infectious mononucleosus, amebiasis, and giardiasis

Epstein - Barr virus
EBV, a member of the herpesviruses, and Infectious mononucleosis is the best-known clinical syndrome caused by this virus. Originally described as glandular fever, it derives its name from the mononuclear lymphocytosis with atypical-appearing lymphocytes that accompany the illness. Other infections may cause infectious mononucleosis-like illnesses, like cytomegalovirus, Toxoplasma gondii, adenovirus, viral hepatitis, HIV, and possibly rubella virus.
EBV infects >95% of the world s population. It is transmitted in oral secretions by close contact such as kissing or exchange of saliva from child to child, such as occurs between children in out-of-home child care.
EBV is also found in the genital tract of women and may be spread by sexual contact.
Infection with EBV in developing countries usually occurs during infancy and early childhood. This syndrome may be seen at all ages but is rarely apparent in children <4 yr of age, when most EBV infections are asymptomatic.
Pathogenesis
After acquisition in the oral cavity, EBV initially infects oral epithelial cells; this may contribute to the symptoms of pharyngitis. After intracellular viral replication, virus spreads to contiguous structures such as the salivary glands, with eventual viremia and infection of B lymphocytes in the peripheral blood and the entire lymphoreticular system, including the liver and spleen. The atypical lymphocytes that are characteristic of infectious mononucleosis are CD8+ T lymphocytes, which exhibit both suppressor and cytotoxic functions that develop in response to the infected B lymphocytes. EBV, like the other herpesviruses, establishes lifelong latent infection after the primary illness. The latent virus is carried in oropharyngeal epithelial cells and systemic B lymphocytes. Reactivation is apparently asymptomatic and not recognized to be accompanied by distinctive clinical symptoms.
ONCOGENESIS
EBV was the first human virus to be associated with malignancy. Benign EBV-associated proliferations include oral hairy leukoplakia, primarily in adults with AIDS, and lymphoid interstitial pneumonitis, primarily in children with AIDS. Malignant EBV-associated proliferations include nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin disease, lymphoproliferative disorders, and leiomyosarcoma in immunodeficient states, including AIDS.
Clinical Manifestations
The incubation period of infectious mononucleosis in adolescents is 30–50 days. In children, it may be shorter. The majority of cases of primary EBV infection in infants and young children are clinically silent. In older patients, the onset of illness is usually insidious and vague. Patients may complain of malaise, fever, headache, sore throat, nausea, abdominal pain, and myalgia. This prodromal period may last 1–2 wk. The complaints of sore throat and fever gradually increase until patients seek medical care. Splenic enlargement may be rapid enough to cause left upper quadrant abdominal discomfort and tenderness, which may be the presenting complaint.
The physical examination is characterized by generalized lymphadenopathy (90% of cases), splenomegaly (50% of cases), and hepatomegaly (10% of cases).
Lymphadenopathy occurs most commonly in the anterior and posterior cervical nodes and the submandibular lymph nodes and less commonly in the axillary and inguinal lymph nodes. Epitrochlear lymphadenopathy is particularly suggestive of infectious mononucleosis. Symptomatic hepatitis or jaundice is uncommon.
The sore throat is often accompanied by moderate to severe pharyngitis with marked tonsillar enlargement, occasionally with exudates. Petechiae at the junction of the hard and soft palate are frequently seen. The pharyngitis resembles that caused by streptococcal infection. Other clinical findings may include rashes and edema of the eyelids. Rashes are usually maculopapular and have been reported in 3–15% of patients. Up to 80% of patients with infectious mononucleosis experience “ampicillin rash” if treated with ampicillin or amoxicillin. This vasculitic rash is probably immune-mediated and resolves without specific treatment.
Diagnosis
A presumptive diagnosis may be made by the presence of typical clinical symptoms with atypical lymphocytosis in the peripheral blood. The diagnosis is confirmed by serologic testing.
ROUTINE LABORATORY TESTS
In >90% of cases there is leukocytosis of 10,000–20,000 cells/mm3 , of which at least two thirds are lymphocytes; atypical lymphocytes usually account for 20–40% of the total number. Other syndromes associated with atypical lymphocytosis include acquired cytomegalovirus infection, toxoplasmosis, viral hepatitis, rubella, roseola, mumps, tuberculosis, typhoid, Mycoplasma infection, and malaria, as well as some drug reactions. Mild thrombocytopenia occurs in >50% of patients. Mild elevation of hepatic transaminases occurs in approximately 50% of uncomplicated cases but is usually asymptomatic without jaundice.
HETEROPHILE ANTIBODY TEST
The transient heterophile antibodies seen in infectious mononucleosis, also known as Paul-Bunnell antibodies, are IgM antibodies detected by the Paul-Bunnell-Davidsohn test for sheep red cell agglutination. The heterophile antibodies of infectious mononucleosis agglutinate sheep red cells. The sheep red cell agglutination test is likely to be positive for several months after infectious mononucleosis. It detects heterophile antibody in 90% of cases of EBV-associated infectious mononucleosis in older children and adults but in only up to 50% of cases in children <4 yr of age because they typically develop a lower titer.
From 5–10% of cases of infectious mononucleosis are not caused by EBV and are not uniformly associated with a heterophile antibody response. The false-positive rate is <10%, usually resulting from erroneous interpretation. If the heterophile test is negative and an EBV infection is suspected, EBV-specific antibody testing is indicated.
SPECIFIC EBV ANTIBODIES
EBV-specific antibody testing is useful to confirm acute EBV infection, especially in heterophile-negative cases, or to confirm past infection and determine susceptibility to future infection. Several distinct EBV antigen systems have been characterized for diagnostic purposes. The EBNA (EB nuclear antigen), EA (Early antigen), and VCA (viral capsid antigen) antigen systems are most useful for diagnostic purposes. The acute phase of infectious mononucleosis is characterized by rapid IgM and IgG antibody responses to VCA in all cases and an IgG response to EA in most cases. The IgM response to VCA is transient but can be detected for at least 4 wk. The IgG response to VCA usually peaks late in the acute phase, declines slightly over the next several weeks to months, and then persists at a relatively stable level for life.
Anti-EA antibodies are usually detectable for several months but may persist or be detected intermittently at low levels for many years. Anti-EBNA antibodies are the last to develop in infectious mononucleosis and gradually appear 3–4 mo after the onset of illness and remain at low levels for life. Absence of anti-EBNA when other antibodies are present implies recent infection, whereas the presence of anti-EBNA implies infection occurring more than 3–4 mo previously. The detection of IgM antibody to VCA is the most valuable and specific serologic test for the diagnosis of acute EBV infection and is generally sufficient to confirm the diagnosis.
DIFFERENTIAL DIAGNOSIS
Infectious mononucleosis-like illnesses may be caused by primary infection with cytomegalovirus, T. gondii, adenovirus, viral hepatitis, HIV, or possibly rubella virus, Group A ?-hemolytic streptococci, and
Leukemia.

Treatment
There is no specific treatment for infectious mononucleosis. Rest and symptomatic therapy are the mainstays of management. Bed rest is necessary only when the patient has debilitating fatigue. Because blunt abdominal trauma may predispose patients to splenic rupture, it is customary and prudent to advise against participation in contact sports and strenuous athletic activities during the first 2–3 wk of illness or while splenomegaly is present.
Short courses of corticosteroids (less than 2 wk) may be helpful for complications of infectious mononucleosis, but this use has not been evaluated critically. Some appropriate indications include incipient airway obstruction, thrombocytopenia with hemorrhaging, autoimmune hemolytic anemia, and seizures and meningitis. A recommended dosage is prednisone, 1mg/kg/ 24hr (maximum: 60mg/24hr) or equivalent, for 7 days and tapered over another 7 days. Corticosteroids should not be used in uncomplicated cases of infectious mononucleosis.
Complications
The most feared complication is subcapsular splenic hemorrhage or splenic rupture, which occurs most frequently during the 2nd week of the disease at a rate of <0.5% of cases in adults; the rate in children is unknown but is probably much lower. Rupture is commonly related to trauma, which often may be mild, and is rarely fatal. Swelling of the tonsils and oropharyngeal lymphoid tissue may be substantial and cause airway obstruction that is manifest by stridor and interference with breathing. Airway impairment with progressive symptoms occurs in <5% of cases and is one of the most common indications for hospitalization with infectious mononucleosis. It may be treated by administration of head-of-bed elevation, intravenous hydration, humidified air, and systemic corticosteroids. Respiratory distress with incipient or actual airway occlusion should be managed by tonsilloadenoidectomy followed by endotracheal intubation for 12–24hr in an intensive care setting.
Many uncommon and unusual neurologic conditions have been reported to be associated with EBV infectious mononucleosis. Headache is present in about half of cases, with severe neurologic manifestations, such as seizures and ataxia, in 1–5% of cases. Perceptual distortions of sizes, shapes, and spatial relationships, known as the Alice in Wonderland syndrome (metamorphopsia), may be a presenting symptom. There may be meningitis with nuchal rigidity and mononuclear cells in the cerebrospinal fluid, facial nerve palsy, transverse myelitis, and encephalitis. Guillain-Barré syndrome or Reye syndrome may follow acute illness.
Hemolytic anemia, often with a positive Coombs test and with cold agglutinins specific for red cell antigen i, occurs in 3% of cases. The onset is typically in the first 2 wk of illness and lasts for <1 mo. Aplastic anemia is a rare complication that usually presents 3–4 wk after the onset of illness, usually with recovery in 4–8 days but some cases do require bone marrow transplantation. Mild thrombocytopenia and neutropenia are
common, but severe thrombocytopenia (<20,000 platelets/?L) or severe neutropenia (<1,000 neutrophils/?L) are rare. Myocarditis or interstitial pneumonia may occur, both resolving in 3–4 wk. Other rare complications include pancreatitis, parotitis, and orchitis.
Amebiasis
Human infection with Entamoeba is prevalent worldwide; endemic foci are common especially in areas with low socioeconomic and sanitary standards. There are two morphologically identical but genetically distinct species of Entamoeba that commonly infect humans. Entamoeba dispar, the more prevalent species, is associated only with an asymptomatic carrier state. Entamoeba histolytica, the pathogenic species, can become invasive, causing symptomatic disease.
Infection is established by ingestion of parasite cysts, which are resistant to environmental conditions such as low temperature and the concentrations of chlorine commonly used in water purification; the parasite can be killed by heating to 55°C. On ingestion, the cyst, which is resistant to gastric acidity and digestive enzymes, excysts in the small intestine to form eight trophozoites. These are large, actively motile organisms that colonize the lumen of the large intestine and may invade its mucosal lining under conditions that are currently unknown. Once attached to the colonic mucosa, amebas release a cysteine-rich proteinase that allows for penetration through the epithelial layer. The organisms multiply and spread laterally underneath the intestinal epithelium to produce characteristic flask-shaped ulcers. These lesions are commonly seen in the cecum, transverse colon, and sigmoid colon. Amebae may produce similar lytic lesions if they reach the liver; these lesions are commonly called abscesses, although they contain no granulocytes.
Epidemiology
The regional prevalence of amebic infections worldwide varies from 5–81%, with the highest frequency in the tropics. Humans are the major reservoir. Food or drink contaminated with Entamoeba cysts and direct fecal-oral contacts are the most common means of infection. Food handlers carrying amebic cysts may, therefore, play a role in spreading the infection.

Clinical Manifestations
Clinical presentations range from asymptomatic cyst passage to amebic colitis, amebic dysentery, ameboma, and extraintestinal disease. To date, E. dispar has not been associated with symptomatic disease. E. histolytica infection is asymptomatic in 90% of persons, but it has the potential to become invasive and thus should be treated. Severe disease is more common in young children, pregnant women, malnourished individuals, and person using corticosteroids.
Extraintestinal disease usually involves only the liver, but rare extraintestinal manifestations include amebic brain abscess, pleuropulmonary disease, and ulcerative skin lesions.
INTESTINAL AMEBIASIS
Intestinal amebiasis may occur within 2 wk of infection or be delayed for months. Amebic colitis affects all age groups, but its incidence is strikingly high in children 1–5 yr of age. The onset is usually gradual with colicky abdominal pains and frequent bowel movements (6–8/day). Diarrhea is frequently associated with tenesmus. Stools are blood stained and contain a fair amount of mucus with few leukocytes. Generalized constitutional symptoms and signs are characteristically absent, with fever documented in only one third of patients. Occasionally, amebic dysentery is associated with sudden onset of fever, chills, and severe diarrhea, which may result in dehydration and electrolyte disturbances. In a few patients complications such as ameboma, toxic megacolon, extraintestinal extension, or local perforation and peritonitis may occur.
Uncommonly, a chronic form of amebic colitis develops, which can mimic inflammatory bowel disease with bouts of abdominal pain and bloody diarrhea, often recurring over several years. An ameboma is a nodular focus of proliferative inflammation sometimes developing in chronic amebiasis, usually in the wall of the colon. Chronic amebiasis should be excluded before initiating corticosteroid treatment for inflammatory bowel disease.

HEPATIC AMEBIASIS
Hepatic amebiasis is a very serious manifestation of disseminated infection. Although diffuse liver enlargement has been associated with intestinal amebiasis, liver abscess occurs in less than 1% of infected individuals and may appear in patients with no clear history of intestinal disease. In children, fever is the hallmark of amebic liver abscess and is frequently associated with abdominal pain, distention, and enlargement and tenderness of the liver. Changes at the base of the right lung, such as elevation of the diaphragm and atelectasis or effusion, may also occur.
Laboratory examination findings are a slight leukocytosis, moderate anemia, high erythrocyte sedimentation rate, and nonspecific elevations of hepatic enzyme (particularly alkaline phosphatase) level. Stool examination for amebae yields negative results in more than 50% of patients with documented amebic liver abscess. In most cases, CT and MRI scans, can localize and delineate the size of the abscess cavity. Most patients have a single cavity in the right hepatic lobe. Amebic liver abscess may be associated with rupture into the peritoneum or thorax or through the skin when diagnosis and therapy are delayed.
Diagnosis
Diagnosis is based on detecting the organisms in stool samples, sigmoidoscopically obtained smears, tissue biopsy samples, or, rarely, aspirates of a liver abscess.
Examination of three fresh stool samples by experienced laboratory personnel has a sensitivity of 90% for detecting Entamoeba. Fresh stool samples should be examined within 30min of passage and screened for motile trophozoites containing erythrocytes. Endoscopy and biopsies of suspicious areas should be performed when stool sample results are negative and the index of suspicion for amebiasis remains high. Patients with invasive amebic colitis have positive test results for fecal occult blood.
Various serum antiamebic antibody tests are available. Serologic results are positive in 70-80% of patients with invasive disease (colitis or liver abscess) at presentation, and in >90% of patients after 7 days of disease symptoms. The most sensitive serologic test, indirect hemagglutination, yields a positive result years after invasive infection. Therefore, many uninfected adults and children in highly endemic areas demonstrate antibodies to E. histolytica. Detection of E. histolytica antigens in serum is perhaps the ideal test because it is sensitive and specific, can distinguish E. dispar from E. histolytica, and can distinguish current from past infection. However, serum antigen detection tests are not yet routinely available.
The differential diagnosis for amebic colitis includes colitis due to bacterial (Shigella, Salmonella, enteropathogenic Escherichia coli, Campylobacter, Yersinia, Clostridium difficile) and viral (cytomegalovirus) pathogens, as well as noninfectious causes such as inflammatory bowel disease. Pyogenic liver abscess due to bacterial infection, hepatoma, and echinococcal cysts are in the differential for amebic liver abscess. However, echinococcal cysts are rarely associated with systemic symptoms such as fever.
COMPLICATIONS
Complications of amebic colitis include necrotizing colitis, ameboma, toxic megacolon, extraintestinal extension, or local perforation and peritonitis. Uncommonly, a chronic form of amebic colitis develops. Amebic liver abscess may be associated with rupture into the peritoneum, pleural cavity, skin, or, rarely, pericardium when diagnosis and therapy are delayed. Cases of amebic abscesses in extrahepatic sites, including the lung and brain, have been reported.
Treatment
Two types of drugs are used to treat infection with E. histolytica. The luminal amebicides, such as iodoquinol, paromomycin, and diloxanide furoate, are primarily effective in the gut lumen. Metronidazole or other nitroimidazoles, chloroquine, and dehydroemetine are effective in the treatment of invasive amebiasis. All individuals with E. histolytica trophozoites or cysts in their stools, whether symptomatic or not, should be treated.
Invasive amebiasis of the intestine, liver, or other organs requires the use of metronidazole (30–50mg/kg/24hr divided tid PO for 10 days; maximum: 500–750mg/dose), a tissue amebicidal drug. Two related nitroimidazoles, tinidazole and ornidazole, are available and have been used outside the United States. Adverse effects of metronidazole include nausea, abdominal discomfort, and metallic taste; these are uncommon and disappear after completion of therapy.
For fulminant cases, some experts suggest adding dehydroemetine (1mg/kg/24hr subcutaneously or IM, never IV). Chloroquine, which concentrates in the liver, may be useful in the treatment of amebic hepatic abscess. Aspiration of large lesions or left lobe abscesses may be necessary if rupture is imminent or if the patient shows a poor clinical response 4–6 days after administration of amebicidal drugs.
Stool examination should be repeated every 2 wk until the result is negative after completion of antiamebic therapy to confirm cure.

Prognosis
Most infections evolve to either an asymptomatic carrier state or eradication. Death occurs in about 5% of persons having extraintestinal infection.

Giardia lamblia
Giardia lamblia (also referred to as G. intestinalis and G. duodenalis) is a flagellated protozoan that infects the duodenum and small intestine. Infection is more prevalent in children than in adults. Giardia organisms are endemic in areas of the world with poor levels of sanitation. Giardia is a particularly significant pathogen in people with malnutrition, certain immunodeficiencies, and cystic fibrosis.
Giardia infects humans after ingestion of as few as 10–100 cysts. Ingested cysts each produce two trophozoites in the duodenum. After excystation, trophozoites colonize the lumen of the duodenum and proximal jejunum, where they attach to the brush border of the intestinal epithelial cells and multiply by binary fission. As detached trophozoites pass down the intestinal tract, they encyst to form oval cysts. Cysts are passed in stools of infected individuals and may remain viable in water for as long as 2 mo. Their viability often is not affected by the usual concentrations of chlorine used to purify water for drinking.
Epidemiology
The age-specific prevalence of giardiasis is high during childhood and begins to decline after adolescence. Asymptomatic carriage may persist for several months. The major reservoir and vehicle for spread of Giardia appears to be water contaminated with Giardia cysts, but foodborne transmission occurs. Giardia cysts are relatively resistant to chlorination and to ultraviolet light irradiation, boiling is effective for inactivating cysts.
Humoral immunodeficiencies including common variable hypogammaglobulinemia and X-linked agammaglobulinemia predispose humans to chronic symptomatic Giardia infection, suggesting the importance of humoral immunity in controlling giardiasis. There is a higher incidence of Giardia infection in patients with cystic fibrosis, probably owing to local factors such as the increased amount of mucus, which may protect the organism against host factors in the duodenum. Human milk contains glycoconjugates and secretory IgA antibodies that may provide protection to nursing infants.
Clinical Manifestations
The incubation period of Giardia infection usually is 1–2 wk but may be longer. Children with G. lamblia may experience asymptomatic excretion of the organism, acute infectious diarrhea, or chronic diarrhea with persistent gastrointestinal tract signs and symptoms, including failure to thrive. Most infections in both children and adults are asymptomatic.
Symptomatic infections occur more frequently in children than in adults. Most symptomatic patients usually have a limited period of acute diarrheal disease with or without low-grade fever, nausea, and anorexia; in a small proportion an intermittent or more protracted course characterized by diarrhea, abdominal distention and cramps, bloating, malaise, flatulence, nausea, anorexia, and weight loss develops. Initially, stools may be profuse and watery and later becomes greasy and foul smelling and may float. Stools do not contain blood, mucus, or fecal leukocytes. Varying degrees of malabsorption may occur. Abnormal stool patterns may alternate with periods of constipation and normal bowel movements. Malabsorption of sugars, fats, and fat-soluble vitamins has been well documented and may be responsible for substantial weight loss.


Diagnosis
Giardiasis should be considered in young children in child care or in any person who has had contact with an index case or a history of recent travel to an endemic area who has persistent diarrhea, intermittent diarrhea and constipation, malabsorption, crampy abdominal pain and bloating, or failure to thrive or weight loss.
A definitive diagnosis of giardiasis is established by documentation of trophozoites, cysts, or Giardia antigens in stool specimens or duodenal fluid. Several types of specimens from the gastrointestinal tract can be used to diagnose Giardia infection.
For both trophozoites and cysts of Giardia organisms, identification can be made on direct smears of stool specimens. Stool specimens should be examined within 1hr of passage. Trophozoites may be present in unformed stools as a result of rapid bowel transit; they are not stable outside the gastrointestinal tract.
Cysts are stable outside the gastrointestinal tract and are the infectious form. In patients in whom the diagnosis is suspected but in whom examination of stool specimens for Giardia yields a negative result, aspiration or biopsy of the duodenum or upper jejunum should be performed. The biopsy can be used to make touch preparations and tissue sections for identification of Giardia and other enteric pathogens, as well as to visualize changes in histologic features.
Appropriately conducted direct examination of stool will establish the diagnosis in up to 70% of patients by a single examination, 85% by examination of a second stool specimen, and more than 90% by examination of three specimens. Comparison of stool examination results with small bowel aspiration results in patients with diarrhea revealed that parasites were detected in 50% of stools of patients in whom a small bowel focus of infection was documented by aspiration. Efforts to improve diagnostic testing include the use of polyclonal antisera or monoclonal antibodies against Giardia organism–specific antigens in EIA or immunofluorescent assays. Polymerase chain reaction and gene probe–based detection systems specific for Giardia have been used in environmental monitoring.
Radiographic contrast studies of the small intestine may show nonspecific findings such as irregular thickening of the mucosal folds. Blood cell counts usually are normal. Giardiasis is not associated with eosinophilia.
Treatment
Children with acute diarrhea in whom Giardia organisms are identified should receive therapy. In addition, children who manifest failure to thrive or exhibit malabsorption or gastrointestinal tract symptoms such as chronic diarrhea should be treated.
Asymptomatic excreters generally are not treated except in specific instances such as in outbreak control, for prevention of household transmission by toddlers to pregnant women and patients with hypogammaglobulinemia or cystic fibrosis.
Metronidazole is the treatment most often prescribed in the United States for adults. Furazolidone is less effective than metronidazole but is often prescribed in children because it is available in liquid form. Furazolidone is the only drug approved by the U.S. Food and Drug Administration for treatment of giardiasis. Quinacrine is effective and inexpensive but is not available from any U.S. manufacturer. Albendazole appears to be as effective as metronidazole with fewer adverse effects among children 2–12 yr of age and is effective against many helminths, making it useful for treatment when multiple intestinal parasites are identified or suspected.
Paromomycin, a nonabsorbable aminoglycoside, is less effective than other agents but is recommended for treatment of pregnant women with giardiasis because of potential teratogenic effects of other agents. A combination of metronidazole and quinacrine has been used to treat refractory cases.

Prognosis
Several studies have demonstrated that variability in antimicrobial susceptibility exists among strains of Giardia, and in some instances resistant strains have been demonstrated. Combined therapy may benefit patients in whom infection persists after single-drug therapy, assuming reinfection has not occurred and the medication was taken as prescribed.
Giardia lamblia
Giardia lamblia (also referred to as G. intestinalis and G. duodenalis) is a flagellated protozoan that infects the duodenum and small intestine. Infection is more prevalent in children than in adults. Giardia organisms are endemic in areas of the world with poor levels of sanitation. Giardia is a particularly significant pathogen in people with malnutrition, certain immunodeficiencies, and cystic fibrosis.
Giardia infects humans after ingestion of as few as 10–100 cysts. Ingested cysts each produce two trophozoites in the duodenum. After excystation, trophozoites colonize the lumen of the duodenum and proximal jejunum, where they attach to the brush border of the intestinal epithelial cells and multiply by binary fission. As detached trophozoites pass down the intestinal tract, they encyst to form oval cysts. Cysts are passed in stools of infected individuals and may remain viable in water for as long as 2 mo. Their viability often is not affected by the usual concentrations of chlorine used to purify water for drinking.
Epidemiology
The age-specific prevalence of giardiasis is high during childhood and begins to decline after adolescence. Asymptomatic carriage may persist for several months. The major reservoir and vehicle for spread of Giardia appears to be water contaminated with Giardia cysts, but foodborne transmission occurs. Giardia cysts are relatively resistant to chlorination and to ultraviolet light irradiation, boiling is effective for inactivating cysts.
Humoral immunodeficiencies including common variable hypogammaglobulinemia and X-linked agammaglobulinemia predispose humans to chronic symptomatic Giardia infection, suggesting the importance of humoral immunity in controlling giardiasis. There is a higher incidence of Giardia infection in patients with cystic fibrosis, probably owing to local factors such as the increased amount of mucus, which may protect the organism against host factors in the duodenum. Human milk contains glycoconjugates and secretory IgA antibodies that may provide protection to nursing infants.
Clinical Manifestations
The incubation period of Giardia infection usually is 1–2 wk but may be longer. Children with G. lamblia may experience asymptomatic excretion of the organism, acute infectious diarrhea, or chronic diarrhea with persistent gastrointestinal tract signs and symptoms, including failure to thrive. Most infections in both children and adults are asymptomatic.
Symptomatic infections occur more frequently in children than in adults. Most symptomatic patients usually have a limited period of acute diarrheal disease with or without low-grade fever, nausea, and anorexia; in a small proportion an intermittent or more protracted course characterized by diarrhea, abdominal distention and cramps, bloating, malaise, flatulence, nausea, anorexia, and weight loss develops. Initially, stools may be profuse and watery and later becomes greasy and foul smelling and may float. Stools do not contain blood, mucus, or fecal leukocytes. Varying degrees of malabsorption may occur. Abnormal stool patterns may alternate with periods of constipation and normal bowel movements. Malabsorption of sugars, fats, and fat-soluble vitamins has been well documented and may be responsible for substantial weight loss.


Diagnosis
Giardiasis should be considered in young children in child care or in any person who has had contact with an index case or a history of recent travel to an endemic area who has persistent diarrhea, intermittent diarrhea and constipation, malabsorption, crampy abdominal pain and bloating, or failure to thrive or weight loss.
A definitive diagnosis of giardiasis is established by documentation of trophozoites, cysts, or Giardia antigens in stool specimens or duodenal fluid. Several types of specimens from the gastrointestinal tract can be used to diagnose Giardia infection.
For both trophozoites and cysts of Giardia organisms, identification can be made on direct smears of stool specimens. Stool specimens should be examined within 1hr of passage. Trophozoites may be present in unformed stools as a result of rapid bowel transit; they are not stable outside the gastrointestinal tract.
Cysts are stable outside the gastrointestinal tract and are the infectious form. In patients in whom the diagnosis is suspected but in whom examination of stool specimens for Giardia yields a negative result, aspiration or biopsy of the duodenum or upper jejunum should be performed. The biopsy can be used to make touch preparations and tissue sections for identification of Giardia and other enteric pathogens, as well as to visualize changes in histologic features.
Appropriately conducted direct examination of stool will establish the diagnosis in up to 70% of patients by a single examination, 85% by examination of a second stool specimen, and more than 90% by examination of three specimens. Comparison of stool examination results with small bowel aspiration results in patients with diarrhea revealed that parasites were detected in 50% of stools of patients in whom a small bowel focus of infection was documented by aspiration. Efforts to improve diagnostic testing include the use of polyclonal antisera or monoclonal antibodies against Giardia organism–specific antigens in EIA or immunofluorescent assays. Polymerase chain reaction and gene probe–based detection systems specific for Giardia have been used in environmental monitoring.
Radiographic contrast studies of the small intestine may show nonspecific findings such as irregular thickening of the mucosal folds. Blood cell counts usually are normal. Giardiasis is not associated with eosinophilia.
Treatment
Children with acute diarrhea in whom Giardia organisms are identified should receive therapy. In addition, children who manifest failure to thrive or exhibit malabsorption or gastrointestinal tract symptoms such as chronic diarrhea should be treated.
Asymptomatic excreters generally are not treated except in specific instances such as in outbreak control, for prevention of household transmission by toddlers to pregnant women and patients with hypogammaglobulinemia or cystic fibrosis.
Metronidazole is the treatment most often prescribed in the United States for adults. Furazolidone is less effective than metronidazole but is often prescribed in children because it is available in liquid form. Furazolidone is the only drug approved by the U.S. Food and Drug Administration for treatment of giardiasis. Quinacrine is effective and inexpensive but is not available from any U.S. manufacturer. Albendazole appears to be as effective as metronidazole with fewer adverse effects among children 2–12 yr of age and is effective against many helminths, making it useful for treatment when multiple intestinal parasites are identified or suspected.
Paromomycin, a nonabsorbable aminoglycoside, is less effective than other agents but is recommended for treatment of pregnant women with giardiasis because of potential teratogenic effects of other agents. A combination of metronidazole and quinacrine has been used to treat refractory cases.

Prognosis
Several studies have demonstrated that variability in antimicrobial susceptibility exists among strains of Giardia, and in some instances resistant strains have been demonstrated. Combined therapy may benefit patients in whom infection persists after single-drug therapy, assuming reinfection has not occurred and the medication was taken as prescribed.