Friday, December 4, 2015

GIARDIA: From Structure to Disease

by ET

Giardia lamblia is a flagellate protozoan, an intestinal parasite that commonly causes diarrheal disease throughout the world. The protozoan exhibit pear-shaped cells that are approximately 12-15 um wide. It is the common agent that causes most waterborne outbreaks of diarrhea in the United States, although it’s occasionally seen as a cause of food-borne diarrhea (1).
Infection is initiated through ingestion of Giardia lamblia cysts and numerous different strains may be found in one host during the course of the infection. About 10-25 cysts are capable of causing a disease with minor symptoms, however, ingestion of more than 25 cysts results in a 100% infection rate (3,4).
Giardia lamblia, cyst form   
The cyst morphology of this protozoan organism is smooth-walled, oval in shape and contains four nuclei. The cyst is relatively stable and can survive in a variety of environmental conditions for a prolonged time. In addition, it also survives acidic environments within the stomach and then initiates replication in the small intestine, where it causes symptoms of diarrhea and malabsorption. Upon excitation, a mature cyst releases 2 trophozoites. When the host is infected, thropozoites may appear in the duodenum within a few minutes. The major component of the cyst wall is N-galactosamine, which is produced by the enzymatic pathway that is induced during encystation (1,2).
The anatomical structure of this organism is quite unique. The ventral disk is an important component of Giardia lamblia cytoskeleton and is crucial in the survival of the organism in the intestine of the host. It is used by the organism for sucking, adhesion and holding abilities within the host. Giardia lamblia exhibits concave structure and covers the entire surface of the organism. The disk contains contractile proteins such as actin, myosin, and tropomyosin (2,3).
Also, the presence of the lectins on the surface of the organism ensures the attachment of the Giardia to the enterocyte within the host. Attachment to the host depends on the host’s active metabolism and is inhibited by temperature at 37C, high oxygen levels, and/or reduced cysteine concentrations. It is important to note that Giardia has nucleus and nuclear membrane, cytoskeleton and endomembrane system but it lacks other organelles such as nucleoli and peroxisomes that are nearly universal to eukaryotic organisms. Also Giardia are characterized by their lack of mitochondria and cytochrome mediated oxidative phosphorylation. They rely mostly on fermentation metabolism for energy conservation. Thus, glucose promotes growth of this microorganism but its not absolutely essential (1,2).
The development of good molecular classification tools and better understanding host specificity makes it reasonable to address the possibility of coevolution of different species or genotypes of this organism with their host. Several studies suggest that some genotypes of Giardia lamblia have a wide-ranging host specificity that includes humans while others appear to be more restricted and may not pose a risk of zoonotic transmission (1,2).
The mechanism by which Giardia causes symptoms of diarrhea and malabsorption are not yet fully understood. However, some recent research suggests that the damage of the endothelial brush border and endotoxins alter secretion and gut motility within the stomach. The damage of the endothelial wall occurs when Giardia lamblia releases substances that damage the intestinal epithelium. Also, lectins on the surface of the Giardia may contribute to the epithelial damage (4).
Giardia lamblia life cycle   
The life cycle of the Giardia lamblia is composed of two stages: the thropozite stage that freely exists within the human small intestine and the cyst stage, which is passed into the environment. No intermediate host is required within the life cycle. During the second stage excystation occurs in the stomach and the duodenum in the presence of acid and pancreatic enzymes. The thropozites pass into the bowel where they rapidly multiply within 9-12 hours. As they pass into the large bowel, encystation occurs in the presence of the neutral pH and bile salts. Then cysts are passed into the environment and the cycle is repeated again (1,2).
There are several types of transmission: person-to-person, water-borne and venereal transmission. Person-to-person transmission is mostly associated with poor hygiene and sanitation. Water-borne transmission is commonly associated with the ingestion of an unfiltered water surface. Venereal transmission types occur through fecal-oral contamination.
Giardia affects people of all ages. The infection is rare in newly-born infants, however, children that are older than 6 months have a higher susceptibility rate. High-risk groups for the infection include travelers who visit highly endemic areas, homosexual men and immuno-compromised individuals. Giardiasis is slightly more common in males than females. High incidence rates of the giardiasis are reported in daycare centers, institutions, and Native American Reservations.  The highest prevalence of the infection was documented in Western Nepal, Bangladesh, and Ethiopia.
The prognosis for the infected patients is generally excellent. Most patients are asymptomatic and most developing infections are self-limited. Also weight loss, disaccharide deficiency, and growth retardation are possible complications. This infection is rarely associated with mortality except in rare cases when extreme dehydration in infants or malnourished children occurs. Untreated giardiasis can last for weeks. The parasite persists in stool and re-infection is possible as well. Several antibiotic agents are available with good efficiency rates to shorten the course of the disease. However, drug resistance also has been observed in clinical experiments.
To prevent giardiasis, travellers should be educated regarding proper hygiene methods and symptoms of infection. Careful washing should be emphasized in order to prevent infection. Personal hygiene education to minimize person-to-person transmission in high-risk settings must be introduced.

1.     Daly ER, Roy SJ, Blaney DD, et al. Outbreak of giardiasis associated with a community drinking-water source. Epidemiol Infect. Apr 2010;138(4):491-500.
2.     Adam, R. D. "Biology of Giardia Lamblia." Clinical Microbiology 14.3 (2001): 447-75.
3.     Farthing MJ. Giardiasis. Gastroenterol Clin North Am. Sep 1996;25(3):493-515
4.     Buret AG. Mechanisms of epithelial dysfunction in giardiasis. Gut. Mar 2007;56(3):316-7.

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