Giardiasis

Signs and symptoms

Symptoms vary from none to severe diarrhea with poor absorption of nutrients. It can result in weakness, loss of appetite, stomach cramps, vomiting, bloating, excessive gas, and burping. Symptoms typically develop 9–15 days after exposure, but may occur as early as one day.

Symptoms are caused by Giardia organisms infecting the cells of the duodenum and jejunum of the small intestine and blocking nutrient absorption. Most people are asymptomatic; only about a third of those infected exhibit symptoms. If the infection is not treated, these symptoms may last for six weeks or more.

Symptomatic infections are well recognized as causing lactose intolerance, which, while usually temporary, may become permanent. Although hydrogen breath tests indicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection. It has been suggested that these observations are explained by symptomatic giardia infection allowing for the overgrowth of other bacteria.

Some studies have shown giardiasis should be considered as a cause of vitamin B₁₂ deficiency as a result of the problems caused within the intestinal absorption system.

Cause

Giardiasis is caused by the protozoan Giardia lamblia. The infection occurs in many animals including beavers (hence its nickname), as well as cows, rodents, 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 (designated A–H). 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 (or possibly only) G. duodenalis assemblages that undeniably infect humans.

Risk factors

According to the CDC, "Those at greatest risk are travelers to countries where giardiasis is common, people in child care settings, those who are in close contact with someone who has the disease, people who swallow contaminated drinking water, backpackers or campers who drink untreated water from lakes or rivers, people who have contact with animals who have the disease, and men who have sex with men."

In the United States, giardiasis occurs more often during the summer. This is believed to be due to a greater amount of time spent on outdoor activities and traveling in the wilderness.

Transmission

Giardiasis is transmitted via the fecal-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.

Not all Giardia infections are symptomatic, and many people can unknowingly serve as carriers of the parasite.

Pathophysiology

Giardia are flagellated protozoans that cause decreased expression of brush border enzymes, morphological changes to the microvillus, and programmed cell death of small intestinal epithelial cells. There is no invasion of giardia trophozoites, and small intestinal morphology may appear normal in light microscopy.

The attachment of trophozoites causes villus 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 diarrhea, 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 is highly varied.

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 in order to remove the cell. This occurs after the disruption of proteins that connect brush border endothelial cells to one another. The result is heavily increased intestinal permeability.

There appears to be a further increase in programmed 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, furthermore, 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 own 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.

Diagnosis

Prevention

The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water.

Boiling suspect water for one minute is the surest method to make water safe to drink and kill disease-causing microorganisms such as Giardia lamblia if in doubt about whether water is infected. Chemical disinfectants or filters may be used.

According to a review of the literature from 2000, there is little evidence linking the drinking of water in the North American wilderness and Giardia. The researcher notes that treatment of drinking water for Giardia may not be as important as recommended hand-washing in wilderness regions in North America. CDC surveillance data (for 2005 and 2006) reports one outbreak (6 cases) of waterborne giardiasis contracted from drinking wilderness river water in Colorado. However, less than 1% of reported giardiasis cases are associated with outbreaks.

Treatment

Treatment is not always necessary as the infection usually resolves on its own. However, if the illness is acute or symptoms persist and medications are needed to treat it, a nitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.

The World Health Organization and Infectious Disease Society of America recommend metronidazole as first line therapy. 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 done by the Cochrane Collaboration 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 10 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. While tinidazole has similar side effects and efficacy to metronidazole, it is administered with a single dose.

Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories so is theoretically possible. The exact mechanism of resistance to all of these medications is not well understood. In the case of nitroimidazole-resistant strains of Giardia, other drugs are available which have showed efficacy in treatment including quinacrine, nitazoxanide, bacitracin zinc, furazolidone and paromomycin.

During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, and thus less exposure to the fetus. Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy.

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.

Research

Some intestinal parasitic infections may play a role in irritable bowel syndrome and other long-term sequelae.