The flagellated unicellular parasite Giardia duodenalis (also sometimes known as G. intestinalis or G. lamblia) resides in the intestines of humans and a range of other vertebrates. Giardia lack common eukaryotic subcellular compartments such as mitochondria, peroxisomes, and apparently also a traditional Golgi apparatus. Six Giardia species are currently recognized. Five of these are represented by isolates from amphibians (G. agilis), birds (G. ardeae, G. psittaci), mice (G. muris), and voles (G. microti). Thje sixth species (G. duodenalis, sometimes treated as a species complex rather than a single species) includes Giardia strains isolated from a large range of other mammalian hosts (including humans, domestic dogs, cats, and livestock). Plutzer et al. (2010) reviewed the biology, epidemiology, detection, and control of Giardia. (Plutzer et al. 2010 and references therein; Tangtrongsup and Scorza 2010).
Giardia cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts (the dormant, environmentally resistant stage, which measure around 12 microns long and 7 microns wide) and trophozoites (the active, motile stage, which measure around 15 microns long and 8 microns wide) can be found in the feces. The cysts are hardy and can survive several months in cold water. Infection occurs by the ingestion of cysts in contaminated water or food, or by the fecal-oral route (hands or fomites, i.e., inanimate objects or substances capable of transferring pathogens). In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites). Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel, where they can be either free or attached to the mucosa by a ventral sucking disk. Encystation occurs as the parasites move toward the colon. The cyst is the stage found most commonly in nondiarrheal feces. Because the cysts are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible. Non-human animals are infected with Giardia, but their importance as a reservoir for human infection is unclear. Giardia infects humans worldwide, but is more prevalent in warm climates and in children. (Tangtrongsup and Scorza 2010; Centers for Disease Control Parasites and Health Website)
Giardia cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts and trophozoites (the active stage) can be found in the feces (diagnostic stages). The cysts are hardy and can survive several months in cold water. Infection occurs by the ingestion of cysts in contaminated water or food or by the fecal-oral route (hands or fomites, i.e., inanimate objects or substances capable of transferring pathogens). In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites). Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel, where they can be free or attached to the mucosa by a ventral sucking disk. Encystation occurs as the parasites transit toward the colon.The cyst is the stage found most commonly in nondiarrheal feces. Because the cysts are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible. Non-human animals are infected with Giardia, but their importance as a reservoir for human infection is unclear. Giardia infects humans worldwide, but is more prevalent in warm climates and in children.
Evolution and Systematics
Flagella of Giardia facilitate swimming and attaching by having each of the four pairs of flagella conduct different functions.
"...we discovered that, during rapid swimming of Giardia trophozoites, undulations of the caudal region contributed to forward propulsion combined with the beating of the flagella pairs... the anterior and posterolateral flagella beat with a clearly defined power stroke and not symmetrical undulations. During the transition from free swimming to attachment, trophozoites modified their swimming behavior from a rapid rotating motion to a more stable planar swimming. While using this planar swimming motion, the trophozoites used the flagella for propulsion and directional control...The results from this study indicate that Giardia is able to simultaneously generate both ciliary beating and typical eukaryotic flagellar beating using different pairs of flagella." (Lenaghan et al. 2011:E550)
Learn more about this functional adaptation.
- Lenaghan SC; Davis CA; Henson WR; Zhang Z; Zhang M. 2011. High-speed microscopic imaging of flagella motility and swimming in Giardia lamblia trophozoites. PNAS. 108(34): E550-E558.
Giardia lamblia is a flagellated protozoan parasite that colonizes and reproduces in the small intestine, causing giardiasis. The parasite attaches to the epithelium by a ventral adhesive disc, and reproduces via binary fission. Giardiasis does not spread via the bloodstream, nor does it spread to other parts of the gastrointestinal tract, but remains confined to the lumen of the small intestine. Giardia trophozoites absorb their nutrients from the lumen of the small intestine, and are anaerobes. If the organism is split and stained, its characteristic pattern resembles the familiar "smiley face" symbol. Chief pathways of human infection include ingestion of untreated sewage, a phenomenon particularly common in many developing countries; contamination of natural waters also occurs in watersheds where intensive grazing occurs.
Giardia infection can occur through ingestion of dormant microbial cysts in contaminated water, food, or by the faecal-oral route (through poor hygiene practices). The cyst can survive for weeks to months in cold water, so can be present in contaminated wells and water systems, especially stagnant water sources, such as naturally occurring ponds, storm water storage systems, and even clean-looking mountain streams. They may also occur in city reservoirs and persist after water treatment, as the cysts are resistant to conventional water treatment methods, such as chlorination and ozonolysis. Zoonotic transmission is also possible, so Giardia infection is a concern for people camping in the wilderness or swimming in contaminated streams or lakes, especially the artificial lakes formed by beaver dams (hence the popular name for giardiasis, "beaver fever").
In addition to waterborne sources, fecal-oral transmission can also occur, for example in day-care centers, where children may have poor hygiene practices. Those who work with children are also at risk of being infected, as are family members of infected individuals. Not all Giardia infections are symptomatic, and many people can unknowingly serve as carriers of the parasite.
The life cycle begins with a noninfective cyst being excreted with the faeces of an infected individual. The cyst is hardy, providing protection from various degrees of heat and cold, desiccation, and infection from other organisms. A distinguishing characteristic of the cyst is four nuclei and a retracted cytoplasm. Once ingested by a host, the trophozoite emerges to an active state of feeding and motility. After the feeding stage, the trophozoite undergoes asexual replication through longitudinal binary fission. The resulting trophozoites and cysts then pass through the digestive system in the faeces. While the trophozoites may be found in the faeces, only the cysts are capable of surviving outside of the host.
Distinguishing features of the trophozoites are large karyosomes and lack of peripheral chromatin, giving the two nuclei a halo appearance. Cysts are distinguished by a retracted cytoplasm. This protozoan lacks mitochondria, although the discovery of the presence of mitochodrial remnants (organelles) in one recent study "indicate that Giardia is not primitively amitochondrial and that it has retained a functional organelle derived from the original mitochondrial endosymbiont". This organelle is now termed a mitosome.
Intracellular metabolism and biochemistry
Giardia relies on glucose as its major energy source and breaks glucose down into ethanol, acetate and carbon dioxide. However, it can also use arginine as an energy source. Giardia possesses unique biochemical pathways that suggest it diverged from other eukaryotes at an early stage in evolution.
Manifestation of infection
Nomenclature of Giardia species is difficult, as humans and animals appear to have morphologically identical parasites.
Colonization of the gut results in inflammation and villous atrophy, reducing the gut's absorptive capability. In humans, infection is symptomatic only about 50% of the time, and protocol for treating asymptomatic individuals is controversial. Symptoms of infection include (in order of frequency) diarrhea, malaise, excessive gas (often flatulence or a foul or sulphuric-tasting belch, which has been known to be so nauseating in taste that it can cause the infected person to vomit), steatorrhoea (pale, foul smelling, greasy stools), epigastric pain, bloating, nausea, diminished interest in food, possible (but rare) vomiting which is often violent, and weight loss. Pus, mucus and blood are occasionally present in the stool. It usually causes "explosive diarrhea" and while unpleasant, is not fatal. In healthy individuals, the condition is usually self-limiting, although the infection can be prolonged in patients who are immunocompromised, or who have decreased gastric acid secretion.
Treatment and diagnosis
G. lamblia infection in humans is frequently misdiagnosed. Accurate diagnosis requires an antigen test or, if that is unavailable, an ova and parasite examination of stool. Multiple stool examinations are recommended, since the cysts and trophozoites are not shed consistently. Given the difficult nature of testing to find the infection, including many false negatives, some patients should be treated on the basis of empirical evidence, treating based on symptoms.
Human infection is conventionally treated with metronidazole, tinidazole or nitazoxanide. Although metronidazole is the current first-line therapy, it is mutagenic in bacteria and carcinogenic in mice, so should be avoided during pregnancy. It has not directly been linked to causing cancer in humans, only in other mammals, therefore appears safe. One of the most common alternative treatments is berberine sulfate (found in Oregon grape root, goldenseal, yellowroot, and various other plants). Berberine has been shown to have an antimicrobial and an antipyretic effect. Berberine compounds cause uterine stimulation, and so should be avoided in pregnancy. Continuous high dosing of berberine may lead to bradycardia and hypotension in some individuals.
|Drug||Treatment duration||Possible side effects|
|Metronidazole||5–7 days||Metallic taste; nausea; vomiting; dizziness; headache; disulfiram-like effect; neutropenia|
|Tinidazole||Single dose 2 000 mg.||Metallic taste; nausea; vomiting; belching; dizziness; headache; disulfiram-like effect|
|Nitazoxanide||3 days||Abdominal pain; diarrhea; vomiting; headache; yellow-green discolouration of urine|
|Albendazole||5 days||Dizziness; headache; fever; nausea; vomiting; temporary hair loss|
Table adapted from Huang, White.
Treatment in animals
Cats can be cured easily and lambs usually simply lose weight, but in calves, the parasites can be fatal and often are not responsive to antibiotics or electrolytes. Carriers among calves can also be asymptomatic. This parasite is deadly for chinchillas, so extra care must be taken by providing them with safe water. Dogs have a high infection rate, as 30% of the population under one year old are known to be infected in kennels. The infection is more prevalent in puppies than in adult dogs. Infected dogs can be isolated and treated, or the entire pack at a kennel can be treated together regardless. Kennels should also be then cleaned with bleach or other cleaning disinfectants. The grass areas used for exercise should be considered contaminated for at least one month after dogs show signs of infection, as cysts can survive in the environment for long periods of time. Prevention can be achieved by quarantine of infected dogs for at least 20 days and careful management and maintenance of a clean water supply.
Under a normal compound light microscope, Giardia often looks like a "clown face," with two nuclei outlined by adhesive discs above dark median bodies that form the "mouth." Cysts are oval, have four nuclei, and have clearly visible axostyles. In spite of the common belief that all eukaryotes have mitochondria, Giardia is one of the few to lack these organelles, but they contain a mitochondrial relics, called mitosomes. However, similar to other eukaryotes, Giardia contains a complex endomembrane system as well as a tubulin based cytoskeleton. Immunoelectron microscopy with antibody to alpha-tubulin shows that microtubules are present in Giardia in different structures such as axonemes, basal bodies, adhesive disk, funis and the median bodies.
Giardia alternates between two different forms — a hardy, dormant cyst that contaminates water or food, and an active, disease-causing form that emerges after the parasite is ingested. Dr. Frances Gillin of the University of California, San Diego and her colleagues cultivated the entire life cycle of this parasite in the laboratory, and identified biochemical cues in the host's digestive system which trigger Giardia's life cycle transformations. They also uncovered several ways in which the parasite evades the defences of the infected organism. One of these is by altering the proteins on its surface, which confounds the ability of the infected animal's immune system to detect and combat the parasite (called antigenic variation). Gillin's work reveals why Giardia infections are extremely persistent and prone to recur. In addition, these insights into its biology and survival techniques may enable scientists to develop better strategies to understand, prevent, and treat Giardia infections.
In December 2008, Nature published an article showing the discovery of an RNA interference mechanism that allows Giardia to switch variant-specific surface proteins to avoid host immune response. The discovery was made by the team working at the Biochemistry and Molecular Biology Laboratory, School of Medicine, Catholic University of Cordoba, Argentina, led by Dr. Hugo Lujan.
Giardia and the other diplomonads are unique in their possession of two nuclei that are similar in appearance, DNA content, transcription and time of replication. There are five chromosomes per the haploid genome. The genome has been sequenced and was published in 2007, although the sequence contains several gaps. The sequence is about 12 million base pairs and contains about 5000 protein-coding genes. The GC content is 46%. Trophozoites have a ploidy of four and the ploidy of cysts is eight, which in turn raises the question of how Giardia maintains homogeneity between the chromosomes of the same and opposite nuclei. Modern sequencing technologies have been used to resequence different strains.
Giardia had been assumed to be primitively asexual and with no means of transferring DNA between nuclei. These assumptions made it very difficult to explain the remarkably low level of allelic heterozygosity (< 0.01%) in the genome isolate, WB. However, all those assumptions of asexuality are now in doubt, with population genetics providing evidence for recombination and the identification of meiotic genes, evidence for recombination among isolates and the evidence for exchange of genetic material between nuclei during the process of encystation.
These findings on sexuality in Giardia, above, have important implications for understanding the origin of sexual reproduction in eukaryotes. Even though sexual reproduction is widespread among extant eukaryotes, it seemed unlikely, until recently, that sex is a primordial and fundamental feature of eukaryotes. A probable reason for the view that sex may not be fundamental to eukaryotes was that sexual reproduction previously appeared to be lacking in certain human pathogenic single-celled eukaryotes (e.g. Giardia) that diverged from early ancestors in the eukaryotic lineage.
In addition to the evidence cited above for recombination in Giardia, Malik et al. reported that many meiosis specific genes occur in the Giardia genome, and further that homologs of these genes also occur in another unicellular eukaryote, Trichomonas vaginalis. Because these two species are descendants of lineages that are highly divergent among eukaryotes, Malik et al. suggested that these meiotic genes were present in a common ancestor of all eukaryotes. Thus, on this view, the earliest ancestor of eukaryotes was likely capable of sexual reproduction. Furthermore, Dacks and Roger  proposed, based on phylogenetic analysis, that facultative sex was present in the common ancestor of all eukaryotes. Bernstein et al. also reviewed evidence in support of this view.
Seven genotypes of Giardia have been recognized to date (A-G). Of these, B is the most widespread. Only types A and B have been shown to be infectious to humans.
Van Leeuwenhoek's observations were recreated, using a single-lens microscope of the kind he used, by British microbiologist Brian J. Ford, who showed how clearly one could view Giardia through a primitive microscope.
In 1998, a highly publicised Giardia and Cryptosporidium outbreak was reported in Sydney, Australia, but it was found to be due to mismeasurement of the concentrations of microbes in the water supply. A 2004 outbreak in Bergen (Norway) hastened work on adding UV treatment to the water facilities.
In October 2007, Giardia was found in the water supply for parts of Oslo, prompting authorities to advise the public to boil drinking water; but subsequent test showed levels of contamination too low to pose a threat, so this advice has since been cancelled.
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