Giardiasis

The signs and symptoms vary from none to severe diarrhoea with poor nutrient absorption. Diarrhoea is less likely to occur in people from developing countries. 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 (steatorrhea) is often accompanied by several other symptoms, including gas, abdominal cramps, and nausea or vomiting. despite the nickname "beaver fever". which, though usually temporary, may become permanent. ==Cause==

Giardiasis is caused by the protozoan Giardia duodenalis. Risk factors According to the United States Centers for Disease Control and Prevention (CDC), 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 Factors that increase infection risk for people from developed countries include changing nappies/diapers, consuming raw food, owning a dog, and travelling in the developing world. Primary routes are personal contact and contaminated water and food. ==Pathophysiology==

The life cycle of Giardia consists of a cyst form and a trophozoite form. 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. Antigenic variation and immune evasion Giardia duodenalis evades host immunity through antigenic variation of its variant-specific surface proteins (VSPs). ''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 (RNAi) 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. == Host defence ==

Host defence against Giardia consists of natural barriers, production of nitric oxide, and activation of the innate and adaptive immune systems. Natural barriers Natural barriers defend against the parasite entering the host's body. Natural barriers consist of mucus layers, bile salt, proteases, and lipases. Additionally, peristalsis and the renewal of enterocytes provide further protection against parasites. Nitric oxide production Nitric oxide does not kill the parasite, but it inhibits the growth of trophozoites as well as excystation and encystation. Innate immune system Lectin pathway of complement The lectin pathway of complement is activated by mannose-binding lectin (MBL), which binds to N-acetylglucosamine. N-acetylglucosamine is a ligand for MBL and is present on the surface of Giardia. The classical pathway of complement The classical pathway of complement is activated by antibodies specific against Giardia. Adaptive immune system Antibodies Antibodies inhibit parasite replication and also induce parasite death via the classical pathway of complement. Infection with Giardia typically results in a strong antibody response against the parasite. While IgG is made in significant amounts, IgA is believed to be more important in parasite control. IgA is the most abundant isotype in intestinal secretions, and it is also the dominant isotype in a mother's milk. Antibodies in a mother's milk protect children against giardiasis (passive immunisation). T-cells The major aspect of adaptive immune responses is the T-cell response. Giardia is an extracellular pathogen. Therefore, CD4+ helper T-cells are primarily responsible for this protective effect. One role of helper T-cells is to promote antibody production and isotype switching. Other roles include cytokine production (IL-4, IL-9) to help recruit other effector cells of the immune response. ==Diagnosis==

ed sample. • According to the CDC, the detection of antigens on the surface of organisms in stool specimens is the current test of choice for the diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques. • A trichrome stain of preserved stool is another method used to detect Giardia. • Microscopic examination of the stool can be performed for diagnosis. • Immunologic enzyme-linked immunosorbent assay (ELISA) testing may be used for diagnosis. Although hydrogen breath tests indicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection. Serological tests are not helpful in diagnosis. ==Prevention==

The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water. Boiling water contaminated with Giardia effectively kills infectious cysts. Chemical disinfectants or filters may be used. Iodine-based disinfectants are preferred over chlorination as the latter is ineffective at destroying cysts. Although the evidence linking the drinking of water in the North American wilderness and giardiasis has been questioned, several studies raise concerns. Most if not all CDC verified backcountry giardiasis outbreaks have been attributed to water. Surveillance data (for 2013 and 2014) reports six outbreaks (96 cases) of waterborne giardiasis contracted from rivers, streams or springs and less than 1% of reported giardiasis cases are associated with outbreaks. Person-to-person transmission accounts for the majority of Giardia infections and is usually associated with poor hygiene and sanitation. Giardia is often found on the surface of the ground, in the soil, in undercooked foods, and in water, and on hands that have not been properly cleaned after handling infected faeces. Water-borne transmission is associated with the ingestion of contaminated water. In the U.S., outbreaks typically occur in small water systems using inadequately treated surface water. Venereal transmission happens through faecal-oral contamination. Additionally, nappy/diaper changing and inadequate handwashing are risk factors for transmission from infected children. Lastly, food-borne epidemics of Giardia have developed through the contamination of food by infected food handlers. Vaccine There are no vaccines for humans; however, several vaccine candidates are in development. They are targeting: recombinant proteins, DNA vaccines, variant-specific surface proteins (VSP), cyst wall proteins (CWP), giadins, and enzymes. Researchers at CONICET have produced an oral vaccine after engineering customised proteins mimicking those expressed on the surface of Giardia trophozoites. The vaccine has proven effective in mice. One commercially available vaccine exists – GiardiaVax, made from G. duodenalis whole trophozoite lysate. It is a vaccine for veterinary use only in dogs and cats. GiardiaVax should promote the production of specific antibodies. ==Treatment==

Treatment is not always necessary as the infection usually resolves on its own. The US CDC lists metronidazole, tinidazole, and nitazoxanide as effective first-line therapies; of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA. A meta-analysis published by the Cochrane Collaboration in 2012 found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues. Other meta-analyses have reached similar conclusions. Both medications need a five to ten-day-long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole, or nitazoxanide was felt to be of very low quality. The exact mechanism of resistance to all of these medications is not well understood. During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, resulting in less exposure to the foetus. Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy. ==Prognosis==

In people with a properly functioning immune system, infection may resolve without medication. Children with chronic giardiasis are at risk for failure to thrive as well as more long-lasting sequelae such as growth stunting. Up to half of infected people develop a temporary lactose intolerance leading to symptoms that may mimic a chronic infection. Some people experience post-infectious irritable bowel syndrome after the infection has cleared. Giardiasis has also been implicated in the development of food allergies. This is thought to be due to its effect on intestinal permeability. ==Epidemiology==

In some developing countries Giardia is present in 30% of the population. In the United States it is estimated that it is present in 3–7% of the population. Transmission is common in areas with inadequate sanitation and restricted access to clean water, primarily affecting children with low access to resources. The number of reported cases in the United States in 2018 was 15,584. All states that classify giardiasis as a notifiable disease had cases of giardiasis. July, August, and September are the months with the highest incidence of giardiasis in the United States. In the ECDC's (European Centre for Disease Prevention and Control) annual epidemiological report containing 2014 data, 17,278 confirmed giardiasis cases were reported by 23 of the 31 countries that are members of the EU/EEA. ==Research==

Some intestinal parasitic infections may play a role in irritable bowel syndrome and other long-term sequelae such as chronic fatigue. The mechanism of transformation from cyst to trophozoites has not been characterised The main congress about giardiasis is the "International Giardia and Cryptosporidium Conference" (IGCC). A summary of results presented at the most recent edition (2019, in Rouen, France) is available. ==Other animals==

In both cats and dogs, giardiasis usually responds to metronidazole and fenbendazole. Metronidazole in pregnant cats can cause developmental malformations. Giardiasis has been shown to decrease weight in livestock. == One Health Perspective ==

Giardiasis is an example of a One Health issue that reflects the interconnected relationship between humans, animals, and environmental health. Giardia duodenalis is a parasite that affects several hosts including humans, domestic animals, and wildlife. Environmental contamination occurs through infected animals' fecal shedding of cysts, which may persist in water and soil for long periods of time. Agricultural runoff and hazardous sanitation measures are major routes of transmission that contaminate water sources. == References ==