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Abstract
Giardia lamblia, Giardia intestinalis or Giardia duodenalis, is a flagellated enteric unicellular eukaryotic microorganism that commonly causes diarrheal disease throughout the world. It was first described in 1681 after the Dutch microscopist Antonie Van Leeuwenhoek who observed the protozoan in one of his own diarrheic stools(1-3).
Giardiasis is considered the most common protozoal infection in humans, it occurs frequently in both developing and industrialized countries. Worldwide prevalence is believed to range between 20-60% , 2-7% in industrialized nations(4-8).
Research into its epidemiology, pathogensis and treatment has intensified since Giardia lamblia waterborne outbreaks were reported in United States during the 1960s to 1970s(9,10).
Despite the recognition of Giardia lamblia illness for the last 40 years(11) and the millions infected worldwide, there has been no definitive treatment protocols published. In addition only a handful of agents had been used in therapy and the agents which are available may have adverse effects or be contraindicated in certain clinical situations. Also resistance may play a role in some infections(12-14).
Epidemiology
Public health interest in Giardia lamblia is increasing because of the growing recognition of its role as a cause of disease outbreaks in a range of settings(15,16). Giardia lamblia is now the most wide spread human intestinal parasite in the world. Approximately 280 million people are infected with the parasite globally, with 500000 new cases reported annually(17).
Giardiasis occurs throughout tropical and temperate regions. In Egypt, a high prevalence of Giardia lamblia infection (35%) was detected in primary school children in Sherbeen city, Dakahlia Governorate(18). Lower rates(22.3%) were reported in primary school children in Mansoura(19), Alexandria (15.4%)(20)and Qualyoub cities (9.5%)(21). On rural Egypt in Belbeis population, the most prevalent diarrhoeic agent in children less than five years old was Giardia lamblia in 4% of cases(22).
Giardia lamblia was reported from many countries. For example, it was observed in 36% of primary school children in Northern Jordan. The infection rates were higher in the younger age group where several of them had diarrhoea and reported variable symptoms. Infection rates declined with age and children were asymptomatic. Rates were higher in children from the rural areas, from low income families, and it was higher in girls than boys(23). In Saudi Arabian children aged less than 14 years, the most prevalent intestinal protozoan was Giardia lamblia 8.9%(24). In Sudan, Giardia lamblia infection was detected in 9.8% of childern of two primary schools in Southern Sudan(25). In Gaza Strip, it was detected in 17.2% of primary school children(26).
2 - 7% In developed countries, Giardia lamblia has the distinction of being the most commonly reported human parasite(27). including North America, Australia, and New Zealand(7). Giardiasis has been a notifiable disease in New Zealand since 1st July 1996 (28) and is the third most commonly notified communicable disease there. The incidence rate in New Zealand in 2002 was 41.40 per 100,000 population and is thought to be one of the highest incidence among developed countries(29).
In South Africa (KwaZulu-Natal), Giardia lamblia was found to be endemic with an incidence about 3% of diarrhoea samples and Giardia lamblia was most prevalent in the 3 - 4 years age group (38.5%).
A low percentage of 5.3% Giardia lamblia positive cases were recorded in symptomatic patients.(30) In Island of Bioko (Equatorial Guinea) the prevalence of Giardia lamblia was associated with presence or absence of diarrhea in 7.2 %.(31)
MORPHOLOGY AND LIFE CYCLE
Giardia lamblia has two forms; the trophozoite and the cyst (infective stage). The life cycle of Giardia lamblia begins by ingesting cyst form in contaminated water or food or directly from fecal-oral contact. Another mode of infection is by infected insect(house fly) or through sexual way among homosexual. As few as 10 cysts may establish infection. After ingestion excystation occurs, which is thought to be initiated by contact with acidic gastric contents, followed by a highly coordinated sequence of events leading to the release of one or two trophozoites. A parasite derived protease may be activated during the excystation process. The trophozoite infects the duodenum and upper intestine, which have a favorable alkaline pH, and gives rise to the clinical sequelae. As trophozoites pass through the small intestine to the colon, encystation occurs. Encystment probably is a periodic phenomenon therefore cysts may not always be detected in stools even if trophozoites are present in the duodenum(32-35).
Trophozoite is easily recognized under a microscope. It is about 10 to 20μm in length and 5 to 15μm in width and shaped like a pear, with broad anterior and attenuated posterior end. The dorsal surface is convex while the ventral surface has an anterior ovoidal concavity(36). Cut in half lengthwise, it is bilaterally symmetrical with each structure being paired. The anterior portion of the ventral surface of the organism is modified to form a sucker disk which serves for attachment. The sucker disk is bordered by the curved intracytoplasmic portion of anterior flagella (the axonemes)(37).
In the middle of the organism it has a pair of axostyles with two parabasal bodies (curved rods) across them that resemble a mouth; the axostyles are the intracytoplasmic portions of the caudal pair of flagella. Two curved rods are seen posterior to the sucker disk, these rods are known as median bodies(38).
Lateral to the axostyles are two spherical nuclei that have prominent central karyosomes with no peripheral chromatin, they resemble eyes. The four pairs of flagella are located at the anterior, lateral caudal and ventral aspects of the trophozoites. The flagella look like hair. All these structures combine to give the stained trophozoites the eerie appearance of a face(39).
The trophozoites of Giardia lamblia are found in upper part of small intestine where they live closely applied to the mucosa, they may be found at times in the gall bladder and in biliary drainage. Giardia lamblia attachment to duodenal mucosa is mainly by sucking disk and may be facilitaed by a lectin production by the parasite and activated by duodenal secretions. Its motility is erratic with slow oscillations along its axis like the motion of falling leaf. The flagella help these organisms to migrate to a given area of small intestine(40).
The cysts are oval and measure 8 to 12μm in length and 7 to 10μm in width. The structure of cysts differs from that of trophozoites by absence of flagella and sucking disks and by their four nuclei. Through binary fission a cyst transforms into two binucleated trophozoites immediately after excystment. By the addition of D´Antony´s iodine it usually reveals the nuclei and the median bodies in the specimens(41).
Molecular classification tools have been of great value in understanding the pathogenesis and host range of Giardia lamblia isolates obtained from humans and a variety of other mammals(42).The first study of the molecular differences of Giardia lamblia isolates, was a zymodeme analysis of five axenized isolates, three from humans, one from guinea pig and one from a cat, using six metabolic enzymes(43).
Zymodeme analysis consists of the typing of organisms based on the migration of a set of enzymes on a starch gel in the presence of an electric filed(44). The migration depends on the size structure and isoelectric point of these enzymes. Since these properties are a function of the primary amino acid sequence, differences in the zymodeme should reflect differences in the sequences of the genes encoding these enzymes(45). Restriction fragment length polymorphism analysis of 15 isolates was performed using random probes(46).
These studies resulted in the description of three groups: group 3 was so different from group 1and group 2 that the suggestion of a separated species designation was made. Subsequently, a number of other molecular classification studies have been performed using zymodeme analysis (47) and restriction fragment length polymorphism analysis.
These studies have all confirmed the division of Giardia lamblia human isolates into two major genotypes(48). The first consists of Nash groups 1and 2, Mayrhofer assemblage A, groups 1 and 2, and the polish isolates(49) while Nash group 3, Mayrhofer assemblage B, groups 3 and 4, and the Belgian isolates form the other major genotype(50).
The two genotypes may have a number of important biologic differences(51). For example, the GS isolate group 3 was significantly more pathogenic in infections of human volunteers than was the WB isolate group 1. Group 3 organisms also appear to grow much more slowly in axenic culture than do genotype 1 organisms(52).
Giardia lamblia isolates from a variety of mammals: these isolates are morphologically identical to human Giardia lamblia but sequences of their protein coding regions differ. The studies have allowed the identification of a dog isolate that is genetically distinct from human Giardia lamblia(53).