General Characteristics

G. lamblia is the most common cause of intestinal infection worldwide. Other than B. hominis, G. lamblia (also called G. duodenalis and G. intestinalis) is probably the most common protozoan organism identified in individuals in the United States. It causes symptoms ranging from mild diarrhea, flatulence, and vague abdominal pains to acute, severe diarrhea to steatorrhea and a typical malabsorption syndrome. Various documented waterborne and food-borne outbreaks have occurred during the past several years. A number of animals may serve as reservoir hosts for G. lamblia. Differentiation of flagellates is based on overall shape, numbers, and arrangements of flagella.

Both the trophozoite and cyst stages are included in the life cycle of G. lamblia. Trophozoites divide by means of longitudinal binary fission, producing two daughter trophozoites. The organism is found most commonly in the crypts in the duodenum. Trophozoites are the intestinal dwelling stage and attach to the epithelium of the host villi by means of the ventral disk. The attachment is substantial and results in disk “impression prints” when the organism detaches from the surface of the epithelium. Trophozoites may remain attached to or may detach from the mucosal surface. Because the epithelial surface sloughs off the tip of the villus every 72 hours, the trophozoites apparently detach at that time. G. lamblia trophozoites are teardrop shaped and have been described as “someone looking at you” (see Figures 1 to 3).

Fig1. 1, Trophozoite of Pentatrichomonas hominis. 2, Trophozoite of Chilomastix mesnili. 3, Cyst of C. mesnili. 4, Trophozoite of  Giardia lamblia (front view). 5, Trophozoite of G. lamblia (side view). 6, Cyst of G. lamblia. 7, Trophozoite of Enteromonas hominis. 8 to 10,  Cysts of E. hominis. 11, Trophozoite of Retortamonas intestinalis. 12 to 13, Cysts of R. intestinalis. (From Garcia LS, Bruckner DA: Diagnostic medical parasitology, Washington, DC, 1993, ASM Press; illustration 5 by Nobuko Kitamura; illustrations 7 to 13 modified from Markell EK,  Voge M: Medical parasitology, ed 5, Philadelphia, 1981, WB Saunders.)

Fig2. A to C, Trophozoites of Giardia lamblia. D to F, Cysts of G. lamblia.

Fig3. A, Giardia lamblia trophozoite. B, G. lamblia trophozoite, iodine stain. C, G. lamblia cysts. (B courtesy Dr. Henry Travers, Sioux  Falls, S.D.) 

Cyst formation takes place as the organisms move down through the jejunum after exposure to biliary secretions. The trophozoites retract the flagella into the axonemes, the cytoplasm becomes condensed, and the cyst wall is secreted (see Figures 1 to 3). As the cyst matures, the internal structures are doubled, so that when excystation occurs, the cytoplasm divides, producing two trophozoites. Excystation occurs in the duodenum or appropriate culture medium.

Epidemiology

 Transmission of G. lamblia occurs by ingestion of viable cysts. Although contaminated food or drink may be the source, intimate contact with an infected individual may also result in transmission of the organism. This organ ism is found more frequently in children or in groups living in close quarters. Outbreaks have been associated with poor sanitation facilities or sanitation breakdowns, as evidenced by infections of travelers and campers. Limited information is available on seasonal variations in giardiasis. Some data suggest an association with the cooler, wetter months of the year, which may implicate environmental conditions as advantageous to cyst survival. Certain occupations may place an individual at risk for infection, such as sewage and irrigation workers, who may be exposed to infective cysts. In situations in which young children are grouped together, such as in nursery schools, an increased incidence of exposure and subsequent infection of both children and staff members may be seen. A high incidence of giardiasis occurs in patients with immunodeficiency syndromes, particularly in those with common variable hypogammaglobulinemia. Giardiasis is the most common cause of diarrhea in these patients and may be associated with mild to severe villus atrophy.

An estimated 200 million people in Asia, Africa, and Latin America have symptomatic infections. In the United States, approximately 20,000 cases are reported yearly. However, an estimated 2 million cases may occur annually.

Pathogenesis and Spectrum of Disease

The incubation period for giardiasis ranges from approximately 12 to 20 days. Giardiasis may not be recognized as the cause, because the infection mimics acute viral enteritis, bacillary dysentery, bacterial or other food poisonings, acute intestinal amebiasis, or “traveler’s diarrhea” (toxigenic Escherichia coli). However, the type of diarrhea plus the lack of blood, mucus, and cellular exudate is consistent with giardiasis.

Asymptomatic Infection. Although the parasites in the crypts of the duodenal mucosa may reach very high numbers, they may not cause a pathologic condition. The organisms feed on the mucous secretions and do not penetrate the mucosa. Although organisms have been seen in biopsy material obtained from inside the intestinal mucosa, others have been seen attached to the epithelium.

Intestinal Disease. For unknown reasons, symptomatic patients may have irritation of the mucosal lining, increased mucus secretion, and dehydration. The onset may be accompanied by nausea, anorexia, malaise, low grade fever, and chills, in addition to a sudden onset of explosive, watery, foul-smelling diarrhea. Other symptoms include epigastric pain, flatulence, and diarrhea with increased amounts of fat and mucus in the stool but no blood. Weight loss often accompanies these symptoms. Although some speculate that the organisms coating the mucosal lining may act to prevent fat absorption, this does not completely explain the prevention of the uptake of other substances normally absorbed at other intestinal levels. Severe malabsorption has also been linked with isolated levothyroxine malabsorption, leading to severe hypothyroidism and secondary impairment of pancreatic function. In both cases, treatment with metronidazole led to complete remission of symptoms. Occasionally the gallbladder is involved, resulting in gallbladder colic and jaundice. G. lamblia also has been identified in bronchoalveolar lavage fluid.

Chronic Disease. The acute phase often is followed by a subacute or chronic phase. Symptoms include recurrent, brief episodes of loose, foul-smelling stools and possibly increased distention and foul flatus. Between episodes of mushy stools, the patient may have normal stools or may be constipated. Abdominal discomfort includes marked distention and belching with a rotten-egg taste. Chronic disease must be differentiated from amebiasis; disease caused by other intestinal parasites (e.g., D. fragilis, Cryptosporidium spp., Cyclospora cayetanensis, Isospora belli, Strongyloides stercoralis); inflammatory bowel disease; and irritable colon. On the basis of symptoms such as upper intestinal discomfort, heartburn, and belching, giardiasis must also be differentiated from duodenal ulcer, hiatal hernia, and gallbladder and pancreatic disease.

Antigenic Variation. Variation of the surface antigen during human infections with G. lamblia has been documented. This capability suggests that variation may provide a mechanism for the organism to escape the host’s immune response. The variant-specific surface proteins (VSPs) are a family of related, highly unusual proteins covering the surface of the organism. VSPs are resistant to the effects of intestinal proteases, which allows the parasites to survive in the protease-rich small intestine. Antigenic variation at the surface membrane of trophozoites occurs frequently; seemingly, the higher the rate of change, the more likely it is that a chronic infection would persist.

Laboratory Diagnosis

 Routine Methods. Routine stool examinations are normally recommended for the recovery and identification of intestinal protozoa. However, in the case of G. lamblia, because the organisms are attached securely to the mucosa by means of the sucking disk, a series of five or six stool samples may be examined without recovering the organism. The organisms also tend to be passed in the stool on a cyclic basis. The Entero-Test capsule can be helpful for recovering the organisms, as can the duodenal aspirate. Although cysts often can be identified on the wet stool preparation, many infections may be missed without examination of a permanent stained smear. If material from the string test (Entero Test, HDC Corp., San Jose, CA) or mucus from a duodenal aspirate is submitted, it should be examined as a wet preparation for motility; however, motility may be represented by nothing more than a slight flutter of the flagella, because the organism is caught up in the mucus. After diagnosis, the positive specimen can be preserved as a permanent stain.

Antigen Detection. The development of fecal immunoassays to detect Giardia antigen in stool has dramatically improved the sensitivity seen with the routine O&P examination. The ELISA has been used to detect Giardia antigen in feces. Fluorescent methods with monoclonal antibodies have also proven extremely sensitive and specific in detecting G. lamblia in fecal specimens. Other products are available as a cartridge format that uses an immunochromatographic strip–based detection system for G. lamblia and/or Cryptosporidium spp. Any antigen detection system should always be reviewed for compatibility with stools submitted in preservatives rather than fresh specimens. Some limitations exist on the use of kits for organisms in the genus Entamoeba. However, commercial reagent kits for detecting Giardia and Cryptosporidium spp. can be used with formalin-based stool preservatives or with fresh or frozen specimens. Many of these cartridge format tests provide an answer within 10 minutes and are equal to or better than other immunoassays with regard to sensitivity and specificity. Many of these newer methods are being used to test patients suspected of having giardiasis or those who may be involved in an outbreak.

The detection of antigen in stool or visual identification of organisms by using monoclonal antibody reagents indicates current infection. The value of these detection assays as rapid, reliable immunodiagnostic procedures has been emphasized by the increase in Giardia infections and the greater awareness of particular incidences (e.g., nursery school settings). Because the organisms are shed so sporadically, use of a fecal immunoassay does not eliminate the need to analyze multiple stool specimens for sensitive detection of G. lamblia; a minimum of two stools should be tested. If the first specimen is negative, it may represent a false negative.

Antibody Detection. Unfortunately, serodiagnostic procedures for antibody detection do not fulfill the criteria necessary for wide clinical use, particularly because they may indicate either past or present infection.

Histology. Trophozoites are detectable in the duodenum and proximal jejunum; however, mucosal invasion generally has been found in areas where necrosis or mechanical trauma was present. Changes range from normal to almost complete villus atrophy, with a greater density of inflammatory infiltrate in the lamina propria when villus atrophy is present. The amount of villus damage seems to correlate with the degree of malabsorption. Apparently, patients with giardiasis also have reduced mucosal surface areas compared with control patients.

Histologic changes in the mucosal architecture in immunodeficient patients with giardiasis also range from mild to severe villus atrophy. It appears that giardiasis produces a more severe degree of villus damage in patients with hypogammaglobulinemia. In patients with acquired immunodeficiency syndrome (AIDS), giardiasis does not appear to be an important pathogen, although the infection has certainly been found in this group and in homosexual men.

Nucleic Acid-Based Techniques

 Currently, there are no molecular-based assays commercially available for the detection of G. lamblia.

Prevention

The most effective practice for preventing the spread of infection in the child care setting is thorough hand washing by the children, staff members, and visitors. Rubbing the hands together under running water is the most important part of washing away infectious organ isms. Premoistened towelettes or wipes and waterless hand cleaners should not be used as substitutes for washing the hands with soap and running water. These guidelines are not limited to giardiasis but include all potentially infectious organisms.

Because wild animals and possibly domestic animals serve as reservoir hosts, personal hygiene, improved sanitary measures, and safe drinking water are considerations. Iodine has been recommended as an effective disinfectant for drinking water. Filtration systems have also been recommended, although they have certain drawbacks, such as clogging.

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