In the US, and likely in many other temperate developed areas, the epidemiology is very different from what is found in the tropics. Infections frequently occur as water-borne outbreaks and the percent of people with symptomatic disease appears much higher Many of the cases are the result of recreational water use, which is thought to explain the two-fold increase in cases from June through October.
The incidence is several-fold higher in children ages one to nine especially one to four , which could be due to day care exposure, more frequent recreational water exposure, and the lack of protection acquired from prior exposure. Less commonly, outbreaks have been associated with food ingestion, either as a result of an infected food handler or by handling food after changing diapers for an infected child , , Men who have sex with men also appear to be at increased risk of giardiasis , Household pets have been proposed as potential sources of human giardiasis, but there are no convincing reports of transmission of giardiasis from dogs or cats to humans.
Since these animals usually carry genotypes that differ from those found in humans, it is likely that cross-transmission does not occur frequently. Case rates per , population vary from 1. Giardiasis is substantially underdiagnosed, so the rate of 7 per , is a substantial underestimate. In contrast, the rates determined from fecal specimens are generally from symptomatic patients, resulting in a marked overestimate by this approach.
The rate of hospitalization for giardiasis has been estimated at 2 per ,, which is similar to that of shigellosis After ingestion of G. The presence or absence of symptoms after infection varies greatly with the type of population. The reasons for these differences are not well understood, but it is likely that at least part of the difference is a reflection of partial immunity that protects from symptomatic disease.
This possibility is supported by an outbreak in a ski resort in Colorado in which the clinical attack rate was much higher for tourists than for local residents despite drinking the same water the source of infection The local residents had probably had prior exposure and developed protection from symptomatic disease.
In contrast, the symptomatic patients in some of the clinical trials for treatment of giardiasis had much lower rates of diarrhea. Thus, even among symptomatic patients the clinical presentation varies significantly according to patient selection. In contrast to the high attack rates found in nonendemic regions, symptoms are the exception rather than the rule in highly endemic regions and case controlled studies have frequently found no correlation between Giardia infection and symptoms.
Some have even suggested a protective role for Giardia in that setting The relative importance of the organism, host genetics, host microbiota and pre-existing immunity remain to be determined. The diagnosis of giardiasis is generally made by the identification of cysts or trophozoites in fecal specimens standard ova and parasite examination. Trophozoites are found less frequently, but may be more associated with symptomatic infection.
Shedding of cysts is somewhat intermittent, so a total of three fecal samples over a period of several days is generally recommended. Fecal coproantigen detection using enzyme immunoassays EIA or immunochromography detection and fluorescent antibody FA assays of fecal specimens are being used increasingly 60 , 75 , 76 , , , , , , , , These methods all provide increased sensitivity so that one fecal sample is probably comparable to three samples used for ova and parasite identification.
The FA test provides combined diagnosis of Giardia and Cryptosporidium , and is slightly more sensitive and specific, while the coproantigen detection methods are much less labor-intensive.
Nucleic acid detection methods have also been studied extensively and include conventional and real time PCR as well asLoop mediated isothermalamplification LAMP 94 , Nucleic acid methods probably have greater sensitivity but questions remain regarding their specificity. Perhaps a greater sensitivity is allowing the detection of low levels of infection that are not associated with clinical manifestations.
In addition, nucleic acid detection tests are more expensive and laborious than immunologic methods and have not yet gained widespread usage in clinical settings. There are some patients with chronic diarrhea and malabsorption consistent with giardiasis who have repeatedly negative fecal examinations.
In some of these patients, Giardia trophozoites can be identified by endoscopic aspiration from the small intestine 97 , This approach has the advantage that a biopsy can be done to identify other etiologies of malabsorption such as celiac disease or Whipple's disease.
Alternatively, the string test can be used 84 , With this approach, the patient swallows a string with a capsule on the end for four hours to overnight. The end of the string is then examined microscopically for the presence of Giardia trophozoites.
Whether these patients could be identified by PCR has not been systematically evaluated. There are no antibody or antigen-based serologic assays available for the diagnosis of giardiasis. Infection is initiated when the cyst is ingested from a fecally contaminated environmental source.
The cyst is the environmentally stable and nearly inert form of the organism and can remain viable for up to a month in a moist environment at 4 o C. The survival is less at higher temperatures and in dryer climates, perhaps explaining why the US prevalence is higher in the northern than in the southern states Patent infection can be initiated by the ingestion of as few as 10 cysts Excystation into trophozoites is triggered during passage through the gastric acid of the stomach and into the bile-rich duodenum However, it should be noted that the acidic environment is not required as demonstrated by in vitro excystation under conditions of neutral pH 68 as well as the observation that gastric acidity does not protect from infection.
The trophozoite is the vegetative form of the parasite, which then colonizes the surface of the small intestine and causes the associated symptoms. The ventral surface of the trophozoite consists of a concave surface that attaches to the intestinal, most likely via a suction generated by the ventral disk 59 , 90 , Although receptor-based attachment has been proposed, the organisms attach nearly as well to smooth inanimate objects such as glass nearly as well as to intestinal mucosa, emphasizing the primary importance of the physical attachment.
Trophozoites have 4 pairs of flagella, providing the motility required within the small intestine. The mechanism s by which Giardia causes diarrhea and malabsorption are not yet well understood. There is evidence for villous flattening with epithelial barrier dysfunction and impaired epithelial transport However, the mechanism by which this occurs is unclear since no toxin has been identified and the degree of inflammatory response is relatively limited In contrast, trophozoites may actually attenuate the immune response as well A study using an in vitro model of Giardia trophozoites both Genotypes A and B showed that they adhered to Caco-2 cells under the control of the trophozoite lipid raft Adhesion resulted in disorganization of the F-actin cytoskeleton, followed by losses of numerous functional brush border proteins.
Thus, direct and immunopathogenic mechanisms may be important. In addition, a recent study using an adult mouse model and Genotype B isolates showed symptomatic disease in mice that was accentuated by malnutrition, suggesting possible parallels with human infections The antibody-mediated secretory immune response has long been considered the major means of host response and elimination of the infection based in increased prevalence and severity in patients with hypogammaglobulinemia and possibly with isolated IgA deficiency.
However, evidence from an animal model of giardiasis suggests that the cell mediated immune response may also be an important contributor Trophozoites are coated by a cysteine-rich protein that undergoes antigenic variation in vitro 2 , in an animal model 5 , and in human volunteers, which may contribute to the prolonged infections that are typical of giardiasis.
Trophozoites replicate by binary fission in the small intestine, and until recently, Giardia has been assumed to be asexual. However, population genetic evidence for recombination among different organisms within a single genotype suggests a sexual or parasexual cycle of replication 40 , There is evidence for exchange of nuclear contents within single encysting organisms 37 , , so perhaps encystation also provides an occasional means of exchanging genetic material between organisms.
More distally in the small intestine, some of the trophozoites are differentiated into cysts, a process which is triggered either by exposure to certain increased bile concentration and a slightly alkaline pH or possibly due to cholesterol starvation Encystation occurs during binary fission of the trophozoite after partial completion of cytokinesis, so that a cyst has four nuclei and will release two trophozoites after subsequent excystation in the next host.
However, it should be recognized that these studies are much more difficult than those used for most bacteria, and even in comparison to the yeasts. These difficulties result from the requirement for anaerobic growth and the slow generation time hours. In addition, these studies must be done with laboratory-adapted strains since axenization adaptation to in vitro cultivation without other organisms is laborious and not always successful.
A variety of different methods have been used to assay drug susceptibility. A mouse model for susceptibility has even been used to circumvent the difficulty of axenizing Giardia Methods using growth inhibition versus loss of adherence give varying results for different classes of drugs, supporting the proposition that direct comparison of results across classes of antimicrobial agents is inappropriate Another in vitro approach determined the degree of growth inhibition after two days of drug exposure in comparison to untreated trophozoites.
Aminoglycoside susceptibilities were correlated with the Giardia rDNA sequence, which predicted the activity of paromomycin and hygromycin against Giardia , but the lack of activity for other aminoglycosides such as gentamicin 54 , The same approach was used to show the activity of the benzimidazoles 56 and some activity for the more lipophilic tetracyclines, such as doxycycline More recently, loss of viability as determined by loss of parasite motility has been used to identify nitroimidazoles with activity against organisms that have reduced in vitro susceptibility to metronidazole The tricyclic, 3-chloroimipramine, also has anti- Giardia activity A variety of natural and synthetic flavonoids have demonstrated in vitro activity against Giardia as reviewed in Some of these agents were identified on the basis of their roles as natural remedies for gastrointestinal illnesses, and in some cases, the activity is greater than that of metronidazole Numerous recent studies have analyzed the in vitro effects of a variety of agents against Giardia , including analogs of drugs known to be active, plant materials and other agents 8 , 21 , 28 , 29 , 30 , 31 , 32 , 48 , 49 , 50 , 57 , 58 , 74 , 92 , 93 , 99 , , , , , , , , , , , , , , , , , , , , , , Methods with higher throughput have also been used to identify bioactive compounds with in vitro activity against Giardia , , Several of the studies of drug resistance have demonstrated the ability to develop laboratory strains that have markedly reduced susceptibility to metronidazole or albendazole.
Since , the most studied drugs in numbers of studies and patients have been metronidazole, tinidazole, and albendazole see Table 2 for a list of drugs used for treatment of giardiasis. These drugs have all had excellent side effect profiles. The efficacies of metronidazole and tinidazole have been uniformly excellent, while some studies of albendazole have shown inferiority to the nitroimidazoles.
Therefore, metronidazole and tinidazole should be considered the drugs of choice. Of the two, tinidazole is effective when given as a single dose, greatly improving the ease of administration and compliance in comparison to metronidazole. However, the cost may be greater than generic forms of metronidazole, limiting its availability in some areas. Secnidazole and ornidazole appear to be as effective as tinidazole, but have been studied less and are not available in the US.
Albendazole probably has the most favorable side effect profile and may be an optimal choice when its anti-helminthic activity is desired. Quinacrine is difficult to obtain in the US and treatment is more likely to be limited by toxicity, but the drug if highly effective and may be especially useful in combination with a nitroimidazole for refractory cases of giardiasis.
Numerous trials have been conducted to determine the comparative efficacies of different treatment regimens Table 3. The studies included in the table include most of the comparative trials that have been reported in English-language articles since that are indexed on Medline.
Many of the studies have been included in recent systematic reviews or meta-analyses 85 , , Table 3. The more recent studies were identified surveying all articles with the key word of giardiasis that reported comparative trials. Most of the studies have one or more significant flaws, such as small numbers, inadequate follow-up, or non-standard treatment regimens, Very few of the studies were placebo-controlled, but for those that were, the spontaneous resolution of Giardia cyst excretion, was relatively uncommon.
Most of the studies have been performed in developing countries that are endemic for giardiasis, but a few have been performed in the US and other western countries.
The majority of studies included only symptomatic patients, but a substantial minority included asymptomatic patients as well. When the percentage of symptomatic patients was available, it was included in the table. However, despite the limitations, the relatively large number of studies makes it possible to glean valuable information from these reports.
Some of the key points are as follows:. All except metronidazole i. For metronidazole, a number of studies have demonstrated rather poor efficacy after single dose, but longer courses have been very successful.
The side effect profiles have been similar for all agents with gastrointestinal side effects being very common, but serious side effects are rare. In addition, mebendazole has shown quite poor efficacy in some of the studies. In general, these drugs have been very well tolerated. Not only have they been without serious side effects in these studies; they lack the transient gastrointestinal side effects that are common with the nitroimidazoles.
That means that for any drug treatment course, there is the possibility of clinical failure, which is not necessarily the result of drug resistance. Nitroimidazoles: The nitroimidazoles have a rather unique mechanism of action that results in broad spectrum activity against anaerobic protozoa and bacteria.
In the setting of an anaerobic or microaerophilic environment, pyruvate:ferredoxin oxidoreductase PFOR reduces ferredoxin or flavodoxin, which then donates an electron to metronidazole or another nitroimidazole , activating the drug within the cell. The reduced drug becomes a toxic radical which covalently binds to DNA The DNA destruction is proposed as the mechanism of killing, although cellular proteins may also be affected. The validity of this proposed mechanism in Giardia is supported by studies in which transfection was used to inhibit PFOR expression in Giardia , resulting in increased survival in oxygen and decreased susceptibility to metronidazole These drugs are mutagenic in vitro , which led to their delayed acceptance as therapeutic agents, but carcinogenesis in humans has not been documented Metronidazole and tinidazole are both available in the US, although metronidazole has never been approved for treatment of giardiasis.
Serious side effects are rare with these drugs, and all have similar side effect profiles which include a metallic taste in the mouth, nausea and vomiting, and anorexia. In addition, there is a potential disulfiram-like interaction with alcohol, so ethanol ingestion is prohibited during treatment.
Metronidazole: is the most studied drug for treatment of giardiasis and is available worldwide at low costs. Useful reviews of pharmacology and mechanism have been published 72 , Treatment courses ranging from single dose to 10 days have been used. These day courses have generally used doses of mg to mg tid for adults, or the equivalent dose for children.
It is not clear whether the higher dose results in significantly improved outcomes. Tinidazole: has been used worldwide for decades and recently became available in the United States Tinidazole has also been evaluated in numerous studies, but in contrast to metronidazole, these have almost exclusively been as single dose treatment courses.
Secnidazole and ornidazole are other nitroimidazoles with pharmacokinetic properties similar to those of tinidazole. These agents have also been studied primarily in single dose treatment courses Benzimidazoles: The benzimidazoles are broad spectrum anti-helminthic agents that bind to beta-tubulin, causing irreversible damage to the parasite They are poorly absorbed from the gastrointestinal tract of humans, but absorption is improved by food ingestion, especially with a high fat content These agents are embryotoxic in animals, causing a craniofacial abnormality, although at higher blood levels than have documented in humans.
It is the most extensively studied benzimidazole and has yielded the best clinical response rates Table 3. In addition, albendazole has been very well tolerated with low rates of side effects. In general, the response rates have been unsatisfactory. Nitazoxanide: Nitazoxanide is a relatively new antimicrobial agent that has activity for Giardia in addition to E.
After absorption from the gastrointestinal tract, the drug is very rapidly converted to its active metabolite, tizoxanide, so that the parent drug cannot be detected in the serum. Nitazoxanide is proposed to work as a noncompetitive inhibitor of the PFOR reaction 95 perhaps by inhibiting the binding of pyruvate to the thiamine pyrophosphate cofactor It is approved in the US for treatment of giardiasis in children and adults. Furazolidone: Furazolidone is a nitrofuran that became popular for treating giardiasis in children because of its better tolerability than quinacrine and because it is available in liquid suspension The drug is well absorbed orally and has a half life of about 10 minutes.
It has a broad spectrum of antimicrobial activity, including gram positive and gram negative aerobic bacteria. The toxicity of the metabolites is mediated via DNA binding and destruction. Serious toxicity has been rare, but the drug is mutagenic in bacteria and carcinogenic in animals.
It has been administered 4 times daily for 7 to 10 days. Quinacrine: Quinacrine was developed as an antimalarial agent, and for many years was considered the treatment of choice for giardiasis in the US The drug is well absorbed from the gastrointestinal tract and has a half life of days. The drug intercalates with the DNA of the trophozoite, but does not localize to the nuclei, so the mechanism of inhibition of trophozoites is unclear. It also reduces cyst viability Perhaps the most troubling toxicity has been the occasional report of toxic psychosis.
A bitter taste and vomiting are common, especially in children, sometimes limiting its efficacy. It is no longer generally available in the US, but is available from a compounding pharmacy see Table 2. In most studies, the drug was given in three doses per day for 5 to 10 days. Two studies have observed that the efficacy of quinacrine combined with another agent metronidazole was very high for cases of refractory giardiasis , see Treatment Failure below.
Certain aminoglycosides have activity against Giardia ; most notably paromomycin and neomycin. It is commonly recommended for treatment of giardiasis, at least during the first trimester of pregnancy because of its perceived safety in that setting. Bacitracin with or without zinc and with or without neomycin, and neomycin were studied in 80 patients with about 20 in each group Asymptomatic Infection: Asymptomatic carriage of Giardia is very common in certain endemic areas, with recurrence of infection very soon after effective treatment In this setting, there do not appear to be long term adverse consequences of untreated infection Therefore, asymptomatic infections in highly endemic areas should usually not be treated.
Once a person or animal has been infected with Giardia , the parasite lives in the intestines and is passed in stool poop. Once outside the body, Giardia can sometimes survive for weeks or even months.
Giardia can be found in every region of the United States and around the world. You can get giardiasis if you swallow the Giardia parasite germ.
Giardia —or poop from people or animals infected with Giardia —can contaminate anything it touches. Giardia spreads very easily; even getting tiny amounts of poop in your mouth could make you sick.
Giardia infection giardiasis can cause a variety of intestinal symptoms , which include:. Symptoms of giardiasis generally begin by having 2 to 5 loose stools poop per day and progressively increasing fatigue. Other, less common symptoms include fever, itchy skin, hives, and swelling of the eyes and joints. Over time, giardiasis can also cause weight loss and keep the body from absorbing nutrients it needs, like fat, lactose, vitamin A, and vitamin B Some people with Giardia infections have no symptoms at all.
Symptoms generally last anywhere from 2 to 6 weeks. In people with weakened immune systems e. Healthcare providers can prescribe the appropriate antiparasitic medications to help reduce the amount of time symptoms last. Contact your healthcare provider if you think you may have giardiasis. Giardiasis infections usually last about six to eight weeks, but problems such as lactose intolerance can persist after the infection clears up. Yellow stool may be caused by changes in your diet.
It may also be a sign of an underlying medical condition. Here are seven possible causes. Amebiasis is a parasitic infection, common in the tropics and caused by contaminated water.
Symptoms can be severe and usually start weeks after…. Viruses, bacteria, fungi, and parasites can all cause skin infections. Infections can range from mild to severe. Learn what to do if you have a skin…. When parasites grow, reproduce, or invade organ systems it results in a parasitic infection in the host. Learn how to recognize and treat a parasitic…. A string test, or "entero-test," is used to detect the presence of parasites in the upper part of the small intestine.
Tropical sprue makes it difficult for your body to absorb certain nutrients. Read about signs and treatment. There are many dangerous signs of infections, and you might not even realize you have been bitten or infested until some time later. A toxoplasmosis test toxoplasma test determines if the Toxoplasma gondii parasite has infected you.
Learn about testing during pregnancy and more. Health Conditions Discover Plan Connect. Medically reviewed by Jill Seladi-Schulman, Ph. McArthur A. Morrison H. Nixon J. Passamaneck N. Kim U. Hinkle G. Crocker M. Holder M. Farr R. Reich C. Olsen G. Aley S. Gillin F. FEMS Microbiol. Reiner D. McCaffery J. Wiesehahn G. Jarroll E.
Lindmark D. Meyer E. Hallick L. Bernander R. Palm J. Cell Microbiol. Gault M. Douglas H. Das S. Wunderlich A. Sauch J. Science , — Lujan H. Mowatt M. Byrd L. Nash T. Byers T. Kim B. King L. Hugo E. Paget T. Macechko P. Touz M. Nores M. Slavin I. Piacenza L. Acosta D. Carmona C. Cotton D. Bowers B. Yee J. Stibbs H. Conrad J. Implications for secretory granule formation and protein assembly into the cyst wall. Coronel C. Hehl A. Marti M. Kohler P. Cell 11 , — Steimle P.
Bulik D. Karr C. Gerwig G. Kamerling J. Vliegenthart J. Erlandsen S. Knodler L. Silberman J. Davids B. Elmendorf H. Singer S. Nucleic Acids Res. Okada M. Akimaru H. Hou D. Takahashi T.
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