AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Schistosomiasis (also known as bilharzia, bilharziasis, bilharziosis or snail fever) is a human disease syndrome caused by infection from one of several species of parasitic trematodes of the genus Schistosoma. Schistosomiasis is a major source of morbidity and mortality for developing countries in Africa, South America, the Caribbean, the Middle East, and Asia. Tourism to and immigration from endemic areas can result in schistosomiasis cases presenting anywhere in the developed world. Acute schistosomiasis among travelers may be increasing, and rates of emigration from endemic areas are increasing. In the complete absence of routine pre-symptomatic screening of these groups in developed countries, it is increasingly likely that patients with acute or chronic schistosomiasis will present to EDs with a variety of complaints.

Most human schistosomiasis is caused by Schistosoma haematobium, Schistosoma mansoni, or Schistosoma japonicum. Less prevalent species such as Schistosoma mekongi and Schistosoma intercalatum may also cause systemic human disease. Less importantly, other schistosomes with avian or mammalian primary hosts can cause severe dermatitis in humans (eg, swimmer's itch secondary to Trichobilharzia ocellata).

The geographic distribution and pathophysiology of schistosomiasis reflect the unique life cycle of these parasites. Schistosomes infect susceptible freshwater snails in endemic areas, usually with specific species of schistosomes infecting specific species of snails. The infected snails release cercariae 4-6 weeks after infection. The cercariae are fork-tailed free-swimming larvae approximately 1 mm in length. They can survive in freshwater up to 72 hours, during which time they must attach to human skin or to that of another susceptible host mammal or die.

Successful cercariae attach to human hosts utilizing oral and ventral suckers. They then migrate through intact skin to dermal veins and, over the next several days, to the pulmonary vasculature. During this migration, the cercariae metamorphose, shedding tails and outer glycocalyces while developing double-lipid-bilayer teguments that are highly resistant to host immune responses.

The organisms, now called schistosomula, incorporate host proteins, including major histocompatibility complexes (MHCs) and blood group antigens, in their integuments. Their metabolism shifts to glycolysis. The worms then migrate through the pulmonary capillaries to the systemic circulation, which carries them to the portal veins where they mature. Within the portal vasculature, male and female adults pair off, with the thin female entering and remaining in the gynecophoric canal of the stockier 8-mm male worm. Together they migrate along the endothelium, against portal blood flow, to the mesenteric (S mansoni, S japonicum) or vesicular (S haematobium) veins where they begin to produce eggs.

The eggs, which are highly antigenic and can induce an intense granulomatous response, migrate through the bowel or bladder wall to be shed via feces or urine. During this time (approximately 10 d) they begin to mature into miracidia. Eggs that are not shed successfully may remain in the tissues or be swept back to the portal circulation (from the mesenteric vessels) or to the pulmonary circulation (from the vesicular vessels via the inferior vena cava [IVC]).

The free-swimming miracidia that are shed into freshwater survive 1-3 weeks, during which time they must infect a susceptible snail to complete the life cycle. Within the infected snail, 2 generations of sporocysts multiply, mature into free-swimming cercariae, and exit the snail to seek a human host and begin a new cycle.

Pathophysiology

Acute schistosomiasis

Acute schistosomiasis (Katayama fever) is a systemic, serum sicknesslike illness that develops after several weeks in some, but not most, individuals with new schistosomal infections. It may correspond to the first cycle of egg deposition and is associated with marked peripheral eosinophilia and circulating immune complexes. It is most common with S japonicum and S mansoni infections and is most likely to occur in heavily infected individuals after primary infection. Symptoms usually resolve over several weeks, but the syndrome can be fatal. Early treatment with cidal drugs may exacerbate this syndrome and necessitate concomitant glucocorticoid therapy. Tourists and travelers are most likely to present to EDs in this country with this syndrome; a history of contact with freshwater such as swimming, boating, rafting, or water skiing should be obtained.

Mild maculopapular skin lesions may develop in acute infection within hours after exposure to cercariae. Significant dermatitis is rare with the major human schistosomal pathogens, probably because the invading and developing cercariae are minimally immunogenic. However, abortive human infection with schistosomal species that rely on other primary hosts may cause marked dermatitis or swimmer's itch. This self-limited process may recur more intensely with subsequent exposures to the same species.

Chronic schistosomiasis

The pathology of chronic schistosomiasis, which is far more common than the acute form of the infection, results from egg-induced immune response, granuloma formation, and associated fibrotic changes. Although cercarial and adult worms are minimally immunogenic, schistosomal eggs are highly immunogenic and induce vigorous circulating and local immune responses. (Eggs may require an intense immune response to aid their migration through the body.)

Egg retention and granuloma formation in the bowel wall (usually S mansoni or S japonicum) may cause bloody diarrhea, cramping, and, eventually, inflammatory colonic polyposis. Patients with heavy bowel wall involvement have an increased rate of recurrent salmonellal infection, generally with positive blood cultures and negative stool cultures.

Unshed eggs, which are swept back to the portal circulation, lodge there and induce granulomatous reactions in the portal tracts. Heavy infestations are more likely to produce hepatic disease. Eventually, severe periportal fibrosis in a characteristic pipestem pattern ("Symmer's pipestem fibrosis") may occur. Although hepatocellular function is spared, periportal fibrosis can lead to portal hypertension with the usual potential sequelae, including splenomegaly, ascites, esophageal variceal bleeding, and development of portosystemic collaterals. Through these collaterals (or directly from the IVC in the case of bladder wall schistosomiasis), eggs can reach the pulmonary circulation. The resulting pulmonary granulomatosis and fibrosis can lead to pulmonary hypertension and frank cor pulmonale with a high mortality rate. Co-infection with hepatitis B or hepatitis C can accelerate hepatic dysfunction and raise the risk for hepatocellular carcinoma beyond that seen with hepatitis alone. In addition, gallbladder cancer may be associated with schistosomal infection.

Egg retention and granuloma formation in the urinary tract (S haematobium) can lead to hematuria, dysuria, bladder polyps and ulcers, and even obstructive uropathies. S haematobium infection is also associated with an increased rate of bladder cancer, usually squamous cell rather than transitional cell.

Ectopic egg deposition can lead to additional clinical syndromes including involvement of skin, lung, brain, muscle, adrenal glands, genitalia, and eyes. Central nervous system involvement can result in transverse myelitis (best described for S haematobium and S mansoni) and/or cerebral disease (most common with S japonicum infection).

Frequency

United States

Acute and chronic schistosomiasis infections are not common in the United States. Although it is estimated that 400,000 infected persons have immigrated to this country, neither susceptible snail species nor chronically infected human reservoirs sufficient to infest freshwater exist. However, pathogenic schistosomes can survive and replicate in human hosts for years and even decades. Therefore, persons who have traveled or immigrated may present to EDs with active cases of acute or chronic schistosomiasis and/or the associated end-organ complications described.

International

Globally, schistosomiasis is a major source of morbidity and mortality. The unique schistosomal life cycle limits endemic areas to tropical and subtropical zones, but these areas exist around the world. Geographic spread continues because of water resource engineering issues in developing countries and the migration of infected populations. At least 200 million people in at least 74 countries have active schistosomal infection.¹ Of these, approximately 120 million people have symptoms, and 20 million are severely ill. Disease prevalence is heterogeneous in vulnerable locales and tends to be worse in areas with poor sanitation, increased freshwater irrigation usage, and heavy schistosomal infestation of human and/or snail populations.

Over the past decade, targeted interventions combining snail control, improved water supply quality, and treatment of infected persons, particularly children, have shown success in diverse endemic areas including China, Brazil, Egypt, and, most recently, some areas of sub-Saharan Africa. Nevertheless, the human cost of schistosomal infections remains high, and schistosomiasis contributes to comorbidity with other infections such as hepatitis, human immunodeficiency virus (HIV), and malaria in endemic regions.
 
Schistosomal species vary with geographic region: S mansoni and S haematobium infections predominate in sub-Saharan Africa. S mansoni is endemic in parts of South America and the Caribbean. S japonicum is common in China, Indonesia, and the Philippines. Although freshwater lakes and streams are usually identified as the source, man-made reservoirs and irrigation systems are increasingly implicated in some countries.

Mortality/Morbidity

• Acute schistosomiasis is associated with a mortality rate of up to 25% in some series. Although most individuals with chronic schistosomiasis have few or no symptoms, significant morbidity can develop.
• Complaints are difficult to quantitate because of the geographic distribution of this infection in underdeveloped nations and the frequency of comorbid conditions such as hepatitis. Hepatosplenic disease with portal hypertension is the most common long-term serious outcome, followed by cardiopulmonary involvement, obstructive nephropathy, bacteremia, and malignancy. Female genital infection can contribute to pregnancy complications including reports of related ectopic pregnancy.
• End-stage hepatosplenic disease with variceal bleeding, pulmonary hypertension with cor pulmonale, and central nervous system disease are associated with high mortality rates. Carcinoma of the urinary tract, liver, and gallbladder may cause death. Although effective antihelminthic treatment exists, it may not reverse fibrosis and may not be readily available in endemic areas.

Race

• The frequency of infection among individuals of specific races is based on the geographic distribution of endemic schistosomiasis in large tropical and subtropical regions of Africa, Asia, the Middle East, and the Caribbean. However, all humans appear equally susceptible if exposed to infested freshwater.
• The frequency of some complications appears to vary geographically during infection with the same worm species (eg, ascites is more common in the Middle East than in Brazil).

Sex

• In some endemic areas, rates of symptomatic infection vary between the sexes. This appears to reflect lifestyle differences between men and women regarding the likelihood of exposure to contaminated freshwater by activities such as bathing, working on irrigation equipment, or drinking from streams or irrigation ditches.
• S haematobium causes genital lesions in 30% of women who are infected. Vulval lesions may increase the risk of HIV transmission.

Age

The prevalence and severity of schistosomal infections vary with age.

• Children and adolescents are infected most often and are infested most heavily. As noted above, infection rates and severity may vary with gender-specific activity at all ages.
• Infections peak in individuals aged 10-19 years. In some areas, the prevalence in this group may approach 100%.
• In persons older than 19 years, the prevalence of active infection and egg counts slowly declines in populations living in endemic areas. (End-stage complications may persist or worsen.) This decline in active infection may reflect that individuals have an increasing host immune response or a decreasing exposure to contaminated water as they age. Reinfection, particularly after high exposure, is possible.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients with acute schistosomiasis (Katayama fever) present several weeks after contact with infested water. Obtaining a careful travel history, including drinking water sources and recreational activities, is important. Symptoms are likely secondary to immune complex formation following egg deposition in tissues; the illness resembles serum sickness.  
• • Fever
  • Headache
  • Malaise
  • Arthralgias/myalgias
  • Cough
  • Bloody diarrhea
  • Right upper quadrant (RUQ) pain
  • Rash - Urticarial and/or papular (Rash is the only symptom in patients with cercarial dermatitis due to exposure to less pathogenic species.)
• Patients with symptomatic chronic schistosomiasis may present months to years after primary exposure. A complete lifelong travel history is important for diagnosis. Many patients do not have a clear history of acute schistosomiasis. Many patients have few or mild symptoms. Individuals with symptoms may present with nonspecific complaints reflecting their level of infection, the primary location of egg production for the schistosomal species involved (eg, mesenteric, bladder wall), the extent of hepatosplenic involvement, the extent of cardiopulmonary involvement, and the presence of ectopic sites (eg, CNS). Those who present to the ED setting are most likely to complain of the following:  
• • Bloody diarrhea
  • Abdominal pain, RUQ pain, cramping
  • Hematemesis (with portal hypertension)
  • Ascites (with portal hypertension)
  • Hematuria, dysuria
  • Vulvar or perianal lesions
  • Dyspnea on exertion (with pulmonary hypertension)
  • Fatigue (with pulmonary hypertension)
  • Cough (with pulmonary hypertension)
  • Palpitations (with pulmonary hypertension)
  • Atypical chest pain (with pulmonary hypertension)
  • Seizures and/or mental status changes (with cerebral involvement)
  • Paralysis (with spinal cord involvement)

Physical

Physical findings vary with the stage of illness, worm burden, worm location, and end-organ involvement.

• Acute schistosomiasis 
• • Fever
  • Hepatosplenomegaly
  • RUQ tenderness
  • Urticaria
  • Lymphadenopathy
  • Bloody stool
• Chronic schistosomiasis 
• • Hepatosplenomegaly
  • Abdominal tenderness
  • Heme-positive stool and/or bloody diarrhea
  • Ascites
  • Pedal edema (with right heart failure)
  • Seizures, focal neurologic signs, and/or altered mental status (with cerebral infection)
  • Paralysis (with spinal core involvement)
  • Vulvar or perianal lesions, which may be hypertrophic, ulcerated, or fistulous (Lesions may mimic sexually transmitted diseases.)

Causes

Most human schistosomiasis is caused by S haematobium, S mansoni, or S japonicum. Less prevalent species, such as S mekongi and S intercalatum, may also cause systemic human disease.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Cirrhosis
Pulmonary hypertension
Co-infection with malaria
Co-infection with HIV
Co-infection with hepatitis B or hepatitis C

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Blood tests are occasionally useful in supporting the diagnosis or assessing the severity of schistosomal infection. Serologies, and, more recently, polymerase chain reaction (PCR)–based testing can confirm a diagnosis.^{2, 3}
• A complete blood cell (CBC) count may reveal peripheral eosinophilia, particularly in acute infection, anemia, or both.
• Chemistries  
• • Increased alkaline phosphatase level and gamma-glutamyltransferase (GGT) level are observed with hepatic granulomatosis.
  • Transaminase levels generally are not affected, and elevations are usually caused by coexisting hepatitis.
  • Renal function may be decreased if obstructive nephropathy is severe.
• Blood cultures are indicated for patients with persistent or recurrent fever and for those who may have developed recurrent salmonellal infection with severe enteric schistosomiasis.
• Urine microbiology is key when diagnosing vesicular infection from S haematobium. Gross and microscopic hematuria is common. Concentration methods may be necessary, and a rough determination of egg-load can be obtained. However, this should not be used as a firm measure of disease severity as egg counts can vary markedly between specimens in one patient.
• Fecal microbiology, usually on thick smears, is key when diagnosing schistosomiasis with primary bowel infection. Stool specimens may be positive for heme or grossly bloody. Concentration methods will be needed to identify light infestations. Rough quantitation can also be performed in these specimens with the same limitations as above.

Imaging Studies

• Ultrasonography 
• • Ultrasonography (US) is a sensitive means of assessing hepatosplenic disease with periportal fibrosis or urinary obstruction.
  • It can demonstrate periportal fibrosis, splenomegaly, portal collaterals, periportal adenopathy, ureteral obstruction, and obstructive nephropathy.
• Echocardiography can demonstrate pulmonary hypertension and cor pulmonale, if present.
• Chest radiographs may show patchy infiltrates in acute schistosomiasis and can indicate pulmonary hypertension and cor pulmonale in end-stage chronic infection, if present.
• CT scanning may be useful in the evaluation of CNS disease or in the detection of periportal fibrosis.
• Magnetic resonance imaging (MRI) may be useful in the evaluation of CNS disease or in the detection of periportal fibrosis.

Other Tests

• Serology  
• • Enzyme-linked immunosorbent assay (ELISA) testing is available and can be helpful to confirm past exposure. However, antibody testing cannot distinguish active infection from inactive infection.
  • The use of schistosomal antigen testing to help distinguish between active and inactive infection is promising but unlikely to assist in emergency management.
  • Antigen titers from serum and urine correlate with the degree of infection, as indicated by concomitant egg counts.
  • These tests may be particularly useful during acute or end-stage disease, when egg shedding can be minimal.
• Microscopy  
• • The finding of schistosomal eggs in the urine supports a definitive diagnosis.
  • Urine samples can be examined qualitatively after centrifuging. However, eggs are not shed at a steady rate during the day, and quantitative egg counts are useful for determining the degree of infestation and response to therapy. Therefore, 24-hour urine collections may be recommended.
  • The finding of schistosomal eggs in the stool supports a definitive diagnosis.
  • Stool specimens usually are examined in a thick smear clarified with glycerol (Kato-Katz technique). Schistosomal species can be distinguished using egg morphology.
  • Microscopy is not part of a standard ova and parasite evaluation and must be ordered specifically.
  • Quantitative evaluation allows assessment of the degree of infection and treatment response.
  • Hatching assays may be performed on fresh stool specimens to distinguish active from treated infection because dead eggs may be shed for up to 1 year after treatment.

Procedures

• Colonic biopsy  
• • Use of multiple crush specimens from the colon and/or rectum to visualize parasite eggs is a sensitive and specific test for enteric schistosomiasis.
  • In the United States, where schistosomiasis is rare, most cases are diagnosed by this method.
• Cystoscopy may be useful in schistosomiasis with primary bladder involvement for definitive diagnosis or to evaluate secondary ulcers and polyps, biopsy for malignancy, rule out other sources of hematuria and dysuria, and identify eggs in mucosal biopsy specimens.
• Endoscopy and sclerotherapy may be indicated emergently in the presence of hematemesis caused by portal hypertension.
• Liver biopsy may be appropriate in patients with unclear diagnoses or suspected co-infections.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Support and stabilization are provided for acute complications of infection, if present. These might include volume depletion, heart failure, and gastrointestinal (GI) bleeding.

Emergency Department Care

In the ED, the physician confirms the diagnosis, begins antibiotic therapy, and stabilizes patients with acute complications of schistosomiasis. Management of hepatosplenic, gastrointestinal, urinary, cardiopulmonary, and CNS complications are summarized briefly below. Readers are referred to articles on these topics for a more comprehensive discussion of procedures.

• Volume depletion secondary to diarrhea is rarely severe. It is treated with intravenous or oral volume replacement. Minor lower GI bleeding may be present but rarely requires transfusion.
• In portal hypertension with hematemesis, treatment with fluid resuscitation, transfusion, endoscopic treatment, or surgery may be required.
• Urinary obstruction may require stenting or other drainage procedures.
• Salmonellal sepsis may require antibiotics and fluids.
• Pulmonary hypertension and cor pulmonale may require oxygen, diuresis, antiarrhythmics, or other interventions.
• Cerebral infection may require seizure control or management of intracranial pressure.
• Transverse myelitis may require steroids and supportive care as well as antihelminthic therapy.
• Corticosteroids may be needed in the management of acute schistosomiasis to suppress the hypersensitivity reaction, which may worsen at first with antihelminthic treatment.

Consultations

• Clearly communicating with the hospital's diagnostic laboratory personnel is crucial for optimal egg detection in stool and urine specimens.
• Consult specialists as indicated by the complications present (see above) or the need for diagnostic procedures, such as colonoscopy.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Definitive therapy can be initiated and often completed in the ED if the diagnosis is clear. During acute infections, treatment may exacerbate symptoms as a result of increased antigen release, usually requiring corticosteroid support. Treatment may produce a Loefflerlike syndrome in cases of heavy infestation, which may require pulmonary support.

Schistosomiasis is unusual in that only one drug, Praziquantel, see below, is widely in use. Drug resistance has been reported and can be produced in laboratory settings but appears still to be uncommon in human infections. Myrrh derivatives have not demonstrated success in testing, but artemisinins⁴ are showing efficacy, and trioxolanes⁵ also show promise as future drugs.

Drug Category: Anthelmintics

Drug regimens result in curing the infection in 60-98% of cases and reduce egg burden in the remainder. Dead eggs may continue to shed for months, but treatment should arrest egg-laying, granuloma formation, and future complications. Although frank fibrosis may not reverse, evidence indicates that portal and pulmonary hypertension from granulomatous changes may improve significantly after treatment, particularly in younger patients.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Initiate inpatient care for unstable patients with complications, such as GI bleeding, decompensated heart failure, and toxicity, according to the usual indications.
• Inpatient care is indicated for CNS infections.

Further Outpatient Care

• Reevaluate patients for symptom resolution and determination of cure. For uncomplicated cases, 4-6 weeks is the optimal follow-up time, corresponding with the maturation of eggs and immature worms that may have survived initial treatment.
• Response may be evaluated by quantitatively decreased egg counts from urine or stool specimens or by antigen testing. Some patients require re-treatment.
• Patients with evidence of portal hypertension, pulmonary hypertension, CNS infection, or urinary obstruction require long-term follow-up care.

In/Out Patient Meds

• Treat schistosomiasis with definitive antihelminthic therapy, as described above (see Medication).

Deterrence/Prevention

• Travelers to endemic areas should avoid exposure to freshwater that is likely to be contaminated. No accepted prophylactic regimens have been developed, and no vaccines are currently available, although vaccine development is increasingly promising. Early treatment after high-risk exposures should minimize morbidity.
• Prevention for groups residing in endemic areas is more difficult than prevention for travelers.
• • Improved sanitation to decrease freshwater contamination with sewage should decrease disease prevalence.
  • Behavioral interventions to decrease occupational and recreational contact with contaminated water may be useful. These interventions are particularly problematic with children.
  • Molluscicides to decrease the prevalence of the snail hosts have some usefulness but require frequent reapplication and are used less frequently now than in the past.
  • Mass treatment of targeted populations with the newer less toxic antischistosomal agents may have utility. It can be combined with molluscicide treatment if needed.
  • Vaccines hold the promise of significantly reducing infection in endemic areas.
  • Genomic studies of the parasites may lead to improved therapeutics.

Complications

• End-organ disease
• Pulmonary hypertension
• Cor pulmonale
• Portal hypertension
• Obstructive uropathy
• Gastrointestinal bleeding
• Pregnancy complications from vulvar or fallopian granuloma
• Carcinoma of the liver, bladder, or gallbladder

Prognosis

• Almost all patients improve with treatment.
• Most patients with early disease or without severe end-organ complications recover completely.
• Surprisingly, patients with hepatic and urinary disease, even with fibrosis, may improve significantly over months or years following treatment.
• Resolution of pulmonary disease is less well documented.
• • Patients with heavier worm burdens are less likely to improve and are more likely to require re-treatment.
  • Treatment is indicated for patients with end-stage complications of portal hypertension and severe pulmonary hypertension, but these patients are much less likely to benefit.
• Co-infection (with malaria, HIV, or hepatitis) worsens the prognosis.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Taking a complete travel and residence history and considering the diagnosis of schistosomiasis in appropriate patients who present with nonspecific findings, such as fever, bloody diarrhea, hematuria, portal hypertension, pulmonary hypertension, or CNS abnormalities, are important. Antischistosomal treatment can arrest or improve many of these processes and prevent further complications.

Special Concerns

• Pregnancy: Physicians may prefer to defer treatment until after the first trimester.
• Pediatric
• • Pediatric and adolescent patients who have traveled or lived in endemic areas are at the highest risk for exposure to schistosomes and are at risk for serious long-term complications.
  • These patients usually respond well to drug therapy and should receive aggressive treatment and follow-up care.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Apr 2, 2008