Giardia cell, SEM
|Classification and external resources|
Giardiasis (popularly known as beaver fever) is a zoonotic parasitic disease caused by the flagellate protozoan Giardia lamblia (also sometimes called Giardia intestinalis and Giardia duodenalis). The giardia organism inhabits the digestive tract of a wide variety of domestic and wild animal species, as well as humans. It is one of the most common pathogenic parasitic infections in humans worldwide; in 2013, there were about 280 million people worldwide with symptomatic giardiasis.
Signs and symptoms
Symptoms vary from none to severe diarrhea with poor absorption of nutrients. It can result in weakness, loss of appetite, stomach cramps, vomiting, bloating, excessive gas, and burping. Symptoms typically develop 9–15 days after exposure, but may occur as early as one day.
Symptoms are caused by Giardia organisms infecting the cells of the duodenum and jejunum of the small intestine and blocking nutrient absorption. Most people are asymptomatic; only about a third of those infected exhibit symptoms. If the infection is not treated, these symptoms may last for six weeks or more.
Symptomatic infections are well recognized as causing lactose intolerance, which, while usually temporary, may become permanent. Although hydrogen breath tests indicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection. It has been suggested that these observations are explained by symptomatic giardia infection allowing for the overgrowth of other bacteria.
Giardiasis is caused by the protozoan Giardia lamblia. The infection occurs in many animals including beavers (hence its nickname), as well as cows, rodents, and sheep. Animals are believed to play a role in keeping infections present in an environment.
G. duodenalis has been sub-classified into eight genetic assemblages (designated A–H). 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 (or possibly only) G. duodenalis assemblages that undeniably infect humans.
According to the CDC, "Those at greatest risk are travelers to countries where giardiasis is common, people in child care settings, those who are in close contact with someone who has the disease, people who swallow contaminated drinking water, backpackers or campers who drink untreated water from lakes or rivers, people who have contact with animals who have the disease, and men who have sex with men."
In the Unites States, giardiasis occurs more often during the summer. This is believed to be due to a greater amount of time spent on outdoor activities and traveling in the wilderness.
Giardiasis is transmitted via the fecal-oral route with the ingestion of cysts. Primary routes are personal contact and contaminated water and food. The cysts can stay infectious for up to three months in cold water.
Not all Giardia infections are symptomatic, and many people can unknowingly serve as carriers of the parasite.
Giardia are flagellated protozoans that cause decreased expression of brush border enzymes, morphological changes to the microvillus, and programmed cell death of small intestinal epithelial cells. There is no invasion of giardia trophozoites, and small intestinal morphology may appear normal in light microscopy.
The attachment of trophozoites causes villus flattening and inhibition of enzymes that break down disaccharide sugars in the intestines. 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 diarrhea, one of the predominant symptoms. 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.
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. This occurs after the disruption of proteins that connect brush border endothelial cells to one another. The result is heavily increased intestinal permeability.
There appears to be a further increase in programmed cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability. 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. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.
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. Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.
- 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.
- A trichrome stain of preserved stool is another method used to detect giardia.
- Microscopic examination of the stool for motile trophozoites or for the distinctive oval G.lamblia cysts can be performed.
- The entero-test uses a gelatin capsule with an attached thread. One end is attached to the inner aspect of the patient'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.
- Immunologic enzyme-linked immunosorbent assay (ELISA) testing is now available. These tests are capable of a 90% detection rate or more.
- Because Giardia lamblia is difficult to detect, this often leads to a delay in diagnosis or misdiagnosis; several tests should be conducted over a one-week period.
The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water.
Boiling suspect water for one minute is the surest method to make water safe to drink and kill disease-causing microorganisms such as Giardia lamblia if in doubt about whether water is infected. Chemical disinfectants or filters may be used.
According to a review of the literature from 2000, there is little evidence linking the drinking of water in the North American wilderness and Giardia. The researcher notes that treatment of drinking water for Giardia may not be as important as recommended hand-washing in wilderness regions in North America. CDC surveillance data (for 2005 and 2006) reports one outbreak (6 cases) of waterborne giardiasis contracted from drinking wilderness river water in Colorado. However, less than 1% of reported giardiasis cases are associated with outbreaks.
Treatment is not always necessary as the infection usually resolves on its own. 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.
The World Health Organization and Infectious Disease Society of America recommend metronidazole as first line therapy. The US CDC lists metronidazole, tinidazole, and nitazoxanide as effective first-line therapies; of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA. A meta-analysis done by the Cochrane Collaboration found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues. Other meta-analyses have reached similar conclusions. Both medications need a five to 10 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. While tinidazole has similar side effects and efficacy to metronidazole, it is administered with a single dose.
Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories so is theoretically possible. The exact mechanism of resistance to all of these medications are not well understood. 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.
During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, and thus less exposure to the fetus. Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy.
- "Giardiasis (beaver fever)". New York State Department of Health. October 2011. Retrieved 21 June 2015.
- Esch KJ, Petersen CA (January 2013). "Transmission and epidemiology of zoonotic protozoal diseases of companion animals". Clin Microbiol Rev 26 (1): 58–85. doi:10.1128/CMR.00067-12. PMC 3553666. PMID 23297259.
- "Giardiasis". cdc.gov. November 29, 2013. Retrieved Jan 2016.
- Barry MA, Weatherhead JE, Hotez PJ, Woc-Colburn L (2013). "Childhood parasitic infections endemic to the United States". Pediatr Clin North Am 60 (2): 471–85. doi:10.1016/j.pcl.2012.12.011. PMID 23481112.
- Pettoello Mantovani M, Guandalini S, Ecuba P, Corvino C, di Martino L (1989). "Lactose malabsorption in children with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation". J. Pediatr. Gastroenterol. Nutr. 9 (3): 295–300. doi:10.1097/00005176-198910000-00006. PMID 2614615.
- Wolfe MS (1975). "Giardiasis". JAMA 233 (13): 1362–5. doi:10.1001/jama.233.13.1362. PMID 1174208.
- Vega-Franco L, Meza C, Romero JL, Alanis SE, Meijerink J (1987). "Breath hydrogen test in children with giardiasis". J. Pediatr. Gastroenterol. Nutr. 6 (3): 365–8. doi:10.1097/00005176-198705000-00010. PMID 3430245.
- Moya-Camarena SY, Sotelo N, Valencia ME (2002). "Effects of asymptomatic Giardia intestinalis infection on carbohydrate absorption in well-nourished Mexican children" (PDF). Am. J. Trop. Med. Hyg. 66 (3): 255–9. PMID 12139217.
- Tomkins AM, Wright SG, Drasar BS, James WP (1978). "Bacterial colonization of jejunal mucosa in giardiasis". Trans. R. Soc. Trop. Med. Hyg. 72 (1): 33–6. doi:10.1016/0035-9203(78)90294-8. PMID 635972.
- Cordingley, FT; Crawford, GP (1986). "Giardia infection causes vitamin B12 deficiency". Australian and New Zealand journal of medicine 16 (1): 78–9. doi:10.1111/j.1445-5994.1986.tb01127.x. PMID 3458451.
- Auerbach, Paul S. (2012). Wilderness medicine (6th ed.). Philadelphia, PA: Elsevier/Mosby. pp. Chapter 68. ISBN 9781437716788.
- Heyworth, Martin F. (2016). "Giardia duodenalis genetic assemblages and hosts". Parasite 23: 13. doi:10.1051/parasite/2016013. ISSN 1776-1042.
- CDC (July 15, 2015). "Sources of Infection & Risk Factors". Parasites – Giardia.
- Gardner, TB; Hill, DR (Jan 2001). "Treatment of giardiasis.". Clinical Microbiology Reviews 14 (1): 114–28. doi:10.1128/CMR.14.1.114-128.2001. PMID 11148005.
- Muhkerjee, Sandeep. "Giardiasis". Medscape Reference. Retrieved 21 November 2012.
- Rosenblatt, John E. (May–June 1993). "Evaluation of an enzyme-linked immunosorbent assay for the detection of Giardia lamblia in stool specimens". Diagnostic Microbiology and Infectious Disease 16 (4): 337–341. doi:10.1016/0732-8893(93)90086-M. PMID 8495591. Retrieved 28 February 2015.
- Center for Disease Control—Parasite division—Giardia
- "Parasites - Giardia, Prevention & Control". Centers for Disease Control and Prevention. CDC. Retrieved 26 April 2015.
- "Emergency Disinfection of Drinking Water". United State Envirinment Protection Agency. Retrieved 21 June 2015. Retrieved 24 February 2011
- Betancourt, WQ; Rose, JB (2004). "Drinking water treatment processes for removal of Cryptosporidium and Giardia". Veterinary parasitology 126 (1–2): 219–34. doi:10.1016/j.vetpar.2004.09.002. PMID 15567586.
- Exner, M; Gornik, V (2004). "Parasitic zoonoses transmitted by drinking water. Giardiasis and cryptosporidiosis". Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 47 (7): 698–704. doi:10.1007/s00103-004-0863-y. PMID 15254826.
- Welch TP (2000). "Risk of giardiasis from consumption of wilderness water in North America: a systematic review of epidemiologic data". International Journal of Infectious Diseases 4 (2): 100–3. doi:10.1016/S1201-9712(00)90102-4. PMID 10737847.
- Yoder, J; Roberts, V; Craun, GF; Hill, V; Hicks, LA; Alexander, NT; Radke, V; Calderon, RL; Hlavsa, MC; Beach, MJ; Roy, SL (Sep 12, 2008). "Surveillance for waterborne disease and outbreaks associated with drinking water and water not intended for drinking—United States, 2005–2006.". Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C: 2002) (Centers for Disease Control and Prevention, (CDC)) 57 (9): 39–62. PMID 18784643.
- Giardiasis Surveillance—United States, 2009–2010
- "Practice Guidelines for the Management of Infectious Diarrhea" (PDF). Clinical Infectious Diseases. January 30, 2001. PMID 11170940.
- "Chapter 7.5.4 Continuing Diarrhoea | ICHRC". www.ichrc.org. Retrieved 2016-01-09.
- "Giardia: Treatment". United States Centers for Disease Control and Prevention. 21 July 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. Retrieved 3 January 2016.
- "Metronidazole Prescribing Information" (PDF). United States Food and Drug Administration. Pfizer. June 2015. pp. 6–7. Retrieved 10 January 2016.
- "Tinidazole Prescribing Informatiuon" (PDF). United States Food and Drug Administration. Mission Pharma. May 2007. p. 1. Retrieved 10 January 2016.
- Granados, Carlos E; Reveiz, Ludovic; Uribe, Luis G; Criollo, Claudia P (2012-12-12). Drugs for treating giardiasis. John Wiley & Sons, Ltd. doi:10.1002/14651858.cd007787.pub2.
- Solaymani-Mohammadi, S; Genkinger, JM; Loffredo, CA; Singer, SM (May 11, 2010). Keiser, Jennifer, ed. "A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis". PLOS Neglected Tropical Diseases 4 (5): e682. doi:10.1371/journal.pntd.0000682. PMC 2867942. PMID 20485492.
- Leitsch, David (2015-07-07). "Drug Resistance in the Microaerophilic Parasite Giardia lamblia". Current Tropical Medicine Reports 2 (3): 128–135. doi:10.1007/s40475-015-0051-1. ISSN 2196-3045. PMC 4523694. PMID 26258002.
- Farthing, Michael JG (2005). "Treatment Options for the Eradication of Intestinal Protozoa". Nature Clinical Practice Gastroenterology & Hepatology 3: 436–445. doi:10.1038/ncpgasthep0557. Retrieved 21 June 2015.
- Gardner, Timothy B.; Hill, David R. (2001-01-01). "Treatment of Giardiasis". Clinical Microbiology Reviews 14 (1): 114–128. doi:10.1128/CMR.14.1.114-128.2001. ISSN 0893-8512. PMC 88965. PMID 11148005.
- Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
- Stark D, van Hal S, Marriott D, Ellis J, Harkness J (January 2007). "Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis". Int. J. Parasitol. 37 (1): 11–20. doi:10.1016/j.ijpara.2006.09.009. PMID 17070814.
- Kathleen Meyer, How to Shit in the Woods: An Environmentally Sound Approach to a Lost Art, Ten Speed Press (1989). A practical guide to wilderness waste disposal to prevent giardiasis.