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Giardiasis Overview

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Giardiasis Treatment




Author: Murat Hökelek, MD, PhD, Technical Consultant of Parasitology Laboratory, Associate Professor, Department of Clinical Microbiology, Ondokuz Mayis University Medical School, Turkey

Murat Hökelek is a member of the following medical societies: Turkish Society for Parasitology

Coauthor(s): Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital

Editors: Glenn J Fennelly, MD, MPH, Director, Division of Pediatric Infectious Diseases, Jacobi Medical Center; Associate Professor, Department of Pediatrics, Albert Einstein College of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Martin Weisse, MD, Program Director, Associate Professor, Department of Pediatrics, West Virginia University; Robert W Tolan Jr, MD, Chief of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center

Author and Editor Disclosure

Synonyms and related keywords: giardiasis, Giardia, Giardia lamblia, Giardia duodenalis, Giardia intestinalis, protozoal diarrhea, steatorrhea, malabsorption, lambliasis

Background

Giardia lamblia is a ubiquitous gastrointestinal protozoon that may be identified in individuals with asymptomatic colonization or acute or chronic diarrheal illness. Infection is recognized more commonly in children than in adults.

Giardia species are endemic in areas of the world that have poor sanitation. In developing countries, the disease is an important cause of morbidity, and water- and food-borne outbreaks are common. Because of the small inoculum of organisms necessary to cause infection, giardiasis is common in daycare center attendees and institutionalized patients in developed countries. G lamblia is a particularly significant pathogen for people with malnutrition, immunodeficiencies, or cystic fibrosis. Beavers may be an important reservoir host for G lamblia.

G lamblia is genetically heterogeneous, with 2 major genotypes (A and B). Some strains appear more biologically fit than other strains, a factor that is potentially important in disease pathogenesis. Studies indicate that G lamblia undergoes surface antigenic variation that is most likely stimulated by the host immune response or the intestinal mucosa.

High-risk groups for giardiasis include travelers to highly endemic areas, immunocompromised individuals, and certain sexually active homosexual men. Cyst passage rates as high as 20% have been reported among certain groups of sexually active homosexual men. These individuals were frequently symptomatic.

Pathophysiology

The mechanisms by which G lamblia causes diarrhea and intestinal malabsorption are probably multifactorial and not yet fully elucidated. Although the parasite appears to alter epithelial structure and function, leading to malabsorption, diarrhea can occur in individuals in the absence of obvious light microscopic changes in small intestinal structure. Also, marked or moderate partial villous atrophy in the jejunum can be observed in histologic sections from asymptomatic individuals who are infected. In addition to disrupting the mucosal epithelium, effects in the luminal may contribute to malabsorption and the production of diarrhea.

G lamblia trophozoites attach to the epithelium and distort microvilli at the site of attachment. The trophozoite has a convex dorsal surface and a flat ventral surface containing a disk, which is often referred to as the sucking or adhesive disk. The parasite has powerful adhesion, catching, and holding abilities with its disk. In the murine model of giardiasis, the ventral disk adhesion imprints are marked but less impressive than in the human small intestine. However, this direct injury is an unlikely cause of the more extensive reduction in microvillus surface area, the reduction in disaccharidase activities, and the more pronounced abnormalities of villous architecture.

Varying degrees of malabsorption of sugars (eg, xylose, disaccharides), fats, and fat-soluble vitamins (eg, vitamins A and E) may contribute to substantial weight loss. The histopathologic response to giardiasis varies and imperfectly correlates with the clinical symptoms.

G lamblia may release cytopathic substances that damage the intestinal epithelium. Giardia species contain thiol-dependent and thiol-independent proteinases, which may find substrates in the microvillus membrane. In addition, the surface mannose-binding lectin of G lamblia may contribute to epithelial damage. Whatever the mechanism by which G lamblia damages villous epithelial cells, the result consistently appears to be an increase in crypt length and crypt cell proliferation.

Genotypically diverse isolates of Giardia species may vary in their ability to produce morphologic changes in the small intestine epithelium and to impair fluid, electrolyte, and solute transport.

Frequency

United States

G lamblia is the parasite most commonly identified in stool specimens. The age-specific prevalence of giardiasis is highest in childhood and adolescence and begins to decline thereafter. Overall, the asymptomatic carriage rate of G lamblia is estimated to be 3-7%. The asymptomatic carriage rate in children may be as high as 20% in southern regions and in children younger than 36 months who attend daycare centers. Asymptomatic carriage may persist for several months. Many children with giardiasis are symptomatic, have been shown to spread the disease within their homes, and may contribute to high endemic rates in their communities.

  • The incidence is high among individuals who camp and backpack in mountainous Western states. Incidences of 30-40% have been reported in Europeans and North Americans traveling to certain parts of the former Soviet Union (1974).

International

Giardiasis occurs in temperate and tropical regions worldwide, and it continues to be the most frequently identified human protozoal enteropathogen. In the industrialized world, overall prevalence rates are 2-5%. In the developing world, G lamblia infects infants early in life. Prevalence rates of 15-20% in children younger than 10 years are common.

Mortality/Morbidity

Most infected individuals are asymptomatic, and most infections are self-limited. However, chronic infections marked by chronic diarrhea or steatorrhea and malabsorption can occur and may last from weeks to months.

  • Death is rare and usually occurs in malnourished children.
  • G lamblia has been implicated as the chief cause of growth retardation in infected children, even after other diarrhea-causing agents are controlled.
  • Giardiasis is not associated with mortality except in cases of extreme dehydration, primarily in infants. Morbidity is moderate and involves primary GI symptoms.

Race

No racial predilection exists.

Sex

Giardiasis is slightly more common in males than in females.

Age

All ages are affected. Infants and young children have an increased susceptibility to giardiasis, although infection is rare during the first 6 months of life in breastfed infants. Age-specific prevalence of giardiasis continues to rise through infancy and childhood and begins to decline only in adolescence.



History

Most individuals with G lamblia are probably asymptomatic. Giardiasis produces symptoms more often in children than in adults.

  • The incubation period from the time of ingestion of G lamblia cysts until the onset of symptoms is 1-2 weeks (average, 8 d).
  • Symptoms develop in an estimated 40-80% of infected children.
  • Clinical signs and symptoms
    • Diarrhea
    • Malaise, weakness
    • Abdominal distention
    • Flatulence
    • Abdominal cramps
    • Nausea
    • Malodorous, greasy stools
    • Anorexia
    • Weight loss
    • Vomiting
    • Low-grade fever (infrequent)
    • Various neurologic symptoms (eg, irritability, sleep disorder, mental depression, neuroasthenia)
    • Urticaria

Physical

Physical examination reveals no specific findings, although general abdominal tenderness may be present in children (see also History above).

Causes

Giardiasis is caused by G lamblia infection acquired by means of fecal-oral transmission; contaminated water ingestion; or, less commonly, contaminated food ingestion.



Crohn Disease
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Other Problems to be Considered

Other etiologies of small-intestinal diarrhea (eg, bacterial gastroenteritis, strongyloidiasis, viral diarrhea)
Celiac disease



Lab Studies

  • Stool examination for trophozoites or cysts is the traditional method for diagnosing giardiasis. Trophozoites may also be identified in the small intestine. Cysts are oval, measure 8-12 X 7-10 µm, and characteristically contain 4 nuclei. Trophozoites are pear-shaped, dorsally convex, flattened parasites with 2 nuclei and 4 pairs of flagella.
    • Fresh and persevered stool samples should be examined.
    • Motile trophozoites are best identified in a saline wet mount of fresh liquid stool obtained during the acute stages of illness. Trophozoites are usually not found in semiformed stool.
    • Cysts are best detected in fresh stools after iodine staining or preservation in 10% buffered formalin or polyvinyl alcohol, with subsequent trichrome or iron hematoxylin staining.
    • Concentration techniques using formalin ether or zinc sulfate flotation may increase the yield.
    • G lamblia is identified in 50-70% of patients after a single stool examination and in more than 90% after 3 stool examinations.
  • Antigen detection assays are available and often the tests of choice.
    • A variety of immunologic techniques have been used to detect Giardia-specific antigens in fecal specimens. The most common technique is monoclonal antibody–based capture enzyme-linked immunosorbent assay (ELISA).
    • An immunofluorescence assay is available for detecting Giardia and Cryptosporidium species.
  • Deoxyribonucleic acid (DNA) probes for Giardia species are available. DNA-based fecal detection assays are being developed.

Imaging Studies

  • Some patients with giardiasis have a nonspecific radiographic abnormality of the small intestine. These changes, which are reversible with therapy, include thickening and distortion of the mucosal folds of the duodenum and jejunum, hypersecretion, and hypermotility.

Other Tests

  • Alternate methods to directly obtain duodenal fluid are the Entero-Test or duodenal biopsy.
    • For the Entero-Test (ie, string test), patients swallow a gelatin capsule on a string, and the capsule is left in the duodenum for several hours or overnight.
    • Biopsy can be used to obtain touch preparations and tissue sections to identify G lamblia and other enteric pathogens.
    • Biopsy can also be used to visualize changes in histologic features.

Histologic Findings

Intestinal biopsy shows flattened, mild lymphocytic infiltration and trophozoites on the surface.



Medical Care

Treat children with acute or chronic diarrhea who manifest a failure to thrive, malabsorption, or other GI tract symptoms in whom Giardia organisms have been identified.

  • Generally, do not treat asymptomatic persons who excrete the organism, except to prevent household transmission (eg, from toddlers to pregnant women or to patients with hypogammaglobulinemia or cystic fibrosis) and to permit adequate treatment in individuals with possible G lamblia–associated antibiotic malabsorption who require oral antibiotic treatment for other infections.
  • Routine treatment of infected persons in highly endemic areas where water supplies continue to be contaminated is of questionable value because reinfection may readily occur.
  • Treat all infected persons who are in nonendemic areas.
  • Appropriate fluid and electrolyte management is critical, particularly in patients with large-volume diarrheal losses.

Consultations

Consultations with pediatric infectious disease specialists, parasitologists, and pediatric gastroenterologists are recommended.



Drug Category: Antiprotozoal agents

The 3 major classes of drugs that have proven benefit in the treatment of giardiasis are nitroimidazole derivatives, acridine dyes (eg, quinacrine), and nitrofurans (eg, furazolidone).

Although most experts recommend metronidazole and tinidazole as the drugs of choice because the brief treatment periods encourage good patient adherence, treatment failures occur in as many as 20% of cases. In posttreatment stool testing, treatment failure occurs when the parasite is probably resistant to metronidazole. Therefore, treatment with a second-line drug (eg, mepacrine, furazolidone) may be necessary.

The effectiveness of quinacrine is similar to that of nitroimidazole derivatives; however, it is less tolerated because of its adverse effects. These include the following: mild and transient headache, dizziness, and GI complaints (diarrhea, anorexia, nausea, abdominal cramps, vomiting [rare]), pleomorphic skin eruptions, and neuropsychiatric disturbances (nervousness, vertigo, irritability, emotional change, nightmares, transient psychosis).

Furazolidone is the least effective antigiardial drug, but it is widely used to treat children in the United States, partly because it is available as a suspension.

Drug NameMetronidazole (Flagyl)
DescriptionImidazole ring–based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).
Adult Dose250 mg PO tid for 5 d
Pediatric Dose15 mg/kg/d PO divided tid for 5 d; not to exceed 750 mg/d
ContraindicationsDocumented hypersensitivity; first trimester of pregnancy
InteractionsMay increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction may occur with ingested ethanol
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsDo not use during first trimester of pregnancy; adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Drug NameFurazolidone (Furoxone)
DescriptionPO anti-infective agent of the oxazolidine class used to treat bacterial or protozoal diarrhea and enteritis. May help in traveler's diarrhea, cholera, and bacteremic salmonellosis. Is bactericidal by interfering with several bacterial enzyme systems. Structurally similar to MAOIs and has MAOI activity. Approved by FDA in 1955.
Adult Dose100 mg tab or susp PO qid for 7-10 d
Pediatric Dose<1 month: Not recommended
>1 month: 5-8.8 mg/kg/d PO divided qid for 10 d; not to exceed 400 mg/d
ContraindicationsDocumented hypersensitivity; G-6-PD deficiency
InteractionsConcurrent use with ethanol can cause disulfiramlike reaction; effectiveness and adverse effects of levodopa can increase if used concomitantly; agitation, seizures, diaphoresis, fever, coma, or apnea can occur with concomitant meperidine; increased pressor effects expected if administered with sympathomimetics (can cause release of large amounts of norepinephrine); concurrent use with tricyclic antidepressants can produce hypertension, hyperpyrexia, seizures, tachycardia, and acute psychosis
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsStructurally similar to MAOIs and has MAOI activity; orthostatic hypotension and hypoglycemia may occur

Drug NameQuinacrine (Atabrine)
DescriptionIndicated to treat giardiasis and cestodiasis. Occasionally used to treat and suppress malaria.
Adult Dose100 mg PO tid for 5-7 d
Pediatric Dose7 mg/kg/d PO divided tid pc for 5 d; not to exceed 300 mg/d
ContraindicationsDocumented hypersensitivity; pregnancy; increases toxicity of primaquine (do not coadminister)
InteractionsNone reported
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsCaution in hepatic disease, alcoholism, or with known hepatotoxic drugs; periodically assess CBC count in prolonged therapy; if a severe blood disorder not attributable to the treated disease occurs, consider discontinuation; caution in G-6-PD deficiency; instruct patients receiving prolonged therapy to promptly report any visual disturbances and perform periodic complete ophthalmologic examinations

Drug NameAlbendazole (Albenza)
DescriptionPoorly absorbed from GI tract because of its low aqueous solubility. Concentrations negligible or undetectable in plasma because it is rapidly converted to the sulfoxide metabolite before reaching systemic circulation; systemic anthelmintic activity attributed to primary metabolite, albendazole sulfoxide; PO bioavailability appears to be enhanced when coadministered with a fatty meal (with estimated fat content of 40 g), as evidenced by higher (ie, <5-fold on average) plasma concentrations of albendazole sulfoxide compared to the fasted state.
Adult Dose400 mg PO qd for 5 d
Pediatric Dose15 mg/kg/d PO divided bid for 5 d
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration with carbamazepine may decrease effectiveness; dexamethasone, cimetidine, and praziquantel may increase toxicity
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsDiscontinue use if LFT levels increase significantly (resume when levels decrease to pretest values); abdominal pain, nausea, vomiting, diarrhea, dizziness, vertigo, fever, increased intracranial pressure, and alopecia may occur

Drug NameNitazoxanide (Alinia)
DescriptionInhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites. Elicits antiprotozoal activity by interfering with 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 Dose500 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: 500 mg PO bid for 3 d
ContraindicationsDocumented hypersensitivity
InteractionsTizoxanide (nitazoxanide metabolite) is >99.9% bound to plasma protein and may potentially increase toxicity of other highly plasma protein–bound drugs
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsMay cause abdominal pain, diarrhea, vomiting, or headache; administer with food; caution when coadministered with other highly plasma protein–bound drugs with narrow therapeutic indices

Drug NameTinidazole (Fasigyn, Tindamax)
DescriptionNitroimidazole 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.
Adult Dose2 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
ContraindicationsDocumented hypersensitivity; first trimester of pregnancy
InteractionsLimited 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
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsCarcinogenicity 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 in 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 half of recommended dose following dialysis



Further Inpatient Care

  • Monitor patients with severe malnutrition or dehydration. Rare associations with giardiasis include cholecystitis, arthritis, pancreatitis, retinal arteritis, and iridocyclitis.

Further Outpatient Care

  • Recommended consultations include those with a parasitologist, an infectious disease specialist, and a gastroenterologist.

Deterrence/Prevention

  • Infected persons and persons at risk should carefully wash their hands after they have any contact with feces. Careful handwashing is important, especially for caregivers of diapered infants in daycare centers, where diarrhea is common and carriers of Giardia organisms are numerous.
    • Chlorination, sedimentation, and filtration methods should be implemented to adequately purify public water supplies.
    • Effective chlorine inactivation of Giardia cysts in water requires an optimal chlorine concentration, water pH, turbidity, temperature, and contact time. These variables cannot be appropriately controlled in all municipalities, and they are particularly difficult to control in swimming pools.
  • Advise travelers to endemic areas to avoid eating uncooked foods that may have been grown, washed, or prepared with contaminated water.
  • Drinking water can be purified by using filtration (pore size, <1 µm) or by briskly boiling water for at least 5 minutes.
  • Chlorine or iodine water treatments are less effective than boiling or filtration, but they may be used as alternatives when other methods are not available.
  • Breastfeeding appears to protect infants from G lamblia infections.

Complications

  • Chronic illness and weight loss
    • Malabsorption syndrome in adults
    • Disaccharidase deficiency
  • Growth retardation

Prognosis

  • The prognosis is usually good.
  • Reinfection is possible.
  • Drug resistance has been observed in clinical experience.
  • The parasite persists in the stool, and the symptoms continue for weeks if giardiasis is untreated.

Patient Education

  • Personal hygiene education should emphasize methods to minimize person-to-person transmission, particularly in high-risk settings such as daycare centers and residential institutions.
  • Avoiding oral-anal and oral-genital sex can decrease venereal transmission of giardiasis.
  • For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education article, Giardiasis.



Medical/Legal Pitfalls

  • Failure to diagnosis giardiasis or to differentiate it from other possible diarrheal agents

Special Concerns

  • Giardiasis is a common cause of chronic diarrhea and associated with significant morbidity, especially in children.
  • If medical treatment is restricted, as in the first trimester of pregnancy, effective supportive treatment should be administered.
  • Reinfection or treatment failure can be treated with a second course of the same drug or with an alternative drug.
  • The potential development of later clinical infection or chronic disease is not rare in giardiasis.



Media file 1:  A Giardia lamblia cyst.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Photo



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Article Last Updated: May 19, 2006