeability.[7]
Epidemiology
In some developing countries Giardia is present in 30% of the population.[16] In the United States it is estimated that it is present in 3–7% of the population.[16] Giardiasis is associated with impaired growth and development in children, particularly influencing a country's economic growth by affecting Disability Adjusted Life Year (DALY) rates.[68][69]
The number of reported cases in the United States in 2018 was 15,584.[70] All states that classify giardiasis as a notifiable disease had cases of giardiasis.[70] The states of Illinois, Kentucky, Mississippi, North Carolina, Oklahoma, Tennessee, Texas, and Vermont did not notify the Center for Disease Control regarding cases in 2018.[70] There are seasonal trends associated with giardiasis.[71] July, August, and September are the months with the highest incidence of giardiasis in the United States.[72]
In the ECDC's (European Centre for Disease Prevention and Control) annual epidemiological report containing 2014 data, 17,278 confirmed giardiasis cases were reported by 23 of the 31 countries that are members of the EU/EEA.[73] Germany reported the highest number at 4,011 cases.[73] Following Germany, the UK reported 3,628 confirmed giardiasis cases. Together, this accounts for 44% of total reported cases.[73]
Research
Some intestinal parasitic infections may play a role in irritable bowel syndrome[74] and other long-term sequelae such as chronic fatigue.[75][76] The mechanism of transformation from cyst to trophozoites has not been characterised[8] but may be helpful in developing drug targets for treatment-resistant Giardia. The interaction between Giardia and host immunity, internal flora, and other pathogens is not well understood.[7]In vitro cell cultures have been widely used to study host-parasite interactions, and human enteroids are now being used as non-transformed intestinal epithelial cell infection models for G. intestinalis and other pathogens.[77]
The main congress about giardiasis is the "International Giardia and Cryptosporidium Conference" (IGCC). A summary of results presented at the most recent edition (2019, in Rouen, France) is available.[78]
Other animals
In both cats and dogs, giardiasis usually responds to metronidazole and fenbendazole. Metronidazole in pregnant cats can cause developmental malformations.[79] Many cats dislike the taste of fenbendazole.[79] Giardiasis has been shown to decrease weight in livestock.[7]
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