AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Giardiasis is a major diarrheal disease found throughout the world. The flagellate protozoan Giardia lamblia, its causative agent, is the most commonly identified intestinal parasite in the United States and the most common protozoal intestinal parasite isolated worldwide.

Giardiasis usually represents a zoonosis with cross-infectivity between animals and humans. Giardia have been isolated from the stools of beavers, dogs, cats, rodents, sheep, and cattle.

Pathophysiology

Giardiasis is caused by ingestion of Giardia cysts, which retain viability in cold water for as long as 2-3 months. The infective dose is low in humans; 10-25 cysts are capable of causing clinical disease in 8 of 25 subjects. Ingestion of more than 25 cysts results in a 100% infection rate. After ingestion of cysts, excystation, trophozoite multiplication, and colonization of the upper small bowel occur. 

The exact pathophysiology of giardiasis is unclear. Postulated mechanisms include damage to the endothelial brush border, enterotoxins, immunologic reactions, and altered gut motility and fluid hypersecretion via increased adenylate cyclase activity. Adhesion of trophozoites to the epithelium has been demonstrated to cause increased epithelial permeability. Giardia-induced loss of intestinal brush border surface area, villus flattening, inhibition of disaccharidase activities, and eventual overgrowth of enteric bacterial flora appear to be involved in the pathophysiology of giardiasis but have yet to be causatively linked to the disease's clinical manifestations.

Most infections result from fecal-oral transmission or ingestion of contaminated water. Contaminated food is a less common etiology. Person-to-person spread is common, with 25% of family members with infected children themselves becoming infected.

Most infections are asymptomatic, and the attack rate for symptomatic infection in the natural setting varies from 5-70%. Giardia is found in healthy people in endemic areas and in asymptomatic carrier states with high numbers of cysts excreted in stools common.

Predisposing factors to symptomatic infection include hypochlorhydria, various immune system deficiencies, blood group A, and malnutrition. The incubation period averages 1-2 weeks, with a mean of 9 days. The average duration of symptoms in all ages ranges from 3-10 weeks.

Frequency

United States

Giardiasis is found throughout the United States. Carrier rates as high as 30-60% have been documented among children in day care centers, institutions, and on Native American reservations. Endemic infection occurs most commonly from July through October among children younger than 5 years and adults aged 25-39 years. Between 1964 and 1984, 90 outbreaks (24,000 cases) of giardiasis in the United States were linked epidemiologically to water. These outbreaks typically occurred in small water systems using untreated or inadequately treated surface water.

Most water-borne outbreaks in the United States have occurred in western mountain regions (Rocky Mountains, Sierra Nevada, Cascades) where giardiasis must be considered endemic. However, since water-borne giardiasis outbreaks have been reported in every region in the United States, the diagnosis must be considered anywhere in the country. Areas and populations with poor hygiene and close physical contact tend to have higher rates of infection. Venereal transmission has been reported among homosexuals through direct fecal-oral contamination.

International

Giardiasis is prevalent throughout the world. Giardia is one of the first enteric pathogens to infect infants in the developing world, with peak prevalence rates of 15-20% in children younger than 10 years.

A recent study demonstrated a Giardia infection rate of 19.6 per 100,000 population per year in Canada.¹ While the yearly incidence of the disease was stable, a significant seasonal variation was observed, with a peak in late summer to early fall, which correlates with the pattern found in the United States.¹

Giardiasis accounts for a relatively small percentage of traveler's diarrhea. It is more likely to be found as the cause of diarrhea that occurs or persists after returning home from travel to developing regions of the world due to its relatively long incubation period and persistent symptoms. Giardia has been identified as the causative agent in a large percentage of cases among travelers in the region of St. Petersburg, Russia, where tap water is the primary source.

Mortality/Morbidity

Giardiasis is not associated with mortality except in cases of extreme dehydration, primarily in infants. Morbidity is moderate and involves primarily GI symptoms.

Race

Giardiasis does not have any race predilection. Native American populations residing on reservations can have high carrier rates.

Sex

Males have been noted to be at higher risk for infection than females. A Canadian population study demonstrated infection rates of 21.2 per 100,000 per year versus 17.9 per 100,000 per year for males and females, respectively, resulting in a relative risk of 1.19.¹

Age

Giardiasis occurs in all ages but is most common in early childhood.

CLINICAL

Section 3 of 11  

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History

A broad spectrum of clinical syndromes may occur. The vast majority of symptoms are GI in nature.

• Gastrointestinal

• • A small number of persons develop abrupt onset of explosive, watery diarrhea, abdominal cramps, foul flatus, vomiting, fever, and malaise; these symptoms last 3-4 days before transition into the more common subacute syndrome.
  • Most patients experience a more insidious onset of symptoms, which are recurrent or resistant.
  • Stools become malodorous, mushy, and greasy. Watery diarrhea may alternate with soft stools or even constipation. Stools do not contain blood or pus because dysenteric symptoms are not a feature of giardiasis.
  • Upper GI symptoms, often exacerbated by eating, accompany stool changes or may be present in the absence of soft stools. These include upper and midabdominal cramping, nausea, early satiety, bloating, sulfurous belching, substernal burning, and acid indigestion.
• Constitutional symptoms
• • Anorexia, fatigue, malaise, and weight loss are common.
  • Weight loss occurs in more than 50% of patients and averages 10 pounds per person.
  • Chronic illness may occur with adults presenting with long-standing malabsorption syndrome and children with failure to thrive.
• Lactose intolerance
• Miscellaneous: Unusual presentations include allergic manifestations such as urticaria, erythema multiforme, bronchospasm, reactive arthritis, and biliary tract disease.

Physical

• Physical examination generally is unremarkable.
• Abdominal examination may reveal nonspecific tenderness without evidence of peritoneal irritation.
• Rectal examination should reveal heme-negative stools.
• In severe cases, evidence of dehydration or wasting may be present.

Causes

• Giardiasis is caused by the ingestion of infective cysts.
• Person-to-person transmission, often associated with poor hygiene and sanitation, is a primary means of infection.
• Diaper changing and inadequate hand washing are risk factors for transmission from infected children.
• Children attending day care centers, as well as day care workers, have a higher risk of infection secondary to fecal-oral transmission.
• Water-borne transmission is responsible for a significant number of epidemics in the United States, generally following ingestion of unfiltered surface water. Giardia was implicated in 90 waterborne outbreaks in the United States from 1964-1984, affecting 23,500 persons.
• Venereal transmission occurs through fecal-oral contamination.
• Food-borne epidemics have been reported, most commonly secondary to contamination by infected food-handlers.
• Pets frequently harbor Giardia in their GI tracts, but they are not thought to be a significant cause of outbreaks in humans.

DIFFERENTIALS

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Other Problems to be Considered

Amebiasis
Bacterial overgrowth syndromes
Crohn ileitis
Cryptosporidium enteritis
Irritable bowel syndrome
Celiac sprue
Topical sprue

WORKUP

Section 5 of 11  

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Lab Studies

• Stool examination  
• • At least 3 stools taken at 2-day intervals should be examined for ova and parasites.
  • Trophozoites may be found in fresh, watery stools but disintegrate rapidly. If the stool is not fresh or is semiformed to formed, trophozoites will not be found.
  • Cysts are passed in soft and formed stools. Fresh stool can be mixed with an iodine solution or methylene blue and examined for cysts on a wet mount. If not immediately examined, stool should be preserved in polyvinyl, alcohol, or a formalin preparation. Cyst passage is extremely variable, not related to clinical symptoms, and may lag behind the onset of symptoms by a week or more.
  • Trichrome stain is useful for identification of the cysts and trophozoites.
  • Cysts are smooth walled and oval, measuring 8-12 mm long and 7-10 mm wide. Iodine stains the cysts brown and accentuates their intracystic structures, especially their curved median bodies, axonemes, and nuclei. By focusing through the plane of the sample, 4 nuclei may be visualized, representing 2 daughter trophozoites. 
  • Trophozoites are leaf-shaped, measuring 9-21 mm long and 5-15 mm wide. Stained organisms have a characteristic facelike image with 2 nuclei and transversely placed median bodies.
  • Because many antibiotics, enemas, laxatives, and barium studies mask or cause the disappearance of parasites from the stools, microscopic examination should be postponed for 5-10 days following these interventions.
  • Fecal leukocytes should not be visualized in stool samples of patients with giardiasis.
• Stool antigen detection
• •  Several commercially available tests to detect Giardia antigen in the stool exist. These utilize either an immunofluorescent antibody (IFA) assay or a capture enzyme-linked immunosorbent assay (ELISA) against cyst or trophozoite antigens.
  • These tests have a sensitivity of 85-98% and a specificity of 90-100%.
  • While more sensitive than stool examination, these examinations are limited to the detection of Giardia; isolated use might result in missing an alternative or concurrent parasitic infection.
• Stool culture
• •  Stool cultures are not useful in making the diagnosis of giardiasis because the organism cannot reliably be grown from patient samples.
  • Stool cultures are beneficial in ruling out other pathogens as the cause of the patient's symptoms.
• Serum antibody detection
• •  ELISA assays for serum antibodies against Giardia are not readily available.
  • Because immunoglobulin G (IgG) levels remain elevated for long periods, they are not beneficial in making the diagnosis of acute giardiasis. Serum anti-Giardia immunoglobulin M (IgM) can be beneficial in distinguishing between acute infections and past infections.
• Complete blood cell count (CBC) generally is not useful in giardiasis because the white blood cell (WBC) count is normal and eosinophilia is not present. 

• 
  
  Giardia cyst.

  
  
  Giardia trophozoite.

Imaging Studies

• Imaging studies are not indicated in giardiasis.
• If an upper GI study is obtained, it may demonstrate a rapid transit time and nonspecific irregular thickening of the folds of the proximal small bowel.
• Barium studies should be avoided because they can interfere with stool ova and parasites (O & P) examinations.

Other Tests

• String test
• • The string test (Entero-test) consists of a gelatin capsule containing a nylon string with a weight attached to it.
  • The patient tapes one end of the string to his cheek and swallows the capsule.
  • After the gelatin dissolves in the stomach, the weight carries the string into the duodenum.
  • The string is left in place for 4-6 hours or overnight while the patient is fasting.
  • After removal, it is examined for bilious staining, which indicates successful passage into the duodenum.
  • The mucus from the string is examined for trophozoites in an iodine or saline wet mount or after fixation and staining.

Procedures

• Duodenal sampling 
• • Endoscopy may be used to obtain a duodenal aspirate or biopsy. While rarely necessary, duodenal biopsy may be the most sensitive test.
  • This has several benefits over the string test. An aspirate can be cultured to assess for overgrowth of the small intestine.
  • Other small bowel parasites, such as microsporidia and cryptosporidia, may be detected in biopsy samples.
  • Spruelike lesions, which may occur with giardiasis, can be detected with this technique.
  • Trophozoites may be difficult to recognize in biopsy samples.
  • While not readily available, specific anti-Giardia immunoperoxidase stains aid in the detection of the organisms.

TREATMENT

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Prehospital Care

• Prehospital care generally is neither required nor indicated.
• Patients who are severely dehydrated may benefit from the administration of intravenous crystalloid fluids by Emergency Medical Services (EMS) personnel.

Emergency Department Care

• ED care consists of restoration of volume status with oral hydration or intravenous crystalloid solution.
• If diagnosis is made in the ED, antimicrobial therapy should be instituted. A number of antibiotic regimens may be used.
• The medical provider should ensure that close contacts of the patient are also examined for giardiasis and treated, if positive.

Consultations

• Consultation generally is not necessary for giardiasis.
• Gastroenterology consultation is required if endoscopy is deemed necessary to make the diagnosis.

MEDICATION

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Metronidazole is the antimicrobial agent most commonly used in the treatment of giardiasis in the United States. It has a cure rate of 85-90%. The recommended adult dose is 250 mg PO tid for 5-7 days. 

Tinidazole is now approved in the United States and is considered a first-line agent outside the United States. The efficacy is reported at 90%, and it is believed to have fewer side effects than metronidazole. A common adverse effect is GI upset. The recommended adult dose is 2 g PO once; for children, the recommended dose is 50 mg/kg PO once.

Some drugs not available in the United States are considered effective therapeutic alternatives. Quinacrine achieves a cure rate of 90-95%. The most common adverse effects include nausea, vomiting, and abdominal cramping. Occasional yellow discoloration of the skin, urine, and sclerae may occur. The recommended adult dose is 100 mg PO tid for 5-7 d; for children, the recommended dose is 2 mg/kg PO tid for 5-7 d. This medication should not be used in patients with documented hypersensitivity to this medication or related products, those diagnosed with psoriasis, or those with a history of psychosis.

Paromomycin has been recommended for use in pregnancy because systemic absorption is low, but the cure rate is lower than with other agents.

Drug Category: Antimicrobial agents

Therapy must cover all likely pathogens in the context of the clinical setting.

Drug Name	Nitazoxanide (Alinia)
Description	Inhibits growth of Cryptosporidium parvum sporozoites and oocysts and G lamblia trophozoites. Elicits antiprotozoal activity by interfering with the pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism. Available as a 20-mg/mL oral susp.
Adult Dose	500 mg PO bid for 3 d
Pediatric Dose	<1 year: Not established 1-4 years: 100 mg (5 mL) PO q12h for 3 d with food 4-12 years: 200 mg (10 mL) PO q12h for 3 d with food >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Tizoxanide (nitazoxanide metabolite) is highly bound to plasma protein (>99.9%); therefore, use caution when coadministered with other highly plasma protein–bound drugs with narrow therapeutic indices
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	May cause abdominal pain, diarrhea, vomiting, or headache; administer with food

Drug Name	Paromomycin (Humatin)
Description	A poorly absorbed aminoglycoside, which may be considered for use in severe infection in pregnant patients. Most common adverse effects include nausea, increased GI motility, abdominal pain, and diarrhea.
Adult Dose	25-30 mg/kg PO tid for 7-10 d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; intestinal obstruction
Interactions	Nephrotoxic potential may increase with concurrent administration of other aminoglycosides, penicillins, cephalosporins, amphotericin B, and loop diuretics
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Because of narrow therapeutic index and toxic hazards associated with extended administration, do not use for long-term therapy; caution in renal failure, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Tinidazole (Tindamax)
Description	Nitroimidazole antiprotozoal agent. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known. Indicated to treat giardiasis in adults and children 3 y and older.
Adult Dose	2 g PO once with food
Pediatric Dose	<3 years: Not established >3 years: 50 mg/kg PO once with food; not to exceed 2 g/dose
Contraindications	Documented hypersensitivity; first trimester of pregnancy
Interactions	Limited data exist; interaction information based on experience with other nitroimidazole derivatives (ie, metronidazole); may prolong PT when coadministered with warfarin; avoid alcoholic beverages and preparations containing ethanol or propylene glycol during and 3 d following administration (may cause disulfiramlike reaction); may increase serum levels of lithium, phenytoin, cyclosporine, tacrolimus, and fluorouracil; CYP450 inducers (eg, phenobarbital, rifampin, phenytoin) may increase elimination; CYP450 inhibitors (eg, cimetidine, ketoconazole) may decrease elimination; concurrent administration with cholestyramine may decrease oral bioavailability; oxytetracycline may antagonize effect
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Carcinogenicity has been observed in mice and rats treated chronically with metronidazole (another nitroimidazole), although not observed with tinidazole, use cautiously; seizures and peripheral neuropathy have been reported; caution with history of blood dyscrasia; may cause metallic/bitter taste, nausea, anorexia, vomiting, weakness, fatigue, dizziness, or headache; if administered on day of hemodialysis, administer additional dose equivalent to one-half of recommended dose following dialysis

Drug Name	Furazolidone (Furoxone)
Description	A nitrofuran advocated as an alternative drug for children because it is available in a liquid suspension. Because it is only about 80% effective, patients need to be observed closely for relapse of infection. The most common adverse effects are GI upset and brown discoloration of urine.
Adult Dose	100 mg PO qid for 7-10 d
Pediatric Dose	6 mg/kg/d PO divided qid for 7-10 d
Contraindications	Documented hypersensitivity
Interactions	Increases levodopa blood concentrations and, thus, potential for toxicity; causes disulfiram reactions when taken with alcohol; toxicity of meperidine, paroxetine, fluoxetine, sertraline, trazodone, MAOIs, sympathomimetic amines, and tricyclic antidepressants increase when taken with furazolidone
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in G-6-PD deficiency when administering prolonged treatments; medication inhibits enzyme monoamine oxidase

FOLLOW-UP

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Further Outpatient Care

• Patients should be referred to a primary care physician for close follow-up care to ensure resolution of the infection.

Complications

• Development of chronic illness with weight loss
• Malabsorption syndrome in adults
• Failure to thrive in children

Prognosis

• Prognosis is generally excellent.
• Giardiasis is usually a self-limited acute disease, and several antibiotic agents are available with good efficacy rates to shorten the disease course.
• Untreated, giardiases lasts for weeks.

Patient Education

• Hikers and travelers: Surface water should be disinfected prior to ingestion by boiling, use of halogenating compounds such as chlorine, or through use of filtration devices.
• Household contacts: Emphasis should be placed on strict personal hygiene, such as careful hand washing after diapers are changed.
• Day care workers: Meticulous hygiene and careful hand washing should be used to reduce spread between children and to staff.
• Sexual contacts: Patients should be advised that oral-anal and oral-genital contact increase the risk of transmission.
• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article, Giardiasis.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to consider the diagnosis: A careful history should determine if the patient is at risk for having acquired an infection with G lamblia.
• Failure to recommend medical evaluation of close contacts of patients with confirmed giardiasis

Special Concerns

• Pregnant patients
• • No consistent recommendations exist for the treatment of pregnant patients because of the potential adverse effects of anti-Giardia agents on the fetus.
  • If possible, treatment should be avoided during the first trimester.
  • Mildly symptomatic women should have treatment delayed until after delivery.
  • If the patient is left untreated, adequate nutrition and hydration maintenance are paramount.
• Failed treatment
• • Documenting the continued presence of Giardia in patients who appear unresponsive to treatment is important.
  • A significant number of patients develop post-Giardia lactose intolerance and present with symptoms consistent with persistent infection. These patients usually improve with time and with the institution of a lactose-free diet.
  • If Giardia is present in the patient, a careful history should indicate whether this is a reinfection or a treatment failure. A second course of the same drug should be effective in reinfections, whereas the use of an alternative drug should be effective in true treatment failures.
  • Patients who fail repeated courses of treatment should be evaluated for hypogammaglobulinemia and may require combination therapy or chronic suppressive therapy.
• Asymptomatic infection: Therapy for asymptomatic individuals should be initiated if the risk of reinfection is low. This reduces the risk of transmission to others and the potential development of later clinical infection or chronic disease.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Giardia cyst.
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Media file 2:  Giardia trophozoite.
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REFERENCES

Section 11 of 11

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1. Laupland KB, Church DL. Population-based laboratory surveillance for Giardia sp. and Cryptosporidium sp. infections in a large Canadian health region. BMC Infect Dis. 2005;5:72. [Medline].
2. Adachi JA, Backer HD, DuPont HL. Infectious diarrhea from wilderness and foreign travel. In: Auerbach PS, ed. Wilderness Medicine: Management of Wilderness and Environmental Emergencies. 5^th ed. Mosby-Year Book; 2007:1439-1441.
3. Anderson VR, Curran MP. Nitazoxanide: a review of its use in the treatment of gastrointestinal infections. Drugs. 2007;67(13):1947-67. [Medline].
4. Benenson AS. Giardiasis. In: Control of Communicable Diseases Manual. Amer Public Health Assn: 1995:202-204.
5. Buret AG. Mechanisms of epithelial dysfunction in giardiasis. Gut. Mar 2007;56(3):316-7. [Medline].
6. Chalupka S. Tainted water on tap: what to tell patients about preventing illness from drinking water. Am J Nurs. Nov 2005;105(11):40-52; quiz 53. [Medline].
7. Cheng AC, McDonald JR, Thielman NM. Infectious diarrhea in developed and developing countries. J Clin Gastroenterol. Oct 2005;39(9):757-73. [Medline].
8. Hill DR. Giardiasis. Issues in diagnosis and management. Infect Dis Clin North Am. Sep 1993;7(3):503-25. [Medline].
9. Katz DE, Heisey-Grove D, Beach M, Dicker RC, Matyas BT. Prolonged outbreak of giardiasis with two modes of transmission. Epidemiol Infect. Oct 2006;134(5):935-41. [Medline].
10. Larson SC. Traveler's diarrhea. Emerg Med Clin North Am. Feb 1997;15(1):179-89. [Medline].
11. Muller N, von Allmen N. Recent insights into the mucosal reactions associated with Giardia lamblia infections. Int J Parsitol. 2005;35(13):1339-47. [Medline].
12. NIH Consensus Development Conference. Travelers' diarrhea. JAMA. May 10 1985;253(18):2700-4. [Medline].
13. Ochoa TJ, White AC Jr. Nitazoxanide for treatment of intestinal parasites in children. Pediatr Infect Dis J. Jul 2005;24(7):641-2. [Medline].
14. Payne CM, Fass R, Bernstein H, Giron J, Bernstein C, Dvorak K, et al. Pathogenesis of diarrhea in the adult: diagnostic challenges and life-threatening conditions. Eur J Gastroenterol Hepatol. Oct 2006;18(10):1047-51. [Medline].
15. Sanford JP, Gilbert DN, Sande MA. Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc; 1997:83.
16. Thom K, Forrest G. Gastrointestinal infections in immunocompromised hosts. Curr Opin Gastroenterol. Jan 2006;22(1):18-23. [Medline].
17. Troeger H, Epple HJ, Schneider T, Wahnschaffe U, Ullrich R, Burchard GD, et al. Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut. Mar 2007;56(3):328-35. [Medline].
18. Weitzel T, Dittrich S, Mohl I, Adusu E, Jelinek T. Evaluation of seven commercial antigen detection tests for Giardia and Cryptosporidium in stool samples. Clin Microbiol Infect. Jul 2006;12(7):656-9. [Medline].
19. Wittner M, Tanowitz HB. Intestinal parasites in returned travelers. Med Clin North Am. Nov 1992;76(6):1433-48. [Medline].

Article Last Updated: Feb 4, 2008