Giardiasis

Giardiasis

Giardiasis in humans is caused by the infection of the small intestine by a single-celled organism called Giardia lamblia. Giardiasis occurs worldwide with a prevalence of 20–30%[1] in developing countries. Additionally, Giardia has a wide range of human and other mammalian hosts, thus making it very difficult to eliminate. The Centers for Disease Control and Giardiasis Prevention reports that in the US Giardia infects over 2.5 million people annually.

Agent and taxonomy

The disease causing agent of giardiasis is the enteric protozoan parasite Giardia Lamblia.

Cross referencing and synonyms:
G. intestinalis, G. duodenalis, Giardiasis, Giardia enteritis, Lambliasis, lamblia intestinalis, "beaver fever"[2]

Taxonomy and classification of G. lamblia

Kingdom: Protista
Subkingdom: Protozoa
Phylum: Sarcomastia
Subphylum: Mastigophora
Class: Zommastigophora
Order: Diplomonadida
Family: Hexamitidae
Genus: Giardia
Species: lamblia[3]

The phylogeny of Giardia is unclear. Because the organisms have simple intracellular structures, they might represent an early branching of eukaryotic lineage that diverges before the acquisition of mitochondria. Elucidating the taxonomy of giardia would significantly aid the understanding of eukaryotic evolution[4] In addition to G. lamblia, which is the only species found in humans,[5] other species of giardia have been identified. Distinction of giardia on the species level is controversial and difficult because of limited knowledge. Based on morphological difference, six species are named: G. lamblia (affects a wide range of mammals such as humans and livestock), G. agilis (affects amphibians), G. muris (affects rodents), G. ardeae and G. psittaci (affect birds), and G. microti (affects muskrats and voles). However, forty-one species can be named if species classification is based on host origins.[6] Recently, advances in molecular biology tools such as PCR have helped elucidate the genetic relationships among morphological identical "strains" of Giardia.[5]

Giardiasis Symptoms

A range of clinical syndromes may occur, with gastrointestinal syndromes being the most prevalent.
[edit] Gastrointestinal

A small number of infected individuals experience an abrupt onset of abdominal cramps, explosive, watery diarrhea, vomiting, foul flatus, and fever which may last for 3–4 days before proceeding into a more sub-acute phase. The majority of infected persons develop gradual symptoms that become recurrent or resistant.[12]

In both the acute and insidious onsets of symptoms, stools become greasy and malodorous but do not contain blood or pus because giardiasis does not involve dysenteric symptoms. Watery diarrhea may cycle with soft stools and constipation. Upper GI symptoms including nausea, early satiety, bloating, substernal burning, egg-smelling halitosis, and acid indigestion may be exacerbated by eating and are generally present in the absence of soft stools.[12]

Physical
Abdominal examination may expose nonspecific tenderness even if there is no sign of peritoneal irritation. Rectal examination should expose heme-negative stools and in severe cases, there may be evidence of dehydration.[12]

Giardiasis Diagnosis

Giardiasis is typically diagnosed by stool ova and parasites (commonly called O&P).[19]

It may be found on duodenal biopsies and is in the differential diagnosis of celiac disease.

Giardiasis Treatment

First line of treatment:

Metronidazole (Flagyl)
Adult dosage: 250 mg three times a day for 5 days[20]
Pediatric dosage: 15 mg per kilogram of body weight per dose, 3 times per day, for 5 days[20]
Side effects: Found in 7.1% of cases.[21] Include unpleasant metallic taste which might cause noncompliance in patients, GI discomfort such as vomiting, nausea, diarrhea, abdominal cramps, pancreatitis, vertigo, headache, CNS toxicity, transient leukemia, dizziness, drowsiness, lassitude, paraethesias, urticaria, and pruritis.[21] It causes mutation in salmonella and induces tumor in rodents,[21] but mutagenicity has never been observed in humans.[22]
Contraindication: Avoid alcohol while taking metronidazole. Metronidazole causes severe vomiting, headache, and GI discomfort by inhibiting aldehyde dehydrogenase, which breaks down alcohol.[22]
Additional drug facts: Metronidazole is a member of the family of nitroimidazoles, commercially known as Flagyl.[21] The tablets are quickly and completely absorbed by the small intestine[22] and found to have antigiardial effects on the trophozoites both in vivo and in vitro.[21] However, it is ineffective against cysts.[21] The drug is able to penetrate body tissues and could be found in saliva, breast milk, semen, and vaginal fluid.[22] It is metabolized in liver and secreted in urine.[22] Metronidazole targets trophozoites by forming active metabolites, which selectively inhibit DNA segregation in anaerobic protozoa such as giardia by DNA breakage and cross-linking.[21] It has minimal effects on host cells lining the intestinal lumen. Resistance is induced in laboratory and is correlated with decreased activity of parasite pyruvate.[22][23]

Tinidazole (Fasigyn)
Adult dosage: 2 g once[20]
Pediatric dosage: 50 mg per kilogram of body weight once (max. 2 g)[20]
Side effects: Side effects similar to metronidazole[21] but appears to be better tolerated and just as effective.[20] Common side effects include bitter taste, vertigo, and GI discomfort.[22] The drug should be taken with food to minimize side effects.[20]
Additional drug facts: Tinidazole was FDA approved. It is another member of the nitro-imidazole family. Health care providers recommend travelers (especially those traveling to Asian countries) buy the drug at the country of their destination and take it in an event of giardia infection.[22] The drug tablets can also be crushed and mixed with cherry syrup (Humco and others) for children. The syrup suspension can be kept at room temperature for 7 days and should be shaken before use.[20]

Nitazoxanide
Adult dosage: 500 mg two times a day for 3 days
Pediatric dosage: 1–3 yrs: 100 mg every 12 hours for 3 days[20]; 4–11 yrs: 200 mg every 12 hours for 3 days[20]
Side effects: A variety of side effects were reported but they occurred infrequently in all studies.[24] Studies failed to provide sufficiently similar results for a comprehensive analysis of the side effects of nitaxonzanide.[24] Some probable adverse effects include abdominal pain, dyspepsia, constipation, yellow discoloration of urine, dysuria and dry mouth, and dizziness.[24] The drug should be taken with food to minimize adverse effects.[20]
Additional drug facts: Nitazonxanide is FDA-approved as an oral suspension for treatment of giardiasis. It can be purchased in 500 mg tablets and in oral suspension.[20]

Alternative treatment

Paramomycin (Humatin)
Adult dosage: 25–35 mg per kilogram of body weight per dose, 3 doses per day for 7 days[20]
Pediatric dosage: 25–35 mg per kilogram of body weight per dose, 3 doses per day for 7 days[20]
Side effects: ototoxicity and nephrotoxicity with systemic administration[22]
Contraindication: Patients with impaired kidney function should use paramomycin with caution[22]
Additional drug facts: Paramomycin is a member of the aminoglycoside family.[21] It inhibits giardia protein synthesis by targeting the 50S and 30S ribosomal subunits.[22] Its activity in vitro is lower than nitroimidazoles; however, because it is poorly absorbed by small intestine, a higher concentration of the drug remains in the lumen to combat giadia organisms.[22] It is also the choice of drug to treat G. lamblia in resistant infection and during pregnancy.[22]

Furazolidone (Furoxone)
Adult dosage: 100 mg four times a day for 7–10 days[20]
Pediatric dosage: 6 mg per kilogram of body weight per dose, 4 doses per day for 7–10 days[20]
Side effects: Gastrointestinal symptoms (nausea, vomiting, diarrhea) are observed in 10% of patients. Other side effects include brown discoloration of urine, and hemolysis in G6PDH-deficient patients.[22]
Additional drug facts: it is a member of the nitrofuran family[21] penetrate body tissues and could be found in saliva, breast milk, semen and vaginal fluid.[22] Not recommended to treating pregnant patients because it has been shown to cause mammary tumor in rats and mutations in bacteria.[22]

Quinacrine
Adult dosage: 100 mg three times a day for 5 days[20]
Pediatric dosage: 2 mg per kilogram of body weight, three times per day for 5 days (max. 300 mg/d)[20]
Side effects: bitter taste and vomiting observed in 28% of study participants; yellow/orange discoloration of the skin, sclerae, and urine. Other common side effects include nausea, vomiting, headache, dizziness and fever. Drug induced psychosis has been observed but is very rare. Dermatitis and drug-induced retinopathy are also uncommon.[22] The drug also acts with lower efficacy in children because the drug has bitter taste and children are less compliant.[22]
Contraindication: Pregnant patients should avoid taking the drug because quinacrine can cross placenta and it might cause spina bifida and renal agenesis in the infant.[22]
The drug, unlike metronidazole, also target cysts.
This drug cannot be obtained commercially.[citation needed]

Albendazole (Albenza)
Adult dosage: 400 mg once a day for 5 days[22]
Pediatric dosage: 15 mg per kilogram of body weight per day for 5 to 7 days (max. 400 mg)[22]

Mebendazole (Vermox)
Adult dosage: 200–400 mg per day for 5 to 10 days[22]
Side effects for Albendazole and Mebendazole: common side effects include anorexia and constipation. Rare side effects include reversible neutropenia and elevated liver function tests. Whether they are terotogenic is unclear[22]
Contraindication of Albendazole and Mebendazole: Albendazole should be taken with caution for pregnant patients because there is a possibility that it might induce tumors. However, animal studies did not reveal increased incidences of cancer.[22]
Additional drug facts: Albendazole and Mebendazole are members of the benzimidazole family. They target G. lamblia by binding to β-tubulin and stopping cytoskeletal formation. It also interferes with glucose uptake of the organism.[22]

Lab diagnosis

Stool examination
3 stools taken at 2-day intervals are examined for ova and parasites. The cysts are detected 50–70% of the time in the first stool specimen examined, and 90% of the time the cysts are detected after 3 stool specimen examinations.[12]
Trophozoites disintegrate rapidly outside of the body but may be found in fresh, watery stools.
Cysts are found in soft and (semi)formed stools. Cyst passage is variable and not related to clinical symptoms. If not fresh, stool should be preserved in polyvinyl, alcohol, or a formalin. Cyst passage may fall behind the onset of symptoms by a week+
Trichrome stain is useful for finding the cysts and trophozoites.
Cysts are smooth walled and oval, measuring 8–12 μm long and 7–10 μm wide. Iodine stains the cysts brown and accentuates their intracystic structures, especially their curved median bodies, axonemes, and nuclei. (4 nuclei representing 2 daughter trophozoites).
Trophozoites are leaf-shaped, measuring 9–21 μm long and 5–15 μm wide. Stained organisms have a characteristic facelike image with 2 nuclei

Stool antigen detection
Commercially available tests use either an immunofluorescent antibody (IFA) assay or a capture enzyme-linked immunosorbent assay (ELISA) against cyst or trophozoite antigens. These 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.

Stool culture
Not useful for diagnosing giardiasis because the organism cannot be grown from patient samples

Serum antibody detection
ELISA assays for serum antibodies against Giardia are not readily available.
It is difficult to make a diagnosis of acute giardiasis because immunoglobulin G (IgG) levels remain elevated for long periods.
However, serum anti-Giardia immunoglobulin M (IgM) can be helpful in distinguishing between acute and past infections.

String test
String test (entero-test) involves a gelatin capsule connected to a weighted nylon string.
The patient tapes one end of the string to his cheek and then swallows the capsule.
After the gelatin is dissolved in the stomach, the weight carries the string into the duodenum.
The string is left there for 4–6 hours or overnight while the patient fasts.
After removal, the string is examined for bilious staining, which identifies successful passage into the duodenum.
The mucus from the string is examined for trophozoites in iodine or saline.

[12]"Diagnostic Tests" section source

Giardiasis
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Agent and taxonomy The disease causing agent of giardiasis is the enteric protozoan parasite Giardia Lamblia. Cross referencing and synonyms: G. intestinalis, G. duodenalis, Giardiasis, Giardia enteritis, Lambliasis, lamblia intestinalis, "beaver fever"[2] Taxonomy and classification of G. lamblia Kingdom: Protista Subkingdom: Protozoa Phylum: Sarcomastia Subphylum: Mastigophora Class: Zommastigophora Order: Diplomonadida Family: Hexamitidae Genus: Giardia Species: lamblia[3] The phylogeny of Giardia is unclear. Because the organisms have simple intracellular structures, they might represent an early branching of eukaryotic lineage that diverges before the acquisition of mitochondria. Elucidating the taxonomy of giardia would significantly aid the understanding of eukaryotic evolution[4] In addition to G. lamblia, which is the only species found in humans,[5] other species of giardia have been identified. Distinction of giardia on the species level is controversial and difficult because of limited knowledge. Based on morphological difference, six species are named: G. lamblia (affects a wide range of mammals such as humans and livestock), G. agilis (affects amphibians), G. muris (affects rodents), G. ardeae and G. psittaci (affect birds), and G. microti (affects muskrats and voles). However, forty-one species can be named if species classification is based on host origins.[6] Recently, advances in molecular biology tools such as PCR have helped elucidate the genetic relationships among morphological identical "strains" of Giardia.[5] Giardiasis Symptoms A range of clinical syndromes may occur, with gastrointestinal syndromes being the most prevalent. [edit] Gastrointestinal A small number of infected individuals experience an abrupt onset of abdominal cramps, explosive, watery diarrhea, vomiting, foul flatus, and fever which may last for 3–4 days before proceeding into a more sub-acute phase. The majority of infected persons develop gradual symptoms that become recurrent or resistant.[12] In both the acute and insidious onsets of symptoms, stools become greasy and malodorous but do not contain blood or pus because giardiasis does not involve dysenteric symptoms. Watery diarrhea may cycle with soft stools and constipation. Upper GI symptoms including nausea, early satiety, bloating, substernal burning, egg-smelling halitosis, and acid indigestion may be exacerbated by eating and are generally present in the absence of soft stools.[12] Physical Abdominal examination may expose nonspecific tenderness even if there is no sign of peritoneal irritation. Rectal examination should expose heme-negative stools and in severe cases, there may be evidence of dehydration.[12] Giardiasis Diagnosis Giardiasis is typically diagnosed by stool ova and parasites (commonly called O&P).[19] It may be found on duodenal biopsies and is in the differential diagnosis of celiac disease. Giardiasis Treatment First line of treatment: Metronidazole (Flagyl) Adult dosage: 250 mg three times a day for 5 days[20] Pediatric dosage: 15 mg per kilogram of body weight per dose, 3 times per day, for 5 days[20] Side effects: Found in 7.1% of cases.[21] Include unpleasant metallic taste which might cause noncompliance in patients, GI discomfort such as vomiting, nausea, diarrhea, abdominal cramps, pancreatitis, vertigo, headache, CNS toxicity, transient leukemia, dizziness, drowsiness, lassitude, paraethesias, urticaria, and pruritis.[21] It causes mutation in salmonella and induces tumor in rodents,[21] but mutagenicity has never been observed in humans.[22] Contraindication: Avoid alcohol while taking metronidazole. Metronidazole causes severe vomiting, headache, and GI discomfort by inhibiting aldehyde dehydrogenase, which breaks down alcohol.[22] Additional drug facts: Metronidazole is a member of the family of nitroimidazoles, commercially known as Flagyl.[21] The tablets are quickly and completely absorbed by the small intestine[22] and found to have antigiardial effects on the trophozoites both in vivo and in vitro.[21] However, it is ineffective against cysts.[21] The drug is able to penetrate body tissues and could be found in saliva, breast milk, semen, and vaginal fluid.[22] It is metabolized in liver and secreted in urine.[22] Metronidazole targets trophozoites by forming active metabolites, which selectively inhibit DNA segregation in anaerobic protozoa such as giardia by DNA breakage and cross-linking.[21] It has minimal effects on host cells lining the intestinal lumen. Resistance is induced in laboratory and is correlated with decreased activity of parasite pyruvate.[22][23] Tinidazole (Fasigyn) Adult dosage: 2 g once[20] Pediatric dosage: 50 mg per kilogram of body weight once (max. 2 g)[20] Side effects: Side effects similar to metronidazole[21] but appears to be better tolerated and just as effective.[20] Common side effects include bitter taste, vertigo, and GI discomfort.[22] The drug should be taken with food to minimize side effects.[20] Additional drug facts: Tinidazole was FDA approved. It is another member of the nitro-imidazole family. Health care providers recommend travelers (especially those traveling to Asian countries) buy the drug at the country of their destination and take it in an event of giardia infection.[22] The drug tablets can also be crushed and mixed with cherry syrup (Humco and others) for children. The syrup suspension can be kept at room temperature for 7 days and should be shaken before use.[20] Nitazoxanide Adult dosage: 500 mg two times a day for 3 days Pediatric dosage: 1–3 yrs: 100 mg every 12 hours for 3 days[20]; 4–11 yrs: 200 mg every 12 hours for 3 days[20] Side effects: A variety of side effects were reported but they occurred infrequently in all studies.[24] Studies failed to provide sufficiently similar results for a comprehensive analysis of the side effects of nitaxonzanide.[24] Some probable adverse effects include abdominal pain, dyspepsia, constipation, yellow discoloration of urine, dysuria and dry mouth, and dizziness.[24] The drug should be taken with food to minimize adverse effects.[20] Additional drug facts: Nitazonxanide is FDA-approved as an oral suspension for treatment of giardiasis. It can be purchased in 500 mg tablets and in oral suspension.[20] Alternative treatment Paramomycin (Humatin) Adult dosage: 25–35 mg per kilogram of body weight per dose, 3 doses per day for 7 days[20] Pediatric dosage: 25–35 mg per kilogram of body weight per dose, 3 doses per day for 7 days[20] Side effects: ototoxicity and nephrotoxicity with systemic administration[22] Contraindication: Patients with impaired kidney function should use paramomycin with caution[22] Additional drug facts: Paramomycin is a member of the aminoglycoside family.[21] It inhibits giardia protein synthesis by targeting the 50S and 30S ribosomal subunits.[22] Its activity in vitro is lower than nitroimidazoles; however, because it is poorly absorbed by small intestine, a higher concentration of the drug remains in the lumen to combat giadia organisms.[22] It is also the choice of drug to treat G. lamblia in resistant infection and during pregnancy.[22] Furazolidone (Furoxone) Adult dosage: 100 mg four times a day for 7–10 days[20] Pediatric dosage: 6 mg per kilogram of body weight per dose, 4 doses per day for 7–10 days[20] Side effects: Gastrointestinal symptoms (nausea, vomiting, diarrhea) are observed in 10% of patients. Other side effects include brown discoloration of urine, and hemolysis in G6PDH-deficient patients.[22] Additional drug facts: it is a member of the nitrofuran family[21] penetrate body tissues and could be found in saliva, breast milk, semen and vaginal fluid.[22] Not recommended to treating pregnant patients because it has been shown to cause mammary tumor in rats and mutations in bacteria.[22] Quinacrine Adult dosage: 100 mg three times a day for 5 days[20] Pediatric dosage: 2 mg per kilogram of body weight, three times per day for 5 days (max. 300 mg/d)[20] Side effects: bitter taste and vomiting observed in 28% of study participants; yellow/orange discoloration of the skin, sclerae, and urine. Other common side effects include nausea, vomiting, headache, dizziness and fever. Drug induced psychosis has been observed but is very rare. Dermatitis and drug-induced retinopathy are also uncommon.[22] The drug also acts with lower efficacy in children because the drug has bitter taste and children are less compliant.[22] Contraindication: Pregnant patients should avoid taking the drug because quinacrine can cross placenta and it might cause spina bifida and renal agenesis in the infant.[22] The drug, unlike metronidazole, also target cysts. This drug cannot be obtained commercially.[citation needed] Albendazole (Albenza) Adult dosage: 400 mg once a day for 5 days[22] Pediatric dosage: 15 mg per kilogram of body weight per day for 5 to 7 days (max. 400 mg)[22] Mebendazole (Vermox) Adult dosage: 200–400 mg per day for 5 to 10 days[22] Side effects for Albendazole and Mebendazole: common side effects include anorexia and constipation. Rare side effects include reversible neutropenia and elevated liver function tests. Whether they are terotogenic is unclear[22] Contraindication of Albendazole and Mebendazole: Albendazole should be taken with caution for pregnant patients because there is a possibility that it might induce tumors. However, animal studies did not reveal increased incidences of cancer.[22] Additional drug facts: Albendazole and Mebendazole are members of the benzimidazole family. They target G. lamblia by binding to β-tubulin and stopping cytoskeletal formation. It also interferes with glucose uptake of the organism.[22] Lab diagnosis Stool examination 3 stools taken at 2-day intervals are examined for ova and parasites. The cysts are detected 50–70% of the time in the first stool specimen examined, and 90% of the time the cysts are detected after 3 stool specimen examinations.[12] Trophozoites disintegrate rapidly outside of the body but may be found in fresh, watery stools. Cysts are found in soft and (semi)formed stools. Cyst passage is variable and not related to clinical symptoms. If not fresh, stool should be preserved in polyvinyl, alcohol, or a formalin. Cyst passage may fall behind the onset of symptoms by a week+ Trichrome stain is useful for finding the cysts and trophozoites. Cysts are smooth walled and oval, measuring 8–12 μm long and 7–10 μm wide. Iodine stains the cysts brown and accentuates their intracystic structures, especially their curved median bodies, axonemes, and nuclei. (4 nuclei representing 2 daughter trophozoites). Trophozoites are leaf-shaped, measuring 9–21 μm long and 5–15 μm wide. Stained organisms have a characteristic facelike image with 2 nuclei Stool antigen detection Commercially available tests use either an immunofluorescent antibody (IFA) assay or a capture enzyme-linked immunosorbent assay (ELISA) against cyst or trophozoite antigens. These 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. Stool culture Not useful for diagnosing giardiasis because the organism cannot be grown from patient samples Serum antibody detection ELISA assays for serum antibodies against Giardia are not readily available. It is difficult to make a diagnosis of acute giardiasis because immunoglobulin G (IgG) levels remain elevated for long periods. However, serum anti-Giardia immunoglobulin M (IgM) can be helpful in distinguishing between acute and past infections. String test String test (entero-test) involves a gelatin capsule connected to a weighted nylon string. The patient tapes one end of the string to his cheek and then swallows the capsule. After the gelatin is dissolved in the stomach, the weight carries the string into the duodenum. The string is left there for 4–6 hours or overnight while the patient fasts. After removal, the string is examined for bilious staining, which identifies successful passage into the duodenum. The mucus from the string is examined for trophozoites in iodine or saline. [12]"Diagnostic Tests" section source
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