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Giardia lamblia or Giardia
intestinalis is a protozoan flagellate that is among the
most common disease-causing parasites in the United States and the
most frequently identified agent of waterborne diarrhea.1 Cases
are especially common in areas with inadequate water and sanitation
facilities. Humans are the major reservoir of infection, although
other mammals, such as dogs, cats, and beavers, may be colonized
and excrete cysts. Massive epidemics have occurred after the contamination
of reservoirs, lakes, and streams, especially when community water
supplies are not adequately filtered.
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Although giardiasis affects persons of all age groups, the populations
at highest risk are children ages 0 to 5 years and adults ages 31
to 40. In developing countries, Giardia infection
has been reported in almost 100% of children who were followed
prospectively from birth until age 2 years. In the United States
and other developed countries, Giardia is prevalent
in childcare centers and custodial institutions, among backpackers
and others spending time in wooded areas, and among travelers to
disease-endemic areas. Among children in daycare centers, Giardia cyst
carriage has been documented to be as high as 50%, and
many of these are asymptomatic carriers who can spread infection
to household contacts. Person-to-person spread via fecal-oral route
and ingestion of contaminated water are the most common modes of
transmission; infection through food is less common.
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Giardia cysts, present in the stool of infected
persons, are the infective form. After ingestion, they excyst in
the small intestine, yielding trophozoites that subsequently multiply.
The trophozoites remain limited to the mucosa, mucus, or lumen of
the intestine and are rarely, if ever, invasive (Fig.
349-1). Encystation normally occurs prior to expulsion in the
feces. Contamination of oneself and the environment with cysts is
common. The number of cysts excreted varies, but it may reach as
many as 10 million per gram. Infections are relatively frequent,
because as few as 10 cysts can infect 30% of inoculated
humans.
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The exact pathophysiology of the diarrhea is not known. The most severe
cases are characterized by malabsorption and lactose intolerance,
with varying degrees of inflammation and villous blunting. Host
factors are also determinants of disease outcome; only 40% of humans
infected with the same inoculum develop diarrhea. Patients with
hypogammaglobulinemia frequently suffer from particularly severe
cases of giardiasis. The observation that asymptomatic infections
are more common in persons previously infected with Giardia also
suggests partial immunity.
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Clinical Manifestations
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Clinical manifestations and duration of symptoms vary. Infections
range from asymptomatic cases to severe, life-threatening diarrhea
accompanied by malabsorption and dehydration. Infections may last
from a few days to years. In naturally occurring infections, symptoms
usually appear approximately 12 to 14 days after presumed exposure.
Passage of cysts usually begins 7 to 10 days after inoculation (range
5 to 21 days). Symptoms include watery, foul-smelling diarrhea,
which can be sudden in onset and accompanied by abdominal distension,
epigastric cramping, flatus, nausea, vomiting, anorexia, and fatigue.
Systemic symptoms such as fever and chills are uncommon. Blood and
mucus in the stools do not occur in giardiasis. Urticaria and arthritis
have been anecdotally associated. In its most florid manifestations,
giardiasis results in symptoms and signs associated with severe
small-intestinal malabsorption and weight loss. Although some patients
have severe symptoms at the onset of illness and seek medical care
shortly after becoming ill, the majority who seek medical attention complain
of remitting abdominal pain, nausea, or weight loss lasting weeks
to months.
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Giardiasis is confirmed by detecting the parasite or its antigens
in the stool or intestinal lining. Cysts are oval, 8 to 10 μm
long by 7 to 10 μm wide, and contain four nuclei. When
viewed dorsally, the trophozoite has a characteristic pear shape
and contains two similar nuclei. Trophozoites vary in size from
9 to 21 μm in length and 5 to 15 μm
in width. Other features include four paired flagella and a ventral sucking
disc with which the trophozoite attaches to the intestinal mucosa.
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Cysts are the most commonly detected form in the feces, and trophozoites
are almost entirely limited to liquid stools. Merthiolate-iodine-formalin
(MIF) concentration improves the detection of cysts. The number
of cysts excreted vary, and they may not be detected on any single
examination. If initial stool examination is negative, three stool
examinations spaced 2 days apart are recommended. Careful fecal
examination detects over 90% of infected individuals but
requires an experienced microscopist.
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Occasionally, cysts are not detected in the feces, and sampling
small-intestinal fluid by intubation or by the “string
test” is useful. For the string test, a capsule attached
to an absorbent string is swallowed, and trophozoites attach as the
capsule proceeds through the jejunum. After 4 hours, the string
is withdrawn and duodenal fluid on the string is examined for trophozoites. Esophagogastroduodenoscopy
with biopsy may be diagnostic.
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Commercially available assays for detecting Giardia antigen
in the stool may be useful when microscopy is negative.2 In
general, these tests are more sensitive than stool examination, with
similar specificity and with the added benefit of being much less
time-consuming than microscopy. Giardia antigens
may be detected by immunofluorescent ELISAs, nonenzymatic immunoassays
(some of which combine detection of Giardia and Cryptosporidium in
a single kit), and direct fluorescent antibody tests. These commercial
detection tests are similar in cost to microscopy but with better
reproducibility and more rapid return of results. Overall, antigen detection
tests have a sensitivity of 85% to 98% and a specificity
of 90% to 100% as compared to microscopy. Antibody
detection assays are rarely clinically useful, as the relationship
between serum antibody and clinical disease is unclear.
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Treatment and Prevention
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Because many people are asymptomatically infected, the decision to
treat should be based upon presence of symptoms such as diarrhea,
malabsorption, and failure to thrive. Asymptomatic cyst excreters
are generally not treated except in unusual circumstances—for
example, when attempting to prevent or control infections in a family with
high-risk individuals such as pregnant women or patients with hypogammaglobulinemia
or cystic fibrosis.
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Furazolidone (Furoxone) was the first anti-Giardia drug
to become available as a suspension in the United States, thus making
it particularly useful in infants and younger children. There are
mixed reports on the effectiveness of furazolidone, with cure rates
ranging from 77% to 92%. The dose for children
is 6 mg/kg per day, divided into four doses for 7 to 10
days.
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Metronidazole (Flagyl) is frequently prescribed for giardiasis
and is a highly effective drug for this indication (80–95% efficacy
after 7 days of treatment), but it remains unlicensed in the United
States for this purpose.3 Metronidazole is administered
in doses of 250 mg three times a day for 5 to 7 days for adults
and in doses of 5 mg/kg three times a day for 5 to 7 days
in children.4 Tinidazole (Tindamax) is FDA approved
for giardiasis and is considered by some to be first-line therapy,
because it is highly effective against Giardia with
single-dose treatment (90–95% efficacy when given
as a 2-gm dose to adults). Treatment failures with metronidazole
or tinidazole can be treated with another drug, with longer durations
of therapy and with increased amounts of drug when metronidazole
is used. Treatment failures with metronidazole are seen more commonly
in immunodeficient patients, including those with AIDS.
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Nitazoxanide (Alinia) is a broad-spectrum antiparasitic drug
active against a wide range of protozoa and intestinal helminthes,
as well as some bacteria.5 It is also FDA approved
for treating giardiasis in adults and children, and a liquid formulation
for pediatric patients is available. The drug interferes with anaerobic
energy metabolism by inhibiting some enzyme-dependent electron transfer
reactions. Clinical trials in children showed efficacy rates of 70% to
85%, similar to those seen with metronidazole therapy.
Nitazoxanide is usually administered for 3-day treatment courses,
making it an attractive alternative to other treatments that require
longer courses of therapy.
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Anthelminthic benzimidazole drugs such as albendazole and mebendazole
have recently been shown to have efficacy against Giardia similar
to that of metronidazole but with fewer adverse effects. Albendazole
was given for 5 days or longer in clinical trials for this indication,
so the efficacy of single-dose albendazole (as it is frequently
given for helminth infections) for giardiasis is not known.
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The most effective treatment is quinacrine hydrochloride (Atabrine),
although it is no longer available in the United States because
of concerns related to toxicity. Combined therapy with metronidazole
and quinacrine is effective in the rare patient who is refractory
to multiple courses of therapy. Paromomycin, a nonabsorbable aminoglycoside,
has limited efficacy (50–70%) but is recommended
for treating symptomatic giardiasis in pregnant women because of
its lack of systemic absorption.
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Food or drinks that are likely contaminated should be avoided. Hand-washing
and attention to personal hygiene are important preventative measures.
Potentially contaminated water should be boiled or filtered, because
chlorination, freezing, and disinfection by ultraviolet light are
not effective against Giardia.