AUTHOR INFORMATION

Section 1 of 11

Authored by Andre Pennardt, MD, FACEP, Group Surgeon, Adjunct Assistant Professor of Military and Emergency Medicine, Group Medical Section, 10th Special Forces Group (Airborne)

Andre Pennardt, MD, FACEP, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Association of Military Surgeons of the US, International Society for Mountain Medicine, International Society of Travel Medicine, Special Operations Medical Association, and Wilderness Medical Society

Edited by Michelle Ervin, MD, Chair, Department of Emergency Medicine, Howard University Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Barry J Sheridan, DO, Chief, Department of Emergency Medical Services, Brooke Army Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center

Author's Email:	Andre Pennardt, MD, FACEP
Editor's Email:	Michelle Ervin, MD

eMedicine Journal, February 22 2006, VOLUME 7, Number 2

INTRODUCTION

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Background: Giardiasis is a major diarrheal disease found throughout the world. Giardia lamblia, its causative agent, is the most commonly identified intestinal parasite in the United States.

Pathophysiology: Giardiasis is caused by ingestion of Giardia cysts. The infective dose is low in humans; 10-25 cysts are capable of causing clinical disease. 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.

Frequency:

• In the US: 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.

• Internationally: 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. 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.

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

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

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.

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

CLINICAL

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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.

• The majority of 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 and poor hygiene are the primary means of infection.

• Giardiasis also may be contracted through the ingestion of contaminated water, a mechanism responsible for a significant number of epidemics in the United States. Giardia was implicated in 90 waterborne outbreaks in the United States from 1964-1984, affecting 23,500 persons.

• Venereal transmission occurs through direct fecal-oral transmission.

DIFFERENTIALS

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Gastroenteritis

Other Problems to be Considered:

Amebiasis
Bacterial overgrowth syndromes
Crohn ileitis
Cryptosporidium enteritis
Irritable bowel syndrome
Sprue, celiac
Sprue, topical

WORKUP

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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. 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 microns long and 7-10 microns wide. Iodine will stain the cysts brown and accentuate 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 microns long and 5-15 microns wide. Stained organisms have a characteristic facelike image with 2 nuclei and transversely placed median bodies.

• Since 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 giardiasis patients.

• 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 exams 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 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 and past infections.

• Complete blood count (CBC) generally is not useful in giardiasis because the white blood cell (WBC) count is normal and eosinophilia is not present.

Imaging Studies:

• Imaging studies are not indicated in giardiasis.

• If an upper GI study is ordered, 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) exams.

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.

• 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.

• Severely dehydrated patients 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 utilized.

• The medical provider should ensure that close contacts of the patient also are 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

Section 7 of 11

The only medications used in the treatment of giardiasis are antimicrobial agents to eradicate the organism in the bowel. Some drugs not available in the United States are considered effective therapeutic alternatives (eg, quinacrine [Atabrine]).

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, and 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.

Tinidazole is now approved in the United States and is considered a first-line agent in cases outside the United States. The efficacy is reported at 90%. 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.

Drug Category: Antimicrobial agents -- Therapy must cover all likely pathogens in the context of the clinical setting.

Drug Name	Metronidazole (Flagyl) -- A nitroimidazole commonly used as first-line agent in the United States with cure rates of 85-90%. High-dose short-course regimens have lower efficacy rates and should be avoided. Most common adverse effects include a metallic taste, nausea, dizziness, and headache.
Adult Dose	250 mg PO tid for 5-7 d
Pediatric Dose	5 mg/kg PO tid for 5-7 d
Contraindications	Documented hypersensitivity; relatively contraindicated in pregnancy, especially the first trimester
Interactions	May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Drug Name	Nitazoxanide (Alinia) -- 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 4-11 years: 200 mg (10 mL) PO q12h for 3 d with food >11 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 - Usually safe but benefits must outweigh the risks.
Precautions	May cause abdominal pain, diarrhea, vomiting, or headache; administer with food

Drug Name	Paromomycin (Humatin) -- 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 - Usually safe but benefits must outweigh the risks.
Precautions	Due to 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) -- 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 - Safety for use during pregnancy has not been established.
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) -- 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 - Safety for use during pregnancy has not been established.
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:

• Patient 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: These persons should be instructed in appropriate methods for disinfecting water prior to ingestion including boiling, use of halogenating compounds such as chlorine, and use of filtration devices.

• Household contacts: Emphasis should be placed on strict personal hygiene, such as frequent hand washing after diapers are changed.

• Sexual contact: Patients should be advised to avoid oral-anal and oral-genital contact to reduce the risk of venereal transmission.

• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article, Giardiasis.

MISCELLANEOUS

Section 9 of 11

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 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: Treatment 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.

TEST QUESTIONS

Section 10 of 11

CME Question 1: Which of the following is not a typical symptom of clinical giardiasis?

A: Abdominal cramping
B: General malaise
C: Bloody diarrhea
D: Weight loss
E: Flatulence

The correct answer is C: While giardiasis may present in a wide array of syndromes, dysenteric symptoms are not found with this infection.

CME Question 2: Which of the following techniques is least useful in making the diagnosis of acute giardiasis?

A: Examination of fresh stool for ova and parasites
B: Detection of Giardia antigen in the stool
C: String test
D: Serum assay for Giardia immunoglobulin G (IgG)
E: Duodenal biopsy

The correct answer is D: Serum IgG antibodies against Giardia remain elevated for long periods of time, making them less useful for the diagnosis of acute giardiasis, especially in endemic regions.

Pearl Question 1 (T/F): The most likely diagnosis in a hiker who presents with acute watery diarrhea and abdominal cramping 10 days after drinking stream water is amebiasis.

The correct answer is False: Infection with Giardia lamblia is the most likely diagnosis.

Pearl Question 2 (T/F): The most readily available test to diagnose giardiasis is stool examination for ova and parasites.

The correct answer is True: Examination of the stool for both ova and parasites is the most readily available test.

Pearl Question 3 (T/F): Giardiasis should be suspected in a patient presenting with chronic diarrhea (longer than 14 d).

The correct answer is True: Giardia lamblia is one of the leading causative agents of chronic diarrhea.

Pearl Question 4 (T/F): First-line antimicrobial agents that should be considered in US emergency departments for the treatment of giardiasis include metronidazole, quinacrine, and tinidazole.

The correct answer is False: Quinacrine is not available for the treatment of giardiasis in the United States.

BIBLIOGRAPHY

Section 11 of 11

• Benenson AS: Giardiasis. In: Control of Communicable Diseases Manual. Amer Public Health Assn; 1995: 202-204.
• Chalupka S: Tainted water on tap: what to tell patients about preventing illness from drinking water. Am J Nurs 2005 Nov; 105(11): 40-52; quiz 53[Medline].
• Cheng AC, McDonald JR, Thielman NM: Infectious diarrhea in developed and developing countries. J Clin Gastroenterol 2005 Oct; 39(9): 757-73[Medline].
• DuPont HL, Backer HD: Infectious Diarrhea from Wilderness and Foreign Travel. In: Auerbach PS, ed. Wilderness Medicine: Management of Wilderness and Environmental Emergencies, 3rd ed. Mosby-Year Book; 1995: 1048-1051.
• Hill DR: Giardiasis. Issues in diagnosis and management. Infect Dis Clin North Am 1993 Sep; 7(3): 503-25[Medline].
• Larson SC: Traveler's diarrhea. Emerg Med Clin North Am 1997 Feb; 15(1): 179-89[Medline].
• 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; 16: 72[Medline].
• 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].
• NIH Consensus Development Conference: Travelers' diarrhea. JAMA 1985 May 10; 253(18): 2700-4[Medline].
• Ochoa TJ, White AC: Nitazoxanide for treatment of intestinal parasites in children. Pediatr Infect Dis J 2005 Jul; 24(7): 641-2[Medline].
• Sanford JP, Gilbert DN, Sande MA: Sanford Guide to Antimicrobial Therapy. Antimicrobial Therapy, Inc; 1997: 83.
• Wittner M, Tanowitz HB: Intestinal parasites in returned travelers. Med Clin North Am 1992 Nov; 76(6): 1433-48[Medline].

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