Giardiasis
Giardiasis is a parasitic disease caused by the protist enteropathogen Giardia duodenalis, especially common in children and travelers. Infected individuals experience steatorrhea, a type of diarrhea with fatty sticky stool; abdominal pain, weight loss, and weakness due to dehydration and malabsorption. Less common symptoms include skin rash, hives and joint swelling. Symptoms usually begin one to three weeks after exposure and, without treatment, may last two to six weeks or longer. Some infected individuals experience mild or no symptoms and remain symptom-free even if the infection persists for a long time.
Giardiasis spreads via the fecal-oral route, when Giardia cysts excreted with feces contaminate food or water that is later consumed orally. The disease can also spread between people and between people and animals, mainly via pets. Cysts may survive for nearly three months in cold water.
The microscopic identification of Giardia and its cysts in fecal samples is considered the gold standard method for diagnosing giardiasis. Immunoassays, such as ELISA and PCR for giardia gene loci, are also available as diagnostic tools, although are not widely used due to methods complexity and costs.
Prevention may be improved through proper personal hygiene practices and by cooking and sanitizing food. Asymptomatic cases often do not need treatment. When symptoms are present, treatment is typically provided with either tinidazole or metronidazole. Other drugs, such as nitazoxanide, albendazole, quinacrine, chloroquine, paromomycin, and other drug combinations are also used in clinics. Refractory giardiasis and resistant strains are reported more and more often. Infection may cause a person to become lactose intolerant, so it is recommended to temporarily avoid lactose following an infection or use lactase supplements.
Giardiasis occurs worldwide. It is one of the most common parasitic human diseases. Infection rates are as high as 7% in the developed world and 30% in the developing world. In 2013, there were approximately 280 million people worldwide with symptomatic cases of giardiasis. The World Health Organization classifies giardiasis as a neglected disease. It is popularly known as beaver fever in North America.
Signs and symptoms
The signs and symptoms vary from none to severe diarrhoea with poor nutrient absorption. The cause of this wide range in severity of symptoms is not fully known, but the intestinal flora of the infected host may play a role. Diarrhoea is less likely to occur in people from developing countries.Symptoms typically develop 9–15 days after exposure, but may occur as early as one day. The most common and prominent symptom is chronic diarrhoea, which can occur for weeks or months if untreated. Diarrhoea is often greasy and foul-smelling, with a tendency to float. This characteristic diarrhoea is often accompanied by several other symptoms, including gas, abdominal cramps, and nausea or vomiting. Some people also experience symptoms outside of the gastrointestinal tract, such as itchy skin, hives, and swelling of the eyes and joints, although these are less common. Fever occurs in only about 15% of infected people, despite the nickname "beaver fever".
Prolonged disease is often characterised by chronic diarrhoea and malabsorption of nutrients in the intestine. This malabsorption causes fatty stools, substantial weight loss, and fatigue. Additionally, those with giardiasis often have difficulty absorbing lactose, vitamin A, folate, and vitamin B12. In children, prolonged giardiasis can cause failure to thrive and may impair mental development. Symptomatic infections are well recognised as causing lactose intolerance, which, though usually temporary, may become permanent.
Cause
Giardiasis is caused by the protozoan Giardia duodenalis. The infection occurs in many animals, including pets, beavers, other rodents, cows, and sheep. Animals are believed to play a role in keeping infections present in an environment.G. duodenalis has been sub-classified into eight genetic assemblages. Genotyping of G. duodenalis isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main and possibly only G. duodenalis assemblages that infect humans.
Risk factors
According to the United States Centers for Disease Control and Prevention, people at greatest risk of infection are:- People in childcare settings
- People who are in close contact with someone who has the disease
- Travellers within areas that have poor sanitation
- People who have contact with faeces, such as during sexual activity
- Backpackers or campers who drink untreated water from springs, lakes, or rivers
- Swimmers who swallow water from swimming pools, hot tubs, interactive fountains, or untreated recreational water from springs, lakes, or rivers
- People who get their household water from a shallow well
- People with weakened immune systems
- People who have contact with infected animals or animal environments contaminated with faeces
Transmission
Giardiasis is transmitted via the faecal-oral route with the ingestion of cysts. Primary routes are personal contact and contaminated water and food. The cysts can stay infectious for up to three months in cold water. Both symptomatic and asymptomatic carriers excrete cysts and thus spread the disease.Pathophysiology
The life cycle of Giardia consists of a cyst form and a trophozoite form. The cyst form is infectious and once it has found a host, it transforms into the trophozoite form. This trophozoite attaches to the intestinal wall and replicates within the gut. As trophozoites continue along the gastrointestinal tract, they convert back to their cyst form, which is then excreted with faeces. Ingestion of only a few of these cysts is needed to generate infection in another host.Infection with Giardia results in decreased expression of brush border enzymes, morphological changes to the microvillus, increased intestinal permeability, and programmed cell death of small intestinal epithelial cells. Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it.
The attachment of trophozoites causes villous flattening and inhibition of enzymes that break down disaccharide sugars in the intestines. Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhoea, one of the predominant symptoms. In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases varies greatly.
The species Giardia intestinalis uses enzymes that break down proteins to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host T lymphocytes attack endothelial cells that have been injured to remove the cells. This occurs after the disruption of proteins that connect brush border endothelial cells to one another. The result is increased intestinal permeability.
There appears to be a further increase in programmed enterocyte cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability. There is significant upregulation of the programmed cell death cascade by the parasite, and substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.
Giardia protects its growth by reducing the formation of the gas nitric oxide by consuming all local arginine, which is the amino acid necessary to make nitric oxide. Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.
Antigenic variation and immune evasion
Giardia lamblia evades host immunity through antigenic variation of its variant-specific surface proteins. Giardia’s trophozoite genome contains more than 200 VSPs, but only one VSP is displayed on the trophozoite’s surface at any given time. RNA interference suppresses all but one VSP mRNA, which results in only one VSP being expressed on the surface of the trophozoite.When switching occurs the previously expressed VSP disappears and a different VSP mRNA bypasses the RNAi suppressing and results in the expression of the new VSP on the trophozoites surface allowing the parasite to evade immunity.