Download Giardiasis

1
Giardiasis
William A. Petri, Jr., M.D., Ph.D.
William A. Petri, Jr., M.D., Ph.D.
Professor of Medicine, Microbiology, and Pathology
Chief, Division of Infectious Diseases & International Health
University of Virginia
Charlottesville VA 22908
[email protected]; 434/924-5621 (tel); 434/924-0075 (fax)
Introduction
Giardiasis is an important parasitic cause of diarrheal disease. It is the most
common parasite identified in stool samples of individuals in the United States, present in
about 4% of stool specimens submitted to clinical laboratories1 . The disease is quite
common in developing countries, especially in urban slums where a substantial number of
children are infected. Water and food borne transmission are the most frequent
mechanisms of spread, with person to person spread important in day care settings and
among sexually active homosexual males.
In the military, giardiasis will most often be encountered during or after return
from deployment to developing countries. An example of the increased risk for giardiasis
in developing countries is the experience with diarrheal illness in expatriate residents and
tourists to Nepal, where 9-16% had Giardia lamblia identified in their stools2. In
Operation Restore Hope in Somalia from 1992-1993, 0.8% of personnel sought care for
diarrheal illness each week and < 3% of all personnel reported a diarrheal illness per
week. Giardia lamblia was isolated from 4% of personnel with diarrhea, making it the
third most common enteropathogen identified (Shigella sp. were isolated from 33% and
enterotoxigenic E. coli from 16%). The relatively low overall attack rate of diarrhea
(compared to previous deployments in developing countries) likely was due to the lack of
consumption of local food products due to the economic devastation and security threats
within Somalia. As in previous deployments personnel drank bottled water from
approved vendors and pre-prepared food from the United States3. A survey of 422
Marines returned from Operation Desert Storm similarly revealed a 2% incidence of
Giardia lamblia cysts. The risk of contracting giardiasis is not only in developing
countries however. In a Utah Army National Guard field training exercise in the Rocky
Mountains of the United States, 15% of all personnel reported symptoms consistent with
giardiasis, and symptoms were reported in 62% of personnel who supplemented their
water supply with raw water from lakes, streams and a cattle watering trough4!
Description of the Organism
2
Giardia lamblia has also been called G. intestinalis and G. duodenalis. The
infective form of the parasite is the cyst, which is 7-10 µm wide and 8-12 µm long with a
refractile cell wall and contains 2-4 nuclei. Trophozoites contain 2 nuclei and 4 flagella
and are 12-15 µm long by 5-10 µm wide. The nuclei have a characteristic central
karyosome which gives the trophozoite its face-like appearance in stained specimens.
The dorsal surface of the trophozoite is round and smooth, while the ventral surface has a
concave anterior disc that is thought to function in adhesion to the intestinal epithelium.
Epidemiology
The 3 most common intestinal parasites identified as causes of diarrhea in the
United States are Giardia lamblia (9.5 cases per 100,000 population), Cryptosporidium
parvum (1.4 cases/100,000 population), and Entamoeba histolytica (1.2 cases/100,000
population).
Giardiasis is highly infectious - ingestion of as few as 10-25 cysts produces
disease in human volunteers. Giardiasis occurs in all parts of the world and is a common
cause of water borne outbreaks of diarrhea in the United States. In some urban slums in
developing countries rates of giardia infection approach 100% 5 . Even seemingly pristine
mountain streams in North America can be contaminated with giardia, with the infectious
giardia cysts extremely stable in cool water.
Water borne transmission is an important route of acquisition of giardiasis.
Consumption of improperly treated surface water (as opposed to well water) is the most
important risk factor. Water borne outbreaks have occurred in the Rocky Mountain areas
of the United States and Canada, and the Northwestern and Northeastern United States.
Proper filtration of surface water supplies is the most important factor in prevention of
these outbreaks, as the cysts of giardia are not completely inactivated by the flocculation,
sedimentation and chlorination steps of water purification. Hikers and campers who
consume untreated stream or other surface water are at risk for infection with giardia.
Surface water may be contaminated not only with giardia from human sources, but also
with giardia from beavers, muskrats and possibly other animals which have the potential
to transmit giardia to humans6 .
Person to person spread of giardia infection is documented in children and
employees in day care centers, in sexually active male homosexuals, and in residents of
institutions for the mentally handicapped. Surveys of children under age 3 in day care
centers have measured giardia infection rates as high as 25-50%7 . Most of these
infections are asymptomatic: studies demonstrated that children with giardia infection had
normal nutritional status and were not more likely to have enteric symptoms. Parents of
children in day care, and day care workers, have a higher rate of giardia infection than the
overall population. Homosexual men seen in sexually transmitted disease clinics have
rates of giardia infection as high as 10%.
Food borne transmission has more recently been appreciated to occur with giardia.
In one instance 32 employees of a public school system developed symptomatic giardiasis
after eating home-canned salmon. The salmon had been prepared by a grandmother who
had just diapered her grandson, and the grandson was subsequently shown to have giardia
infection8 . Outbreak investigations need to consider the possibility of food borne
transmission, although water borne is more common.
3
Pathogenesis
Infection is initiated by the oral ingestion of G. lamblia cysts. Excystation follows
ingestion, with the trophozoites multiplying in the small bowel. The infection remains
luminal in almost all cases, with rare exceptions of mucosal invasion by the trophozoites.
The parasite may adhere to the intestinal epithelium via its ventral disk or via a parasite
carbohydrate-binding adhesin protein. Trophozoites encyst in the bowel lumen, with an
encystation-specific secretory vesicle system implicated in synthesis of the cyst wall9 .
The pathogenesis of diarrhea is not clear. No enterotoxin has been characterized,
and the organism is normally not invasive. Damage to intestinal epithelial cells and
atrophy of microvilli have been shown in biopsies of some patients with giardiasis.
Malabsorption of protein, D-xylose and fat soluble vitamins as well as disaccharidase
deficiency occurs in some patients with giardiasis.
Different strains of the parasite differ in their ability to cause infection and
diarrhea in human challenge studies. Parasite surface antigen variation has been
documented in vitro and in experimental human infections, and the antibody response has
been shown to be isolate specific, suggesting that antigenic variation may be a mechanism
of immune evasion1 0 .
Evidence for acquired immunity to giardiasis includes the lower incidence of
infection in adults than in children, and the observation from epidemiologic and human
experimental challenge studies that symptomatic infections with giardia are more
common with the first episode of infection than with later infections5 , 1 0 .
Clinical Findings
Infection can be manifest after return from an endemic or high risk area, as the
average incubation period from infection to onset of diarrhea is 7 days, and can be as late
as 28 days. The typical patient with symptomatic giardiasis will have an illness lasting 7
days or more with some combination of symptoms including diarrhea, flatulence, foulsmelling stools, nausea, abdominal cramps and excessive tiredness. The most notable
feature of the illness is the prolonged nature of the diarrhea and the malabsorption that
may be present1 1 . Lactase deficiency and malabsorption of D-xylose, protein, fat and fat
soluble vitamins may all occur to varying degrees. Stool specimens are semi-formed or
loose, lack occult blood, but may contain mucus and/or fecal leukocytes. Especially in
endemic settings such as day care centers in the developed world and urban slums in
developing countries, most giardia infection is asymptomatic. Protection against
symptomatic infection in children under 18 months of age has been associated with breast
feeding.
Diagnostic Approaches and Differential Diagnosis
4
Consider the diagnosis of giardiasis in outbreaks or individual cases of diarrheal
illnesses of 5-7 days or more duration. Travel to a developing country, exposure to
children in day care or to institutionalized individuals, and active male homosexual
practices should all increase the suspicion of giardiasis. Common source outbreaks can
be either water- or food-borne.
Historically giardiasis has been diagnosed by identification of the trophozoite
and/or cyst in stool specimens. The motile trophozoite can sometimes be identified in
saline wet mount of fresh stool. Cysts can be stained with iodine or in polyvinyl alcohol
preserved stools with trichrome or iron hematoxylin stains. Because of the difficulties in
morphologic identification of the parasite, most laboratories are now detecting the
infection using antigen detection assays. Antigen detection assays are now available in
immunofluorescent and enzyme immunoassay formats (TechLab, Meridian Diagnostics,
Alexon, Trend Scientific, Cambridge Biotech, and Seradyn all market antigen detection
tests for giardia). These tests have comparable, and in many cases improved sensitivity
and specificity, compared to microscopy. Sampling of duodenal contents for giardia by
aspiration, biopsy, or string test is almost never necessary if careful examination of stool
with antigen detection tests or stool microscopy is performed.
Recommendations for Therapy and Control
Metronidazole or tinidazole are the drugs of first choice for treatment of
giardiasis, although they do not have a Food and Drug Administration indication for this
use; tinidazole has recently become available in the U.S. Tinidazole (2 grams once in
adults) or metronidazole (250 mg tid for adults x 7 days) are 80-95% effective. Side
effects of treatment include a disulfiram-like reaction when taken with alcohol, as well as
nausea, dry mouth and headache. Dizziness, vertigo, paresthesias, and rarely
encephalopathy or convulsions can be neurologic side effects and warrant discontinuation
of the drug. A temporary neutropenia has been associated with metronidazole, and is
reversible upon discontinuation of the drug. There is no evidence of carcinogenicity or
mutagenicity of metronidazole in humans, although use during the first trimester is not
indicated. Alternative drugs include furazolidone (100 mg QID x 7-10 D in adults),
which can cause hemolysis in individuals with glucose -6-phosphate dehydrogenase
deficiency, quinacrine (100 mg tid x 5D in adults) which is poorly tolerated because of
nausea, vomiting and cramping and is currently unavailable in the U.S., and
paromomycin (25-35 mg/kg/D in 3 doses x 7D in adults) for which clinical experience in
the treatment of giardiasis is limited1 2 . In patients with a history of exposure and clinical
findings consistent with giardiasis, but with negative stool diagnostic studies for G.
lamblia and other enteropathogens, many authorities recommend empiric treatment
because of the difficulties in sensitivity of diagnostic tests.
Prevention of water borne outbreaks requires proper flocculation, sedimentation,
filtration, and chlorination of water supplies. Filtration is the single most important step
for removal of the chlorine-resistant giardia cysts from community water supplies. Good
personal hygiene is required to prevent transmission by food handlers and in day care
centers. For military personnel in the field, all surface water should be considered to be
contaminated with giardia. Approaches to field water purification include bringing the
water to a boil for 1 min, filtration through a 2 µm filter, or treatment for 30 min with
halazone (5 tablets/liter for 30 min), Globaline (tetraglycine hydroperiodide, 1 tablet per
5
quart), or saturated crystalline iodine (12.5 ml/liter for 30 min). Halazone or iodine
treatment of water is less effective at 3° C than at 20° C1 0 .
References
1. Hill DR. Giardia lamblia. In Principles and Practice of Infectious Diseases 4th
Edition (Mandell GL, Bennett JE, Dolin R eds) Churchill Livingstone, N.Y., 1995: 248792.
2. Hoge CW, Shlim DR, Echeverria P et al. Epidemiology of diarrhea among expatriate
residents living in a highly endemic environment. JAMA 1996; 275:533-8.
3. Sharp TW, Thornton SA, Wallace MR et al. Diarrheal disease among military
personnel during operation Restore Hope, Somalia, 1992-3. Am. J. Trop. Med. Hyg.
1995; 52:188-93.
4. Laxer MA. Potential exposure of Utah Army National Guard personnel to giardiasis
durig field training exercises: a preliminary survey. Military Med 1985; 150:23-26.
5. Oyerinde PO, Ogunbi O, Alonge AA. Age and sex distribution of infections with
Entamoeba histolytica and Giardia intestinalis in the Lagos population. International J
Epidemiology. 1977; 6:231-4.
6. Erlandsen SL, Sherlock LA, Januschka M, Schupp DG, Schaeffer FW III, Jakubowski
W, Bemrick WJ. Cross-species transmission of Giardia spp.: Inoculation of beavers and
muskrats with cysts of human, beaver, mouse and muskrat origin. Applied
Environmental Microbiol. 1988; 54:2777-85.
7. Pickering LK, Woodward WE, DuPont HL, Sullivan P. Occurrence of Giardia
lamblia in children in day care centers. J Pediatrics. 1984; 104:522-6.
8. Osterholm MT, Forfang JC, Ristinen TL, Dean AG, WAshburn JW, Godes JR, Rude
RA, McCullough JG. An outbreak of foodborne giardiasis. New Engl J Med. 1987;
304:24-27,
9. Reiner DS, McCaffery M, Gillin FD. Sorting of cyst wall proteins to a regulated
secretory pathway during differentiation of the primitive eukaryote, Giardia lamblia.
European J Cell Biology. 1990; 53:142-153.
10. Nash TE, Herrington DA, Levine MM, Conrad JT, Merritt JW Jr. Antigenic variation
of Giardia lamblia in experimental human infections. J Immunol. 1990; 144:4362-9.
11. Hopkins RS, Juranek DD. Acute giardiasis: an improved clinical case definition for
epidemiologic studies. American J Epidemiol. 1991; 133:402-7.
12. Tracy JW, Webster LT. Drugs used in the chemotherapy of protozoal infections:
Trypanosomiasis, leishmaniasis, amebiasis, giardiasis, trichomoniasis, and other
6
protozoal infections. In Goodman & Gilman’s The Pharmacological Basis of
Therapeutics, 9th Edition (Hardman JG, Limbird LE eds), McGraw Hill, NY, 1996: 9871008.
13. Kahn FH, Visscher BR. Water disinfection in the wilderness. West J Med. 1975;
122:450-453.
Table: Symptoms and Signs of Giardiasis11
Prolonged diarrhea
Fatigue
100%
97%
Abdominal cramps
83%
Bloating
79%
Malodorous stool
79%
Flatulence
76%
Weight loss
59%
Fever
21%
Vomiting
17%