Giardiasis
Giardiasis | |
---|---|
Other names | Beaver fever, giardia |
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
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
Giardiasis occurs worldwide. 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 people,[12] in spite of the nickname "beaver fever".[6]
Prolonged disease is often characterised by diarrhoea, along with malabsorption of nutrients in the intestine.[10] This malabsorption results in 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, while usually temporary, may become permanent.[14][15]
Cause
Giardiasis is caused by the
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
Transmission
Giardiasis is transmitted via the
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
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.
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
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
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
Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories.
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.
Epidemiology
In some
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] The states with the highest number of cases in 2018 were California, New York, Florida, and Wisconsin.[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]
References
- ^ S2CID 220092781.
- ^ "Giardia. General information". CDC. 21 July 2015. Archived from the original on 17 November 2016. Retrieved 17 November 2016.
- ^ PMID 23297259.
- ^ a b c d e "Giardia. Illness and symptoms". CDC. 26 February 2021. Retrieved 27 March 2022.
- ^ a b c "Giardiasis". cdc.gov. December 9, 2017. Archived from the original on April 14, 2021. Retrieved 27 March 2022.
- ^ a b "Giardiasis (beaver fever)". New York State Department of Health. January 2022. Archived from the original on 20 January 2022. Retrieved 27 March 2022.
- ^ PMID 21683702.
- ^ PMID 27501461.
- ^ PMID 23481112.
- ^ a b c d e f Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA. "III. Eukaryotic Parasites". Parasitic Diseases (6 ed.). NY: Parasites Without Borders. pp. 11–17. Archived from the original on 7 March 2020. Retrieved 11 July 2018.
- ^ PMID 20056486.
- OCLC 722800379.
- S2CID 32254397.
- PMID 1174208.
- S2CID 20733304.
- ^ ISBN 9781437716788.
- ^
- PMID 30498364.
- ^ CDC (July 15, 2015). "Sources of Infection & Risk Factors". Parasites – Giardia. Archived from the original on September 7, 2017.
- ^ PMID 11148005.
- ^ PMID 28624613.
- ^ PMID 18814692.
- PMID 26097735.
- ^ Muhkerjee, Sandeep. "Giardiasis". Medscape Reference. Archived from the original on 17 November 2012. Retrieved 21 November 2012.
- S2CID 7155680.
- ISBN 978-0-19-969782-3.
- PMID 10640765.
- PMID 16365445.
- PMID 20382117.
- S2CID 12621232.
- ^ PMID 10603384.
- PMID 15155662.
- PMID 34268030.
- "This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0." - ^ "Stool Specimens - Detection of Parasite Antigens". CDC. Archived from the original on 2017-06-17. Retrieved 2017-09-09.
- ^ "Ova and Parasite Exam, Fecal (Immunocompromised or Travel History)". Archived from the original on 2014-10-29. Retrieved 2014-10-29.
- PMID 30949313.
- ^ PMID 8495591.
- PMID 12139217.
- ^ "Parasites - Giardia, Prevention & Control". Centers for Disease Control and Prevention. CDC. Archived from the original on 30 April 2015. Retrieved 26 April 2015.
- ^ "Emergency Disinfection of Drinking Water". United States Environment Protection Agency. 2013-02-20. Archived from the original on 23 June 2015. Retrieved 21 June 2015. Retrieved 24 February 2011
- PMID 15567586.
- PMID 15254826.
- PMID 30020611, retrieved 2019-10-31
- PMID 2817191.
- PMID 25928582. Retrieved 31 March 2018.
- PMID 29120997.
- ^ "Giardiasis Surveillance — United States, 2009–2010". www.cdc.gov.
- ^ "Giardia". Parasites. Centers for Disease Control and Prevention. March 2011.
- ^ Giardiasis at eMedicine
- PMID 30962402.
- PMID 30664644.
- S2CID 198999660.
- PMID 32210953.
- (PDF) from the original on February 10, 2016.
- ^ "Chapter 7.5.4 Continuing Diarrhoea | ICHRC". www.ichrc.org. Archived from the original on 2016-01-29. Retrieved 2016-01-09.
- ^ "Giardia: Treatment". United States Centers for Disease Control and Prevention. 21 July 2015. Archived from the original on 24 December 2015. Retrieved 10 January 2016.
Several drugs can be used to treat Giardia infection. Effective treatments include metronidazole, tinidazole, and nitazoxanide1. Alternatives to these medications include paromomycin, quinacrine, and furazolidone1,2.
- ^ "Nitazoxanide Prescribing Information" (PDF). Romark Pharmaceuticals. August 2013. pp. 1–5. Archived from the original (PDF) on 16 January 2016. Retrieved 3 January 2016.
- ^ "Metronidazole Prescribing Information" (PDF). United States Food and Drug Administration. Pfizer. June 2015. pp. 6–7. Archived (PDF) from the original on 4 March 2016. Retrieved 10 January 2016.
- ^ "Tinidazole Prescribing Informatiuon" (PDF). United States Food and Drug Administration. Mission Pharma. May 2007. p. 1. Archived (PDF) from the original on 4 March 2016. Retrieved 10 January 2016.
- ^ PMID 23235648.
- PMID 20485492.
- ^ PMID 26258002.
- PMID 30498364.
- S2CID 19657328.
- PMID 26042815.
- )
- PMID 27313261.
- PMID 11432808.
- PMID 28883961.
- ^ a b c d "Table 2f. Annual reported cases of notifiable diseases, by region and reporting area - - United States and U.S. Territories, 2018". wonder.cdc.gov. Retrieved 2019-11-13.
- PMID 25928582.
- PMID 22951494. Retrieved 30 November 2017.
- ^ a b c "Giardiasis- Annual Epidemiological Report 2016". European Centre for Disease Prevention and Control. 2017-01-30. Retrieved 30 November 2017.
- PMID 17070814.
- PMID 25115874.
- PMID 26097735.
- PMID 37141303.
- PMID 32788035.
- ^ a b Eldredge, Debra M. (2008). Cat Owner's Home Veterinary Handbook. Howell Book House. p. 67.