Infectious Diseases

Schistosomiasis

OVERVIEW: What every clinician needs to know

Parasite name and classification

Helminths – phylum Platyhelminthes, class Trematoda. Main species infecting humans are Schistosoma haematobium, S. japonicum, and S. mansoni. Others include S. mekongi and S. intercalatum; some species which parasitize birds and mammals can rarely cause dermatitis in humans.

What is the best treatment?

  • Drug and dose: Praziquantel is the drug of choice for infections caused by all Schistosomaspecies - 60-90 percent cure rate, greater than 99 percent decrease in worm burden and egg production in those not cured. Taken orally with food at 40mg/kg in two divided doses for S. mansoni, S. haematobium and S. intercalatum; 60mg/kg in two to three divided doses for S. japonicum and S.mekongi; one day course.

  • Mechanism and useful tips: Praziquantel directly kills susceptible adult schistosomes; in addition the dead worms are dislodged from their usual site of residence in the mesenteric or pelvic veins to the liver where they undergo phagocytosis. The timing of treatment is important since Praziquantel is most effective against the adult worm (it does not kill immature worms or miracidium that are 3 to 21 days old) and requires the presence of a mature antibody response to the parasite. For travelers, treatment should be at least 6-8 weeks after last exposure to potentially contaminated freshwater. Retreatment is usually recommended 4-6 weeks after the first dose when treating early infections. If initially positive, reexamination of feces or urine one month after treatment is recommended in order to assess clearance.

  • Resistance concerns and alternatives: Limited concerns of parasite resistance based on low cure rates in some heavily exposed populations; however widespread clinical resistance has not occurred:

    • Mechanism: drug tolerant worms may have altered tegumental architecture which could limit drug efficacy.

    • Alternative therapies: 1) Artemether, a derivative of the antimalaria drug artemisinin, is effective against S. haematobium. S.mansoni and S.japonicum including young schistosomulae. Cure rates of up to 82 percent with a single dose and 100 percent with multiple dose therapy are reported. 2) For S. mansoni, oxamniquine in doses of 40-60mg/kg as a single oral dose (reported efficacy around 80 percent, documented resistance in Brazil and Kenya). 3) For S. haematobium, an alternative is metrifonate at 10mg/kg single oral dose (60-80 percent reported cure)

What are the clinical manifestations of infection with this organism?

  • Key symptoms: Incubation period for acute schistosomiasis is usually 14-84 days; most people have no symptoms when first infected. However, within days of becoming infected, they may develop a limited rash or itchy skin. Within 1-2 months, acute infection (also known as Katayama syndrome or snail fever) may present with a nocturnal fever, rash, headache, myalgias, abdominal discomfort and respiratory symptoms. Without treatment, schistosomiasis can persist for years; manifestations of chronic schistosomiasis include abdominal pain, enlarged liver, blood in the stool or in the urine, and problems passing urine. Chronic infection can also lead to increased risk of bladder cancer. Rarely, eggs are found in the brain or spinal cord and can cause seizures or paralysis.

  • Key physical findings: In acute infection - rash, hepatomegaly, and/ or splenomegaly; In chronic infection - sequelae of chronic disease and blood loss (pallor due to anemia) and of bladder inflammation (hematuria, hydronephrosis) or hepatic inflammation (ascites and/ or splenomegaly secondary to portal hypertension)

Do other diseases mimic its manifestations?

  • Eosinophilia can be secondary to other parasitic infestations

  • False positive schistosoma serology can be due to other viral infections (including Hepatitis B, Hepatitis C, HIV) that cause an increase in polyclonal immunoglobulins

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis:

  • Peripheral white blood cells (WBC) with differential: eosinophilia is usually present; anemia can be seen in chronic infection (either anemia of chronic disease or iron deficiency secondary to blood loss)

  • Urinalysis may show microscopic or macroscopic hematuria in S. haematobium

  • Screening following freshwater exposure in an endemic area may consist of a full blood count, absolute eosinophil count, Schistosoma serology, and urine and/ or fecal microscopy for eggs. This may be best done at 3-6 months post travel in asymptomatic individuals to decrease the number of false positive tests

Results that confirm the diagnosis

  • Stool and/ or urine tests for eggs: Gold standard is to demonstrate eggs in stool or urine. The choice of sample depends on the species of parasite likely causing the infection – a careful review of travel and residence history is critical for determining whether infection is likely and which species may be causing infection. Adult stages of S. mansoni, S. japonicum, S. mekongi, and S. intercalatum reside in the mesenteric venous plexus of infected hosts and eggs are shed in stool; S. haematobium adult worms are found in the venous plexus of the lower urinary tract and eggs are shed in urine. The eggs tend to be passed intermittently and in small amounts and may not be detected. Testing of stool or urine can be of limited sensitivity, particularly for travelers who may have lighter burden infections. To increase the sensitivity of stool and urine examination, three samples should be collected on different days. Egg appearance is the method to identify species - S. mansoni eggs are large (114-180 μm long, 45-70 μm wide) and have a characteristic shape, with a prominent lateral spine near its posterios end; S. haematobium eggs are large (110-170 μm long, 40-70 μm wide) and have a conspicuous terminal spine; S. japonicum are more rounded (70-100 μm long, 55-64 μm wide) and the spine is smaller and less conspicuous than other species.

  • Blood test - serologic testing for antischistosomal antibody is indicated for diagnosis of travelers or immigrants from endemic areas who have not been treated appropriately for schistosomiasis in the past. Commonly used serologic tests detect antibody to the adult worm. For new infections, the serum sample tested should be collected at least 6 to 8 weeks after likely exposure, to allow for full development of the parasite and antibody to the adult stage. Serologic testing may not be appropriate for determination of active infection in patients who have been repeatedly infected and treated in the past because specific antibody can persist despite cure. In these patients, serologic testing cannot distinguish resolved infection from active infection.

  • Histopathologic exam of superficial mucosal biopsies from rectal mucosa is the most sensitive test for hepatic forms, but this invasive procedure is rarely indicated. With S. haematobium, the most sensitive test is to centrifuge an entire morning urine collection and examine its sediment.

What imaging studies will be helpful in making or excluding the diagnosis of schistosomiasis ?

  • Chest X-ray (CXR) ($): may be normal; in acute infection may show patchy pulmonary infiltrates. More pronounced radiological findings include thickening of bronchial walls and beaded micronodulation in the lower pulmonary fields.

  • Ultrasound or abdominal computed tomography (CT) scan ($$) - For S. mansoni and S. japonicum infection, liver imaging allows identification of characteristic periportal fibrosis and defines the level of disease associated with parasite infection. In S. haematobium infection, ultrasound examination of the kidneys and bladder allows identification of granulomas, hydronephrosis, and other inflammatory changes.

What complications can be associated with this parasitic infection, and are there additional treatments that can help to alleviate these complications?

Clinical manifestations of chronic disease result from host immune responses to schistosome eggs.

Gastrointestinal (GI) and hepatic

S. mansoni and S. japonicum eggs most commonly lodge in the blood vessels of the liver or intestine and can cause diarrhea, constipation, and blood in the stool. Chronic inflammation can lead to bowel wall ulceration, hyperplasia, and polyposis and, with heavy infections, to hepatic perisinusoidal egg granulomas, Symmers' pipe stem periportal fibrosis, and when further advanced, liver fibrosis and portal hypertension.

Genitourinary tract

S. haematobiumeggs tend to lodge in the urinary tract causing mucosal damage, dysuria and hematuria. Chronic infections may increase the risk of bladder cancer. S. haematobium egg deposition has also been associated with damage to the female genital tract, causing female genital schistosomiasis that can affect the cervix, fallopian tubes and vagina, and lead to increased susceptibility to other infections.

Pulmonary

Pulmonary hypertension and Cor Pulmonale.

Central nervous system

Central nervous system (CNS) lesions have been reported, but are rare. Disease is the result of ectopic deposition of eggs in the spinal cord (S. mansoni or S. haematobium) or brain (S. japonicum) and inflammatory reactions, typically the formation of granulomas that act as space occupying lesions. CNS infection is treated with longer antiparasitic therapy along with corticosteroids and/ or anticonvulsants. Symptomatic ectopic infection may initially worsen with therapy due to a local inflammatory response.

What is the life cycle of the parasite, and how does the life cycle explain infection in humans?

  • Parasite life cycle (see reference 2 for link to image of life cycle)

    • Stages of development: Schistosoma eggs exit the human body with feces or urine (diagnostic stage). Under optimal conditions the eggs hatch and release miracidia, which swim and penetrate species-specific snail intermediate hosts. The stages in the snail include 2 generations of sporocysts and the production of cercariae. Upon release from the snail, the cercariae (infective stage) swim and penetrate the skin of the human host. They shed their forked tail, becoming schistosomulae which migrate through several tissues and stages to their residence in the veins. Adult worms in humans reside in the mesenteric venules in various locations, which at times seem to be specific for each species. For instance, S. japonicum is more frequently found in the superior mesenteric veins draining the small intestine, and S. mansoni occurs more often in the superior mesenteric veins draining the large intestine. S. haematobium most often occurs in the venous plexus of bladder, but it can also be found in the rectal venules. The females (size 7 to 20 mm; males slightly smaller) deposit eggs in the small venules of the portal and perivesical systems. The eggs are moved progressively toward the lumen of the intestine (S. mansoni and S. japonicum) and of the bladder and ureters (S. haematobium), and are eliminated with feces or urine, respectively.

    • Key vectors for transmission to humans: Snails are the intermediate host - thus the name "snail fever" for acute infection. These are Biomphalaria species snails for S. mansoni, Bulinus for S. haematobium and Oncomelania for S. japonicum.

    • Seasonal differences in incidence: Infections possibly peak in the summer season, and decrease in the winter season.

    • Environmental conditions that predispose to infection: Activities that can lead to contact with infested water range from wading, bathing and swimming to scuba diving, water skiing and rafting. Contaminated water sources include canals, lakes, rivers, streams, and springs.

    • Prevalence and geographic distribution: Schistosoma mansoni is found in parts of South America and the Caribbean, Africa and the Middle East; S. haematobium in Africa and the Middle East; and S. japonicum in the Far East. S. mekongi and S. intercalatum are found focally in Southeast Asia and Central and West Africa, respectively.

    • Susceptible individuals and populations: School age children in endemic areas are most susceptible; other people at risk are those involved in agricultural, domestic or recreational activities exposing them to infested water. Most cases in western travel clinics are imported from sub-Saharan Africa, often in family or group clusters. Frequent sources of infection include Lake Malawi, Lake Victoria, and Lake Volta, the Zambesi and Niger deltas, and lake resorts in South Africa.

    • Incidence and trends: Per the WHO, incidence of schistosomiasis was 33.5 million cases in 2010, which is an increase compared with 12.4 million cases in 2006.

  • Prevention

    • Anti-infective prophylaxis is currently not recommended.

    • No vaccine is currently available.

    • Strategies for avoiding exposure to the vector when in endemic regions : 1) avoiding swimming or wading in fresh water 2) drinking safe water (water coming directly from canals, lakes, rivers, streams and springs may be contaminated unless filtered or brought to a rolling boil for 1 minute) 3) using similar precautions for water used for bathing or using water held in a storage tank for at least 1-2 days 4) vigorous towel drying in case of any accidental brief contaminated water exposure.

    • Methods to eliminate the vector/ intermediate host or interrupt its life cycle: In countries in which schistosomiasis is endemic, control efforts usually focus on two areas 1) reducing the number of infections in people (by mass treatment of entire communities and focused treatment of school age children, and by improved sanitation) and 2) eliminating the snails that are required to maintain the parasite's life cycle (using chemical measures).

How does these organisms cause disease?

  • Schistosoma parasites can penetrate the skin of persons who come in contact with contaminated fresh water in which certain types of snails that carry the parasite are living. This occurs typically when wading, swimming, bathing, or washing. Over several weeks, the parasites migrate through host tissue and develop into adult worms inside the blood vessels of the body. Once mature, the worms mate and females produce eggs. Eggs are deposited in the capillaries of the target organ that is parasitized by the breeding pair of worms. With Schistosoma haematobium, this is the urinary system as well as the sacral and pelvic vessels, whereas with intestinal schistosomiasis (S. mansoni, S. japonicum, S. intercalatum, and S. mekongi) parasitization occurs in the intestinal mucosa. Once deposited, a proportion of the eggs then enter the lumen of the bladder or intestines.

  • Symptoms of schistosomiasis are caused not by the worms themselves but by the body’s reaction to the eggs. Acute infection (Katayama syndrome) is a systemic hypersensitivity reaction against the migrating schistosomula and eggs. Eggs shed by the adult worms that do not pass out of the body can become lodged in the intestine or bladder, causing inflammation or scarring. Children who are repeatedly infected can develop anemia, malnutrition, and learning difficulties. After years of infection, the parasite can also damage the liver, intestine, spleen, lungs, and bladder.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

"Centers for Disease Control and Prevention: Schistosomiasis".

(A helpful resource from the CDC for information including additional global health links.)

"Laboratory Identification of Parasites of Public Health Concern: Schistosomiasis".

(Diagnostic images of eggs of S. haematobium, S. japonicum, S. mansoni, S.mekongi and S.intercalatum; and graphic depiction of life cycle of Schistosoma)

Liu, R, Dong, HF, Guo, Y, Zhao, QP, Jiang, MS. "Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis". Parasit Vectors. vol. 17. 2011. pp. 201.

(Compilation of the evidence for Praziquantel and Artemisinin derivatives.)

Keiser, J, N'Guessan, NA, Adoubryn, KD. "Efficacy and safety of mefloquine, artesunate, mefloquine--artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open label trial". Clin Infect Dis. vol. 50. 2010. pp. 1205-13.

Ross, AG, Vickers, D, Olds, GR. "Katayama syndrome". Lancet Infect Dis. vol. 7. 2007. pp. 218-24.

(A good review focusing on acute Schistosomiasis)

Ross, AG, Bartley, PB, Sliegh, AC. "Schistosomiasis". NEJM. vol. 346. 2002. pp. 1212-20.

(Another good review of Schistosomiasis.)
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