GiardiasisGiardiasis

Mitra Ranjbar M.D.Mitra Ranjbar M.D.

Associate Professor of Associate Professor of MedicineMedicine

• Giardia lamblia (also known as G. Giardia lamblia (also known as G. duodenalis or G. intestinalis) is a duodenalis or G. intestinalis) is a flagellated protozoan parasite which flagellated protozoan parasite which is one of the two most common is one of the two most common gastrointestinal parasites in the gastrointestinal parasites in the world.world.

• G. lamblia causes both epidemic and G. lamblia causes both epidemic and sporadic disease and is an important sporadic disease and is an important etiology of water-borne and food-etiology of water-borne and food-borne diarrhea, day-care center borne diarrhea, day-care center outbreaks, and diarrhea in outbreaks, and diarrhea in international travelers.international travelers.

• There are different strains of G. There are different strains of G. lamblia and antigenic variations lamblia and antigenic variations within single isolates, but the within single isolates, but the significance of this heterogeneity for significance of this heterogeneity for pathogenicity and the development pathogenicity and the development of immunity is unclear.of immunity is unclear.

LIFE CYCLE AND LIFE CYCLE AND PATHOGENESISPATHOGENESIS

• G. lamblia exists in two G. lamblia exists in two morphological forms: cysts and morphological forms: cysts and trophozoites. Cysts are the infectious trophozoites. Cysts are the infectious form of the parasite which can form of the parasite which can survive for prolonged periods in the survive for prolonged periods in the environment, if kept moist. environment, if kept moist.

• After ingestion, excystation occurs in After ingestion, excystation occurs in the upper small bowel to release the upper small bowel to release trophozoites, pear-shaped, trophozoites, pear-shaped, binucleate, multi flagellated binucleate, multi flagellated organisms that measure 9 to 15 µm organisms that measure 9 to 15 µm long, 5 to 15 µm wide, and 2 to 4 µm long, 5 to 15 µm wide, and 2 to 4 µm thick.thick.

• Trophozoites are the replicating form Trophozoites are the replicating form of the parasite, dividing by binary of the parasite, dividing by binary fission. Trophozoites possess an fission. Trophozoites possess an adhesive disk on the ventral surface adhesive disk on the ventral surface for attachment to the mucosal for attachment to the mucosal surface of the duodenum and surface of the duodenum and jejunum. jejunum.

• This form establishes residence in This form establishes residence in the proximal small bowel but does the proximal small bowel but does not invade or cause necrosis of the not invade or cause necrosis of the mucosal epithelium. For the mucosal epithelium. For the organism to persist in the infectious organism to persist in the infectious form, trophozoites must revert to form, trophozoites must revert to cysts, which occurs in the large cysts, which occurs in the large intestine. intestine.

• The pathogenesis of the diarrhea and The pathogenesis of the diarrhea and malabsorption that can occur in malabsorption that can occur in giardiasis is incompletely understood giardiasis is incompletely understood since Giardia are not invasive since Giardia are not invasive organisms. The major structural and organisms. The major structural and functional abnormalities associated functional abnormalities associated with giardiasis are found in the small with giardiasis are found in the small intestine. intestine.

• Human infection may be associated Human infection may be associated with a spectrum of light microscopic with a spectrum of light microscopic changes that range from no changes that range from no abnormalities, to mild or moderate abnormalities, to mild or moderate partial villous atrophy, to subtotal partial villous atrophy, to subtotal villous atrophy in severe cases. An villous atrophy in severe cases. An increase in crypt depth may also be increase in crypt depth may also be seen. seen.

• Even in the absence of changes in Even in the absence of changes in villous and crypt architecture, villous and crypt architecture, shortening and disruption of microvilli shortening and disruption of microvilli may occur. In addition to these may occur. In addition to these microscopic changes, deficiencies in microscopic changes, deficiencies in epithelial brush border enzymes (eg, epithelial brush border enzymes (eg, lactase) can develop. These alterations lactase) can develop. These alterations in epithelial structure and function in epithelial structure and function probably play a role in pathogenesis. probably play a role in pathogenesis.

• New cysts are passed back into the New cysts are passed back into the environment in feces. When patients environment in feces. When patients have diarrhea, trophozoites can also have diarrhea, trophozoites can also be found in the stool.be found in the stool.

EPIDEMIOLOGYEPIDEMIOLOGY

• G. lamblia is found worldwide. It is G. lamblia is found worldwide. It is especially common in areas where especially common in areas where there are poor sanitary conditions there are poor sanitary conditions and insufficient water treatment and insufficient water treatment facilities. facilities.

• In symptomatic individuals in the In symptomatic individuals in the developing world, the prevalence of developing world, the prevalence of Giardia has been reported to be as Giardia has been reported to be as high as 20 to 30 percent . High risk high as 20 to 30 percent . High risk groups include infants, young groups include infants, young children, travelers and the children, travelers and the immunocompromised. immunocompromised.

• Intestinal protozoa account for only Intestinal protozoa account for only one to three percent of acute one to three percent of acute traveler's diarrhea but for up to 30 traveler's diarrhea but for up to 30 percent of cases of chronic diarrhea.percent of cases of chronic diarrhea.

• Giardiasis is a frequent infectious Giardiasis is a frequent infectious cause of traveler's diarrhea lasting cause of traveler's diarrhea lasting more than two weeks. Attack rates are more than two weeks. Attack rates are particularly high after travel to parts of particularly high after travel to parts of the former Soviet Union, notably St. the former Soviet Union, notably St. Petersburg, which reportedly has had Petersburg, which reportedly has had hyperendemic levels of giardiasis over hyperendemic levels of giardiasis over the last few decades.the last few decades.

• Giardia infects animals including Giardia infects animals including dogs, cattle, and sheep. The role dogs, cattle, and sheep. The role these animals play in acting as a these animals play in acting as a reservoir for human disease is reservoir for human disease is unclear since molecular typing of unclear since molecular typing of various isolates indicates that many various isolates indicates that many animal parasites are not infectious in animal parasites are not infectious in humans.humans.

• Infection derives from fecally excreted Infection derives from fecally excreted cysts, which are immediately infectious cysts, which are immediately infectious when passed, unlike the oocysts of when passed, unlike the oocysts of Cyclospora. Ingestion of as few as 10 to Cyclospora. Ingestion of as few as 10 to 25 cysts can lead to giardiasis. 25 cysts can lead to giardiasis. Hypochlorhydria predisposes to Hypochlorhydria predisposes to infection; thus, previous gastric surgery infection; thus, previous gastric surgery or reduced gastric acidity are risk or reduced gastric acidity are risk factors for the acquisition of giardiasis. factors for the acquisition of giardiasis.

Routes of transmissionRoutes of transmission

• Three patterns of potential Three patterns of potential transmission of giardiasis are transmission of giardiasis are recognized : recognized :

• Person-to-person Person-to-person

• Food-borneFood-borne

• WaterborneWaterborne

•     Person-to-person transmission — Person-to-person transmission — Person-to-person transmission Person-to-person transmission accounts for the heightened accounts for the heightened prevalence of giardiasis in several prevalence of giardiasis in several settings. settings.

• Giardiasis can be endemic in Giardiasis can be endemic in institutions where there is fecal institutions where there is fecal incontinence and poor hygiene and incontinence and poor hygiene and can be an important source of can be an important source of intestinal infections in child care intestinal infections in child care centerscenters

• The risk of acquisition and The risk of acquisition and transmission is greatest for young transmission is greatest for young children who are not yet toilet children who are not yet toilet trained; such children can also serve trained; such children can also serve as a source for secondary cases as a source for secondary cases within their families.within their families.

• Person-to-person transmission is also Person-to-person transmission is also responsible for the prevalence of responsible for the prevalence of giardiasis among male homosexuals. giardiasis among male homosexuals. Anal intercourse was associated with an Anal intercourse was associated with an increased risk for the acquisition of increased risk for the acquisition of Giardia in a study of 100 patients Giardia in a study of 100 patients infected with the human infected with the human immunodeficiency virus (HIV); this immunodeficiency virus (HIV); this practice allows for the direct transfer of practice allows for the direct transfer of infectious cysts.infectious cysts.

•   Food-borne transmission — Cysts Food-borne transmission — Cysts are killed by cooking. Thus, food-are killed by cooking. Thus, food-borne spread occurs uncommonly borne spread occurs uncommonly and only when cysts contaminate and only when cysts contaminate food that is uncooked or after it has food that is uncooked or after it has been cooked.been cooked.

• Waterborne transmission — Water is Waterborne transmission — Water is a major source for the endemic or a major source for the endemic or epidemic spread of giardiasis. Deep epidemic spread of giardiasis. Deep well water is usually safe because well water is usually safe because filtration of water through soil filtration of water through soil removes Giardia cysts. removes Giardia cysts.

• In contrast, surface water, including In contrast, surface water, including mountain streams and municipal mountain streams and municipal reservoirs, can harbor Giardia cysts, reservoirs, can harbor Giardia cysts, which are hardy in cold water and which are hardy in cold water and resistant to routine levels of resistant to routine levels of chlorination. chlorination.

• In addition, water-dwelling In addition, water-dwelling mammals, such as beavers, can mammals, such as beavers, can become infected and may serve as become infected and may serve as continuing sources of water continuing sources of water contamination.contamination.

• It may be difficult to recognize a It may be difficult to recognize a water supply as the common source water supply as the common source of giardiasis because many who of giardiasis because many who become infected are asymptomatic become infected are asymptomatic or have few symptoms. or have few symptoms.

• Waterborne transmission accounts Waterborne transmission accounts for the acquisition of giardiasis by for the acquisition of giardiasis by many international travelers and for many international travelers and for the development of infection in those the development of infection in those who have been hiking or camping in who have been hiking or camping in wilderness areas. wilderness areas.

CLINICAL PRESENTATIONCLINICAL PRESENTATION

• A curious, and still unexplained, A curious, and still unexplained, feature of giardiasis is the varying feature of giardiasis is the varying severity of clinical disease that it can severity of clinical disease that it can cause. cause.

• A significant number of people with A significant number of people with giardiasis are asymptomatic, even giardiasis are asymptomatic, even following experimental infections following experimental infections with isolates derived from highly with isolates derived from highly symptomatic patients.symptomatic patients.

• As an example, in one well-studied As an example, in one well-studied outbreak of waterborne giardiasis, outbreak of waterborne giardiasis, two-thirds of those infected were two-thirds of those infected were asymptomatic. The spectrum of asymptomatic. The spectrum of clinical disease includes clinical disease includes asymptomatic infection, self-limited asymptomatic infection, self-limited acute giardiasis, and chronic acute giardiasis, and chronic infection. infection.

• The virulence of the giardial isolate, The virulence of the giardial isolate, the parasite load, the host immune the parasite load, the host immune response, and perhaps other host response, and perhaps other host determinants probably all contribute determinants probably all contribute the manifestations in an individual the manifestations in an individual patient. patient.

Asymptomatic infectionAsymptomatic infection

• Asymptomatic infection occurs in Asymptomatic infection occurs in approximately 60 percent of people approximately 60 percent of people exposed to Giardia and is seen in exposed to Giardia and is seen in both children and adults. both children and adults. Asymptomatic cyst carriage can last Asymptomatic cyst carriage can last over six months.over six months.

• Acute giardiasis — Acute giardiasis Acute giardiasis — Acute giardiasis occurs in less than half of people occurs in less than half of people infected with Giardia. Symptoms infected with Giardia. Symptoms include:include:

• Diarrhea that is sudden in onset and may be Diarrhea that is sudden in onset and may be initially watery — 90 percent initially watery — 90 percent

• Malaise — 85 percent Malaise — 85 percent • Foul-smelling and fatty stools (steatorrhea) — Foul-smelling and fatty stools (steatorrhea) —

70 percent 70 percent • Abdominal cramps and bloating — 70 percentAbdominal cramps and bloating — 70 percent• Flatulence — 75 percent Flatulence — 75 percent • Nausea — 70 percent Nausea — 70 percent • Weight loss — 65 percent Weight loss — 65 percent • Vomiting — 30 percentVomiting — 30 percent

• Fever occurs in only 10 to 15 percent Fever occurs in only 10 to 15 percent of patients and may be unrelated to of patients and may be unrelated to giardiasis. Symptoms usually develop giardiasis. Symptoms usually develop after an incubation period of one to after an incubation period of one to two weeks (range 1 to 45 days).two weeks (range 1 to 45 days).

• Distinguishing features of giardiasis Distinguishing features of giardiasis are the prolonged duration of are the prolonged duration of symptoms, often at least two to four symptoms, often at least two to four weeks, and the associated significant weeks, and the associated significant weight loss (10 percent of body weight loss (10 percent of body weight) that occurs in over 50 weight) that occurs in over 50 percent of cases.percent of cases.

• Clinical findings that have helped Clinical findings that have helped identify cases of giardiasis in identify cases of giardiasis in epidemiologic studies include a epidemiologic studies include a duration of illness lasting seven or duration of illness lasting seven or more days with at least two of the more days with at least two of the following six symptoms: diarrhea, following six symptoms: diarrhea, flatulence, foul-smelling stools, nausea, flatulence, foul-smelling stools, nausea, abdominal cramps, and excessive abdominal cramps, and excessive fatigue.fatigue.

Chronic giardiasisChronic giardiasis

• Chronic giardiasis may follow the Chronic giardiasis may follow the acute phase of illness or may develop acute phase of illness or may develop without an antecedent acute illness. In without an antecedent acute illness. In one study, 84 percent of one study, 84 percent of experimentally infected people self-experimentally infected people self-cured by a mean of 18.4 days following cured by a mean of 18.4 days following inoculation, while the remainder inoculation, while the remainder became chronically infected.became chronically infected.

• A chronic syndrome can develop in as A chronic syndrome can develop in as many as 30 to 50 percent of symptomatic many as 30 to 50 percent of symptomatic patients characterized by: patients characterized by:

• Loose stools but usually not diarrheaLoose stools but usually not diarrhea• Steatorrhea Steatorrhea • Profound weight loss Profound weight loss • Malabsorption Malabsorption • Malaise Malaise • Fatigue Fatigue • DepressionDepression

• Malabsorption is well documented and Malabsorption is well documented and may be responsible for the significant may be responsible for the significant weight loss that can occur in giardiasis weight loss that can occur in giardiasis (10 to 20 percent of body weight). (10 to 20 percent of body weight). Even when the infection is Even when the infection is asymptomatic, malabsorption of fats, asymptomatic, malabsorption of fats, sugars, carbohydrates and vitamins sugars, carbohydrates and vitamins may occurmay occur

• This can lead to vitamin deficiencies This can lead to vitamin deficiencies (A, B12), folate deficiency, (A, B12), folate deficiency, hypoalbuminemia, and especially hypoalbuminemia, and especially secondary lactase deficiency. secondary lactase deficiency.

• Acquired lactose intolerance occurs Acquired lactose intolerance occurs in up to 20 to 40 percent of cases in up to 20 to 40 percent of cases and can take many weeks to and can take many weeks to normalize even after clearance of the normalize even after clearance of the parasite. Clinically, this can lead to parasite. Clinically, this can lead to augmentation of intestinal symptoms augmentation of intestinal symptoms especially after the ingestion of milk especially after the ingestion of milk products.products.

ComplicationsComplications

• Studies about chronic giardiasis and Studies about chronic giardiasis and effects on growth and development effects on growth and development in children have yielded conflicting in children have yielded conflicting results. One prospective study in 45 results. One prospective study in 45 Guatemalan children suggested a Guatemalan children suggested a significant inverse relation between significant inverse relation between weight gain and increasing duration weight gain and increasing duration and severity of giardiasis.and severity of giardiasis.

• For a small number of patients, For a small number of patients, especially children, the persistence of especially children, the persistence of infection is associated with the infection is associated with the development of moderate to marked development of moderate to marked malabsorption and weight loss . malabsorption and weight loss . Chronic giardiasis may resemble other Chronic giardiasis may resemble other diseases associated with diseases associated with malabsorption , including inflammatory malabsorption , including inflammatory bowel disease.bowel disease.

• Occasionally, hypersensitivity Occasionally, hypersensitivity phenomena such as rash, urticaria, phenomena such as rash, urticaria, aphthous ulceration, and reactive aphthous ulceration, and reactive arthritis or synovitis are seen in arthritis or synovitis are seen in giardiasis, although these giardiasis, although these manifestations are rare. G. lamblia can manifestations are rare. G. lamblia can also uncommonly spread from the also uncommonly spread from the duodenum to the biliary and pancreatic duodenum to the biliary and pancreatic ducts. ducts.

• Cases of cholecystitis, cholangitis, Cases of cholecystitis, cholangitis, and granulomatous hepatitis due to and granulomatous hepatitis due to this pathogen have been reported. this pathogen have been reported. Impaired exocrine pancreatic Impaired exocrine pancreatic function with diminished secretion of function with diminished secretion of trypsin and lipase has been noted. trypsin and lipase has been noted.

DIAGNOSISDIAGNOSIS

• Nonspecific laboratory tests and Nonspecific laboratory tests and radiographic imaging are not useful radiographic imaging are not useful in diagnosing giardial infection. in diagnosing giardial infection. Patients with giardiasis do not have a Patients with giardiasis do not have a peripheral leukocytosis or peripheral leukocytosis or eosinophilia, and white cells are eosinophilia, and white cells are usually absent in stool specimens. usually absent in stool specimens.

• Fecal fat excretion and other Fecal fat excretion and other laboratory tests of malabsorption laboratory tests of malabsorption may be abnormal. An upper GI series may be abnormal. An upper GI series may demonstrate mucosal edema may demonstrate mucosal edema but often shows no significant but often shows no significant radiologic changes. radiologic changes.

Stool microscopyStool microscopy

• Most laboratories processing a stool Most laboratories processing a stool sample for ova and parasite (O&P) sample for ova and parasite (O&P) examination will divide the sample examination will divide the sample into portions. One part is examined into portions. One part is examined fresh mixed with saline to look for fresh mixed with saline to look for both trophozoites and cysts both trophozoites and cysts

• Other portions are placed in Other portions are placed in polyvinyl alcohol for permanent polyvinyl alcohol for permanent staining and/or in formalin for staining and/or in formalin for concentration which can increase the concentration which can increase the diagnostic yield. diagnostic yield.

• Substances such as barium, antacids, Substances such as barium, antacids, and mineral oil interfere with fecal and mineral oil interfere with fecal microscopic evaluations and should microscopic evaluations and should be postponed until stool be postponed until stool examinations for O&P are complete.examinations for O&P are complete.

• A loose watery stool is more likely to A loose watery stool is more likely to be positive for trophozoites, while a be positive for trophozoites, while a semiformed or formed stool will semiformed or formed stool will probably only contain cysts. Since probably only contain cysts. Since Giardia is excreted intermittently, it Giardia is excreted intermittently, it will be detected in 50 to 70 percent will be detected in 50 to 70 percent of cases with a single specimen and of cases with a single specimen and in 90 percent after three specimens.in 90 percent after three specimens.

ImmunoassaysImmunoassays

• A number of immunoassays have been A number of immunoassays have been developed to try to improve the ease and developed to try to improve the ease and sensitivity of diagnosis. These assays use sensitivity of diagnosis. These assays use antibodies directed against either cyst or antibodies directed against either cyst or trophozoite antigens. The different types of trophozoite antigens. The different types of kits available include: kits available include:

• Enzyme-linked immunosorbent assays Enzyme-linked immunosorbent assays (ELISA)(ELISA)

• Non-enzymatic immunoassays Non-enzymatic immunoassays

• The various assays have The various assays have demonstrated a sensitivity of 90 to demonstrated a sensitivity of 90 to 100 percent and a specificity of 95 to 100 percent and a specificity of 95 to 100 percent when compared to stool 100 percent when compared to stool microscopy.microscopy.

• One study of 325 stool specimens One study of 325 stool specimens showed that an ELISA against a showed that an ELISA against a specific Giardia antigen (antigen 65) specific Giardia antigen (antigen 65) was able to detect 30 percent more was able to detect 30 percent more cases of Giardia than stool O&P.cases of Giardia than stool O&P.

• Other studies that have compared Other studies that have compared results obtained using fecal results obtained using fecal specimens for O&P examination, specimens for O&P examination, direct immunofluorescent assay, and direct immunofluorescent assay, and immunodiagnostic techniques found immunodiagnostic techniques found that immunologic methods are more that immunologic methods are more sensitive and quicker than sensitive and quicker than conventional O&P methods.conventional O&P methods.

• Antigen assays have a similar cost to Antigen assays have a similar cost to O&P examinations. While more O&P examinations. While more sensitive than conventional sensitive than conventional microscopy for the diagnosis of microscopy for the diagnosis of Giardia, antigen testing should not Giardia, antigen testing should not replace the stool O&P for most replace the stool O&P for most patients with diarrhea. patients with diarrhea.

• The stool O&P examination can also The stool O&P examination can also reveal other pathogens and multiple reveal other pathogens and multiple parasites, which is particularly parasites, which is particularly important in returning travelers. important in returning travelers.

Duodenal aspirates or Duodenal aspirates or biopsiesbiopsies

• Duodenal sampling methods (eg, Duodenal sampling methods (eg, string test, duodenal aspiration or string test, duodenal aspiration or duodenal biopsy) are more invasive duodenal biopsy) are more invasive than the above diagnostic than the above diagnostic techniques.techniques.

• These tests are generally reserved These tests are generally reserved for confusing cases after noninvasive for confusing cases after noninvasive tests have been performed or for tests have been performed or for situations where small bowel situations where small bowel architecture needs to be examined.architecture needs to be examined.

• Small bowel biopsies of patients with Small bowel biopsies of patients with giardiasis can reveal a range of giardiasis can reveal a range of pathologic findings, but usually no pathologic findings, but usually no histopathologic abnormalities are histopathologic abnormalities are identified. identified.

SerologySerology

• Serologic tests are not of value in the Serologic tests are not of value in the diagnosis of acute giardiasis. IgG and diagnosis of acute giardiasis. IgG and IgM antibodies to the organism can be IgM antibodies to the organism can be demonstrated, but these antibodies demonstrated, but these antibodies persist after infection and thus are less persist after infection and thus are less helpful for establishing an etiology in the helpful for establishing an etiology in the individual symptomatic patient. individual symptomatic patient. However, serology is useful in However, serology is useful in epidemiologic studies. epidemiologic studies.

CultureCulture

• Giardia lamblia can be cultivated in Giardia lamblia can be cultivated in the laboratory, but this is only used the laboratory, but this is only used as a research tool. as a research tool.

Polymerase chain reactionPolymerase chain reaction

• Polymerase chain reaction (PCR) Polymerase chain reaction (PCR) diagnostic techniques are currently diagnostic techniques are currently only experimental. One study using only experimental. One study using PCR to detect Giardia in stool PCR to detect Giardia in stool samples showed that parasite samples showed that parasite concentrations as low as 10 concentrations as low as 10 parasites/100 uL of stool could be parasites/100 uL of stool could be detected.detected.

TREATMENTTREATMENT

• A number of drugs are available for A number of drugs are available for the treatment of giardiasis. But the the treatment of giardiasis. But the first question that should be first question that should be addressed is who requires treatment. addressed is who requires treatment.

Who should be treatedWho should be treated

• Since many patients are Since many patients are asymptomatic, it is not automatic asymptomatic, it is not automatic that all patients diagnosed with that all patients diagnosed with Giardia should receive antimicrobial Giardia should receive antimicrobial therapy. Any patient with symptoms therapy. Any patient with symptoms should be receive specific therapy. should be receive specific therapy.

• A reason for treating asymptomatic A reason for treating asymptomatic patients, particularly children, is to patients, particularly children, is to prevent spread of the infection. Thus, prevent spread of the infection. Thus, therapy is often given to children in therapy is often given to children in developed countries, especially those developed countries, especially those attending a day care center. attending a day care center.

• Children in developing countries are Children in developing countries are so likely to be reinfected within a short so likely to be reinfected within a short period of time that treatment is not period of time that treatment is not usually practical . All food handlers usually practical . All food handlers should be treated since they can should be treated since they can transmit infection. There is no need to transmit infection. There is no need to repeat a stool examination to check for repeat a stool examination to check for parasite clearance in individuals who parasite clearance in individuals who symptomatically improve. symptomatically improve.

AntimicrobialsAntimicrobials

• Metronidazole, although not Metronidazole, although not approved for the treatment of approved for the treatment of giardiasis by the Food and Drug giardiasis by the Food and Drug Administration (FDA), is the principal Administration (FDA), is the principal agent used to treat this infection.agent used to treat this infection.

• Metronidazole (250 mg PO TID for Metronidazole (250 mg PO TID for five days) has an efficacy of 80 to 95 five days) has an efficacy of 80 to 95 percent. Side effects include nausea, percent. Side effects include nausea, headache, and a metallic taste in the headache, and a metallic taste in the mouth; less commonly, dark urine, mouth; less commonly, dark urine, paresthesias, and dizziness occur. paresthesias, and dizziness occur.

• Metronidazole may have a Metronidazole may have a disulfiram-like effect, and alcohol disulfiram-like effect, and alcohol consumption should be avoided. consumption should be avoided. Isolates of Giardia with decreased Isolates of Giardia with decreased susceptibility to metronidazole have susceptibility to metronidazole have been described. been described.

• Tinidazole, a congener of Tinidazole, a congener of metronidazole, is highly effective for metronidazole, is highly effective for the treatment of giardiasis. A single 2 the treatment of giardiasis. A single 2 g dose (or 50 mg/kg for children) of g dose (or 50 mg/kg for children) of tinidazole has an efficacy of over 90 tinidazole has an efficacy of over 90 percent with few associated side percent with few associated side effects [65,66], and consequently effects [65,66], and consequently this is a practical alternative. this is a practical alternative.

• Quinacrine, the first effective drug Quinacrine, the first effective drug for giardiasis, is no longer distributed for giardiasis, is no longer distributed in the United States (although it is in the United States (although it is available from specific formulating available from specific formulating pharmacies). The recommended pharmacies). The recommended dose is 100 mg (2 mg/kg) three dose is 100 mg (2 mg/kg) three times daily for five days. times daily for five days.

• Newer agents that have been used for Newer agents that have been used for therapy include albendazole. therapy include albendazole. Albendazole (400 mg or 22.5 mg/kg PO Albendazole (400 mg or 22.5 mg/kg PO daily for 5 days) had an efficacy of 97 daily for 5 days) had an efficacy of 97 percent in children in Bangladesh. It percent in children in Bangladesh. It was also as effective as metronidazole was also as effective as metronidazole with fewer side effects in two other with fewer side effects in two other pediatric studies of giardiasis.pediatric studies of giardiasis.

• Furazolidone, a nitrofuran compound, is Furazolidone, a nitrofuran compound, is available as a suspension and is available as a suspension and is another alternative therapy. It is another alternative therapy. It is effective and well-tolerated, although effective and well-tolerated, although its efficacy is generally reported to be its efficacy is generally reported to be slightly lower than metronidazole slightly lower than metronidazole (approximately 80 percent). The (approximately 80 percent). The recommended dose is 100 mg (1.5 recommended dose is 100 mg (1.5 mg/kg) four times a day for 7 to 10 mg/kg) four times a day for 7 to 10 days. days.

• Nitazoxanide has been demonstrated to Nitazoxanide has been demonstrated to have equal or superior efficacy compared have equal or superior efficacy compared with metronidazole or mebendazole. It is with metronidazole or mebendazole. It is usually administered at a dose of 100 to usually administered at a dose of 100 to 500 mg twice daily for three days. A 500 mg twice daily for three days. A number of studies have shown this agent to number of studies have shown this agent to be at least as effective as metronidazole in be at least as effective as metronidazole in relieving symptoms in individuals with relieving symptoms in individuals with giardiasis, with efficacy ranging from 81 to giardiasis, with efficacy ranging from 81 to 85 percent.85 percent.

Drug choices in pregnancy Drug choices in pregnancy

• Treatment of giardiasis in pregnancy Treatment of giardiasis in pregnancy can be difficult. Metronidazole is can be difficult. Metronidazole is often avoided based upon old reports often avoided based upon old reports of teratogenic effects in rats, of teratogenic effects in rats, although human studies have not although human studies have not documented such risks.documented such risks.

• If symptoms of giardiasis are If symptoms of giardiasis are minimal, therapy can be withheld minimal, therapy can be withheld until after delivery. If symptoms are until after delivery. If symptoms are bothersome, paromomycin (25 to 35 bothersome, paromomycin (25 to 35 mg/kg per day PO in three divided mg/kg per day PO in three divided doses for seven days) can be used.doses for seven days) can be used.

• Paromomycin, a nonabsorbable Paromomycin, a nonabsorbable aminoglycoside, eliminates cysts in aminoglycoside, eliminates cysts in only 60 to 70 percent of patients , only 60 to 70 percent of patients , but it may provide symptomatic but it may provide symptomatic relief. relief.

• If giardiasis in pregnancy is associated If giardiasis in pregnancy is associated with dehydration, malabsorption, or with dehydration, malabsorption, or severe symptoms, therapy with severe symptoms, therapy with metronidazole is warranted. metronidazole is warranted. Malabsorptive symptoms may persist in Malabsorptive symptoms may persist in any patient receiving antiparasitic any patient receiving antiparasitic therapy since regeneration of therapy since regeneration of functioning intestinal mucosa requires functioning intestinal mucosa requires time. time.

Recurrence of symptoms Recurrence of symptoms

• Recurrent diarrhea following Recurrent diarrhea following treatment may be due to lactose treatment may be due to lactose intolerance rather than to recurrent intolerance rather than to recurrent or relapsed infection, so reevaluation or relapsed infection, so reevaluation of stool specimens should be of stool specimens should be undertaken before empiric undertaken before empiric retreatment is given. retreatment is given.

• Patients should be counseled to Patients should be counseled to avoid lactose-containing foods for avoid lactose-containing foods for one month after therapy.one month after therapy.

• If a patient has relapsed after therapy, If a patient has relapsed after therapy, either a second course of the original either a second course of the original agent or a different treatment can be agent or a different treatment can be administered. Options for treatment of administered. Options for treatment of refractory cases include: Longer repeat refractory cases include: Longer repeat courses or higher doses of the original courses or higher doses of the original agent. The dose of metronidazole, for agent. The dose of metronidazole, for example, can be increased to 750 mg example, can be increased to 750 mg PO TID for 10 days. PO TID for 10 days.

• Combination regimens can be used, Combination regimens can be used, such as metronidazole (or tinidazole) such as metronidazole (or tinidazole) plus quinacrine (usual dose plus quinacrine (usual dose metronidazole 250 mg TID plus metronidazole 250 mg TID plus quinacrine 100 mg for 14 to 21 quinacrine 100 mg for 14 to 21 days ) or albendazole plus days ) or albendazole plus metronidazole. metronidazole.

• This latter combination has been This latter combination has been reported to have 100 percent reported to have 100 percent efficacy in patients who had failed efficacy in patients who had failed standard metronidazole therapy.standard metronidazole therapy.

PREVENTIONPREVENTION

• Attention to hygiene is necessary to Attention to hygiene is necessary to prevent person-to-person prevent person-to-person transmission of giardiasis. (See transmission of giardiasis. (See "Travel advice"). Boiling or heating "Travel advice"). Boiling or heating water to at least 70ºC for 10 minutes water to at least 70ºC for 10 minutes eliminates Giardia cysts.eliminates Giardia cysts.

• For hikers and campers, iodine-For hikers and campers, iodine-based water treatments are more based water treatments are more efficacious than chlorine-based efficacious than chlorine-based treatments, but iodine disinfection treatments, but iodine disinfection must be carried out for at least eight must be carried out for at least eight hours.hours.

• High quality water filtration units are High quality water filtration units are also available and have proven also available and have proven effective for Giardia cyst removal.effective for Giardia cyst removal.

• Strict handwashing, care with diaper Strict handwashing, care with diaper disposal, and treatment of disposal, and treatment of symptomatic children can prevent symptomatic children can prevent the spread of giardiasis in day care the spread of giardiasis in day care centers. The treatment of centers. The treatment of asymptomatic infected children is asymptomatic infected children is more controversial.more controversial.

• Breast milk contains detectable Breast milk contains detectable titers of secretory IgA which is titers of secretory IgA which is protective for nursing infants; this protective for nursing infants; this protective mechanism is particularly protective mechanism is particularly important in developing countries . important in developing countries . No vaccine against this parasite is No vaccine against this parasite is available. available.