Giardia lamblia

Giardia lamblia

 

LIN, WEN-YANG (WESLEY), Ph.D

 

Giardia lamblia (=G. intestinalis, =G. duodenalis) also called Giardia duodenalis, Giardia intestinalis and pear-shaped flagellate is a common and well-known anaerobic flagellated protozoan parasites colonize in human (or in canine) small intestines and cause diarrhea, stomach pain etc. Its character of parasitic zoonoses make them also infecting other mammalian such as mice, rabbits, birds, reptiles and amphibians. Giardia lamblia prefer to live in cold water like rivers in mountains, cold springs and contaminated pools, which became the major cause of diarrhea in the US. Traveling in the developing world, dinning food without proper cooking, changing diapers etc. would be major risk factors of Giardiasis. The stool tests is the major diagnosis tool.

 

Discovery

In 1681, the Dutch scientist Antonie van Leeuwenhoek first found giardia through microscope. In 1915, Giardia lamblia was officially named after scientist Alfred Mathieu Giard who further studied it. In 2010, Andersson et al. has sequenced Giardia’s genome and discovered its ~5000 genes with 11.7 million base pair building blocks.

 

Cellular and physiological properties

Giardia is a diplomonad with two nuclei and duplicate organelles follow by four associated flagella and without cytostomes, Golgi apparatus and mitochondria. However, they have a mitochondrial remnant, mitosomes, which take part in the maturation of iron-sulfur proteins rather than ATP synthesis. The life cycle of Giardia lamblia consist of reproductive phase and resting phase that present two different forms: a swimming trophozoite and an infective cyst (Figure 1).

Genotyping of Giardia lamblia sub-classified eight genetic assemblages (from A to H). Among eight assemblages, A and B infect are the most dominate assemblages that infect wide range of species including human being. Various species of Giardia exist in different kind of hosts were identified by PCR or genetic tools include G. ardeae and G. psittaci from birds, G. agilis from amphibians, G. microti from voles and G. muris from other vertebrates.

Epidemiology

In 2013, WHO estimated that there were about 280 million people diagnosed with the Giardia infection around the world. The prevalence rate of Giardia in developed countries was 5% and over 20% among developing countries. In 2018, it present that 15,584 reported cases in 3–7% prevalence of the population in the US, especially high incidence in California, New York, Florida, and Wisconsin. Besides, the highest incidence months of giardiasis would be July, August, and September in the America. Furthermore, 23 of the 31 countries in the Europe had reported total 17,278 confirmed giardiasis cases in 2014. Thus, Giardiasis become one of the top 10 parasite diseases in human beings.

 

Risk factors

1. Travelers to countries where giardiasis is common.
2. Contacting contaminated drinking water, lakes or rivers, animals who have the disease.
3. Giardiasis often happened in the summer because of the higher activities rate in the wilderness.

 

Pathophysiology

Giardia exist in rivers, streams, wells and pools. It infect humans or animals by their contacting of contaminated foods, water, contaminated feces and sniffing unclean ground. It is reported that people (or pets) infected with Giardia may have no symptoms, but still spread the disease. Animals such as canines, cows, rodents, beavers, and sheep are also infecting targets of Giardia lamblia.

 

Figure1. The life cycle of Giardia lamblia

( http://www.dpd.cdc.gov/dpdx/images/ParasiteImages/G-L/Giardiasis/Giardia_LifeCycle.gif )

 

Giardia could transform between cyst form and trophozoite form. It spread and infect host by the cyst form that can remain contagious in cold water up to 3 months. After arriving intestines, Giardia stick to intestinal wall and colonize in the gut by altering its appearance into trophoziote form. Furthermore, they would recover back to cyst form when excreting out with stools. Giardia is spreading through fecal-oral route by animals’ contacting of contaminated water and food. It is one of the most common waterborne outbreaks of diarrhea in the America. Giardia spread between people and animals   (Figure 1).

 

When sojourning in the gastrointestinal tract with the trophoziote form, Giardia would engage in inhibiting of brush border enzymes that involved assimilation of disaccharide sugars, altering microvillus’ morphology that cause poor absorption of nutrients and water, triggering apoptosis of intestinal epithelial cells and enhancing intestinal permeability. Eventually, they would cause several clinical symptoms include diarrhea and intestinal malabsorption with or without histological changes.

 

For increasing intestinal permeability, Giardia lamblia would take several dedicated process such as assisting proliferation of crypt cells and using enzymes to degrade proteins on the villi of the brush border. The degraded proteins would likely lead to immunological recruitment and activation of host T lymphocytes on endothelial cells for removing injured cells. In addition, Giardia triggered cell apoptosis by downregulating of the anti-apoptotic Bcl-2 and upregulating of the proapoptotic Bax would facilitate breaking down intestinal barrier and enhancing permeability. They could also execute tactics of consuming all local arginine for decreasing the formation of the gas nitric oxide and protecting its own development.

 

Signs and symptoms

The parasitic disease caused from the infection of Giardia, called Giardiasis, also known as beaver fever. A 10% of Giardiasis can be temperate and showed no sign, which recovery by host’s immune function without extra treatments. Nevertheless, 90% infected hosts show apparent symptoms 2 days after infection and last 1 to 6 weeks. Giardia would make atrophy in the small intestinal villi that would lead to foul- smelling diarrhea and cause dehydration accompanied with malnutrition.

 

Diarrhea is the most common and dominant sign (in both humans and animals) accompanied by other symptoms include excess gas, abdominal cramps, abdominal pain, weight loss, nausea, vomiting, bloody feces and fever. However, only about 15% of infected hosts would occur fever. Most canines would be less active instead of exhibiting fever. Lesser common cases shows signs beyond intestinal system as itchy skin, hives and swelling of the eyes and joints. Medication should be administrated as soon as possible. Chronic diarrhea could last for weeks or months if untreated. Symptoms such as post-infectious irritable bowel syndrome, lactose intolerance and food allergies may occur and remain even if Giardia were dealt with medication.

 

Diagnosis

1. Detecting antigens in stool specimens, which is a sensitive and common choice for diagnosing giardiasis
2. Trichrome stain of fecal specimens. It generally stained fecal films for examining intestinal protozoa including Giardia.
3. The routine fecal flotation test with additional special zinc sulfate solution could reveal parasites on the specimen slides of the feces.
4. The enzyme-linked immunosorbent assay (ELISA) testing are about 90% accuracy of identifying G. lamblia.
5. Microscopic examination may present inconsistent result in examining trophozoites and cysts in infected hosts
6. The Entero-Test show low sensitivity in diagnosing G. lamblia. Besides, Serological tests are not suitable in detecting G. lamblia.
7. VETlabs Canine Parvovirus(CPV) Ag /Canine Coronavirus(CCV)/ Giardia Combo Test: Here we would like to recommend you a rapid reliable commercialized ICT test, VETlabs Canine Parvovirus(CPV) Ag /Canine Coronavirus(CCV)/ Giardia Combo Test, which can efficiently detect giardia in canine feces within 10 minutes (Figure 2).

 

Figure 2. A rapid reliable commercialized VETlabs Canine Parvovirus(CPV) Ag /Canine Coronavirus(CCV)/ Giardia Combo Test

( https://www.bioguard.com.tw/en/project/cpv-ag-ccv-ag-giardia-ag-combo-test/ )

 

Treatment

1. Canine:

Drugs:

Fenbendazole and metronidazole are the most common medication for eliminating Giardia in dogs. Medication are usually performed 3 to 10 days. If dogs occur refractory diarrhea, combined treatment of fenbendazole and metronidazole may be necessary.

 

Diet:

Once dehydration or severe diarrhea occurred, supportive treatment with highly digestible diet could take place alongside existing drugs.

 

Bathing:

Furthermore, owners should bath infected canines frequently to wash out Giardia cysts on their hairs.

 

2. Human:

Natural immunity:

People without symptoms do not always necessary need treatment as it usually resolves on its own.

Drugs:

Metronidazole is recommended as the first line drug for curing Giardiasis. Besides, nitroimidazole medication such as metronidazole, tinidazole, secnidazole or ornidazole will be used when symptoms is acute, go worse or persist; similarly, the anthelmintic drug albendazole would be used for killing Giardia sometimes. Nonetheless, albendazole may exist some side effects, including neurologic or gastrointestinal problems. Moreover, paromomycin and metronidazole are recommended during pregnancy.

Both nitroimidazoles and albendazole (but not nitazoxanide) show resistance issue on treating patients. The mechanism of causing resistance remain unclear. Other drugs such as quinacrine, nitazoxanide, bacitracin zinc, furazolidone, paromomycin and mepacrine are available when nitroimidazole-resistant occur.

 

Foods:

People might suffer lactose intolerant by giardia infection. Hence, milk is forbidden for a few weeks. In 2018, Lalle et al. suggest that taking probiotics in combination with conventional treatment would benefit on curing Giardiasis

 

Prevention

Most of the outbreaks of giardiasis are water-borne transmission, and the majority of infection cases are associated with poor sanitation. Thus improving hygiene is the prior consideration for preventing giardiasis.

 

References

1. Minetti C, Chalmers RM, Beeching NJ, Probert C, Lamden K (October 2016). “Giardiasis”(PDF). BMJ. 355: i5369. doi:1136/bmj.i5369. PMID 27789441.
2. “Parasites – Giardia”. CDC. 21 July 2015. Archivedfrom the original on 17 November 2016. Retrieved 17 November 2016.
3. “Giardiasis (beaver fever)”. New York State Department of Health. October 2011. Archived from the original on 11 May 2015. Retrieved 21 June 2015.
4. Esch KJ, Petersen CA (January 2013). “Transmission and epidemiology of zoonotic protozoal diseases of companion animals”. Clinical Microbiology Reviews. 26(1): 58–85. doi:1128/CMR.00067-12. PMC 3553666. PMID 23297259.
5. “Giardiasis”. cdc.gov. November 29, 2013. Archivedfrom the original on January 15, 2016. Retrieved 1 Jan 2016.
6. Cotton JA, Beatty JK, Buret AG (August 2011). “Host parasite interactions and pathophysiology in Giardia infections”. International Journal for Parasitology. 41(9): 925–33. doi:1016/j.ijpara.2011.05.002. PMID 21683702.
7. Einarsson E, Ma’ayeh S, Svärd SG (December 2016). “An up-date on Giardia and giardiasis”. Current Opinion in Microbiology. 34: 47–52. doi:1016/j.mib.2016.07.019. PMID 27501461.
8. Barry MA, Weatherhead JE, Hotez PJ, Woc-Colburn L (April 2013). “Childhood parasitic infections endemic to the United States”. Pediatric Clinics of North America. 60(2): 471–85. doi:1016/j.pcl.2012.12.011. PMID 23481112.
9. Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA. “III. Eukaryotic Parasites”. Parasitic Diseases (6 ed.). NY: Parasites Without Borders. pp. 11–17. Retrieved 11 July 2018.
10. Robertson LJ, Hanevik K, Escobedo AA, Mørch K, Langeland N (February 2010). “Giardiasis–why do the symptoms sometimes never stop?”. Trends in Parasitology. 26(2): 75–82. doi:1016/j.pt.2009.11.010. PMID 20056486.
11. “Giardia – Illness & Symptoms”. CDC. Retrieved 11 July2018.
12. Guerrant, Richard L.; Walker, David H.; Weller, Peter F. (2011). Tropical infectious diseases : principles, pathogens and practice(3rd ed.). Edinburgh: Saunders/Elsevier. p. 623. ISBN9781437737776. OCLC 722800379.
13. Pettoello Mantovani M, Guandalini S, Ecuba P, Corvino C, di Martino L (October 1989). “Lactose malabsorption in children with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation”. Journal of Pediatric Gastroenterology and Nutrition. 9 (3): 295–300. doi:1097/00005176-198910000-00006. PMID 2614615.
14. Wolfe MS (September 1975). “Giardiasis”. JAMA. 233(13): 1362–5. doi:1001/jama.233.13.1362. PMID 1174208.
15. Vega-Franco L, Meza C, Romero JL, Alanis SE, Meijerink J (1987). “Breath hydrogen test in children with giardiasis”. Journal of Pediatric Gastroenterology and Nutrition. 6(3): 365–8. doi:1097/00005176-198705000-00010. PMID 3430245.
16. Auerbach, Paul S. (2012). Wilderness medicine (6th ed.). Philadelphia, PA: Elsevier/Mosby. pp. Chapter 68. ISBN 9781437716788.
17. Heyworth MF (2016). “Giardia duodenalis genetic assemblages and hosts”. Parasite. 23: 13. doi:1051/parasite/2016013. PMC 4794627. PMID 26984116. Archived from the original on 2017-09-10.
18. Lalle M, Hanevik K (2018-10-24). “Treatment-refractory giardiasis: challenges and solutions”. Infection and Drug Resistance. 11: 1921–1933. doi:2147/idr.s141468. PMC 6207226. PMID 30498364.
19. CDC (July 15, 2015). “Sources of Infection & Risk Factors”. Parasites – Giardia. Archivedfrom the original on September 7, 2017.
20. Gardner TB, Hill DR (January 2001). “Treatment of giardiasis”. Clinical Microbiology Reviews. 14(1): 114–28. doi:1128/CMR.14.1.114-128.2001. PMC 88965. PMID 11148005.
21. Carter ER, Nabarro LE, Hedley L, Chiodini PL (January 2018). “Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions”. Clinical Microbiology and Infection. 24(1): 37–42. doi:1016/j.cmi.2017.05.028. PMID28624613.
22. Buret AG (September 2008). “Pathophysiology of enteric infections with Giardia duodenalius”. Parasite. 15(3): 261–5. doi:1051/parasite/2008153261. PMID 18814692.
23. Bartelt LA, Sartor RB (2015-05-26). “Advances in understanding Giardia: determinants and mechanisms of chronic sequelae”. F1000prime Reports. 7(62): 62. doi:12703/P7-62. PMC 4447054. PMID 26097735.
24. Muhkerjee, Sandeep. “Giardiasis”. Medscape Reference. Archived from the original on 17 November 2012. Retrieved 21 November 2012.
25. “Archived copy”. Archivedfrom the original on 2017-06-17. Retrieved 2017-09-09.
26. “Ova and Parasite Exam, Fecal (Immunocompromised or Travel History)”. Archivedfrom the original on 2014-10-29. Retrieved 2014-10-29.
27. Hooshyar H, Rostamkhani P, Arbabi M, Delavari M (2019). “Giardia lamblia infection: review of current diagnostic strategies”. Gastroenterology and Hepatology from Bed to Bench. 12(1): 3–12. PMC 6441489. PMID 30949313.
28. Rosenblatt JE, Sloan LM, Schneider SK (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): 337–41. doi:1016/0732-8893(93)90086-M. PMID 8495591.
29. Moya-Camarena SY, Sotelo N, Valencia ME (March 2002). “Effects of asymptomatic Giardia intestinalis infection on carbohydrate absorption in well-nourished Mexican children”. The American Journal of Tropical Medicine and Hygiene. 66(3): 255–9. doi:4269/ajtmh.2002.66.255. PMID 12139217.
30. “Parasites – Giardia, Prevention & Control”. Centers for Disease Control and Prevention. CDC. Archived from the original on 30 April 2015. Retrieved 26 April 2015.
31. “Emergency Disinfection of Drinking Water”. United State Envirinment Protection Agency. 2013-02-20. Archived from the original on 23 June 2015. Retrieved 21 June 2015. Retrieved 24 February 2011
32. Betancourt WQ, Rose JB (December 2004). “Drinking water treatment processes for removal of Cryptosporidium and Giardia”. Veterinary Parasitology. 126(1–2): 219–34. doi:1016/j.vetpar.2004.09.002. PMID 15567586.
33. Exner M, Gornik V (July 2004). “[Parasitic zoonoses transmitted by drinking water. Giardiasis and cryptosporidiosis]”. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz. 47(7): 698–704. doi:1007/s00103-004-0863-y. PMID 15254826.
34. Dunn, Noel; Juergens, Andrew L. (2019), “Giardiasis”, StatPearls, StatPearls Publishing, PMID 30020611, retrieved 2019-10-31
35. Ongerth JE, Johnson RL, Macdonald SC, Frost F, Stibbs HH (December 1989). “Back-country water treatment to prevent giardiasis”. American Journal of Public Health. 79(12): 1633–7. doi:2105/ajph.79.12.1633. PMC 1349767. PMID 2817191.
36. Julia E. Painter, PhD; Julia W. Gargano, PhD; Sarah A. Collier, MPH; Jonathan S. Yoder, MPH (2015). “Giardiasis Surveillance—United States, 2011–2012”. MMWR Supplements. 64(Suppl 3): 15–25. PMID 25928582. Retrieved 31 March 2018.
37. McClung RP, Roth DM, Vigar M, Roberts VA, Kahler AM, Cooley LA, et al. (November 2017). “Waterborne Disease Outbreaks Associated With Environmental and Undetermined Exposures to Water – United States, 2013-2014”. MMWR. Morbidity and Mortality Weekly Report. 66 (44): 1222–1225. doi:15585/mmwr.mm6644a4. PMC 5679586. PMID 29120997.
38. “Giardiasis Surveillance — United States, 2009–2010”. www.cdc.gov.
39. CDC Giardia 2011
40. Giardiasisat eMedicine
41. Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, et al. (February 2001). “Practice guidelines for the management of infectious diarrhea”(PDF). Clinical Infectious Diseases. 32 (3): 331–51. doi:1086/318514. PMID 11170940. Archived (PDF) from the original on February 10, 2016.
42. “Chapter 7.5.4 Continuing Diarrhoea | ICHRC”. www.ichrc.org. Archivedfrom the original on 2016-01-29. Retrieved 2016-01-09.
43. “Giardia: Treatment”. United States Centers for Disease Control and Prevention. 21 July 2015. Archivedfrom 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.
44. “Nitazoxanide Prescribing Information” (PDF). Romark Pharmaceuticals. August 2013. pp. 1–5. Archived from the original (PDF) on 16 January 2016. Retrieved 3 January 2016.
45. “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.
46. “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.
47. Granados CE, Reveiz L, Uribe LG, Criollo CP (December 2012). “Drugs for treating giardiasis”. The Cochrane Database of Systematic Reviews. 12: CD007787. doi:1002/14651858.cd007787.pub2. PMC6532677. PMID 23235648.
48. Solaymani-Mohammadi S, Genkinger JM, Loffredo CA, Singer SM (May 2010). Keiser J (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:1371/journal.pntd.0000682. PMC 2867942. PMID 20485492.
49. Leitsch D (2015-07-07). “Giardia lamblia”. Current Tropical Medicine Reports. 2(3): 128–135. doi:1007/s40475-015-0051-1. PMC 4523694. PMID 26258002.
50. Lalle, Marco; Hanevik, Kurt (2018-10-24). “Treatment-refractory giardiasis: challenges and solutions”. Infection and Drug Resistance. 11: 1921–1933. doi:2147/IDR.S141468. ISSN 1178-6973. PMC 6207226. PMID 30498364.
51. Farthing MJ (August 2006). “Treatment options for the eradication of intestinal protozoa”. Nature Clinical Practice. Gastroenterology & Hepatology. 3(8): 436–45. doi:1038/ncpgasthep0557. PMID 16883348.
52. Gardner TB, Hill DR (January 2001). “Treatment of giardiasis”. Clinical Microbiology Reviews. 14(1): 114–28. doi:1128/CMR.14.1.114-128.2001. PMC 88965. PMID 11148005.
53. Workowski KA, Bolan GA (June 2015). “Sexually transmitted diseases treatment guidelines, 2015”. MMWR. Recommendations and Reports. 64 (RR-03): 1–137. PMC 5885289. PMID 26042815.
54. Kasper, Dennis L.; Larry Jameson, J.; Hauser, Stephen L.; Loscalzo, Joseph; Fauci, Anthony S.; Longo, Dan L. (2015-04-08). Harrison’s principles of internal medicine. Kasper, Dennis L.,, Fauci, Anthony S., 1940-, Hauser, Stephen L.,, Longo, Dan L. (Dan Louis), 1949-, Jameson, J. Larry,, Loscalzo, Joseph (19th ed.). New York. ISBN9780071802154. OCLC 893557976.
55. Donowitz JR, Alam M, Kabir M, Ma JZ, Nazib F, Platts-Mills JA, et al. (September 2016). “A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea”. Clinical Infectious Diseases. 63(6): 792–7. doi:1093/cid/ciw391. PMC 4996141. PMID 27313261.
56. “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.
57. Painter, Julia E.; Gargano, Julia W.; Collier, Sarah A.; Yoder, Jonathan S. (2015-05-01). “Giardiasis surveillance — United States, 2011-2012”. MMWR Supplements. 64(3): 15–25. ISSN 2380-8942. PMID 25928582.
58. Jonathan S. Yoder, MPH; Julia W. Gargano, PhD; Ryan M. Wallace, DVM; Michael J. Beach, PhD (2012). “Giardiasis Surveillance-United States, 2009-2010”. Morbidity and Mortality Weekly Report. Surveillance Summaries. Centers of Disease Control and Prevention. 61(5): 13–23. PMID 22951494. Retrieved 30 November 2017.
59. “Giardiasis- Annual Epidemiological Report 2016”. European Centre for Disease Prevention and Control. European Centre for Disease Prevention and Control. 2017-01-30. Retrieved 30 November 2017.
60. 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”. International Journal for Parasitology. 37 (1): 11–20. doi:1016/j.ijpara.2006.09.009. PMID 17070814.
61. Hanevik K, Wensaas KA, Rortveit G, Eide GE, Mørch K, Langeland N (November 2014). “Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study”. Clinical Infectious Diseases. 59(10): 1394–400. doi:1093/cid/ciu629. PMC 4207419. PMID 25115874.
62. 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: Bartelt LA, Sartor RB (2015). “Advances in understanding Giardia: determinants and mechanisms of chronic sequelae”. F1000prime Reports(Review). 7: 62. doi:12703/P7-62. PMC4447054. PMID 26097735.
63. Eldredge, Debra M. (2008). Cat Owner’s Home Veterinary Handbook. Howell Book House. p. 67.
64. Hooshyar, H., Rostamkhani, P., Arbabi, M., & Delavari, M. (2019). Giardia lamblia infection: review of current diagnostic strategies. Gastroenterology and Hepatology from Bed to Bench, 12(1), 3.
65. Adam, R. D. (2001). Biology of Giardia lamblia. Clinical microbiology reviews, 14(3), 447-475.