Schistosomiasis

Lawrence Proano, MD, DTM&H
Robert Partridge, MD, DTM&H

Schistosomiasis, a parasitic disease, has plagued humans since ancient Egyptians times. The disease was known as far back as 3200 B.C. Schistosome eggs and antigens have been found in Egyptian mummies, and papyrus documents have been discovered that describe the disease and discuss remedies for it.1,2

Schistosomiasis is still common, and is emerging where it has not been previously identified, the result of man-made or environmental changes, or major population migrations. In the Senegal River Basin in Africa, for example, population migrations combined with dams and crop irrigation projects has increased the incidence from virtually non existent 3 years ago to a prevalence of greater than 95%.3

There are three main types of human schistosomes: S. Mansoni, S. Hematobium, S. and japonicum. Humans become infected usually by immersing themselves partially or entirely in fresh water that contains infected cercariae. In endemic areas, any standing or moving untreated fresh water, whether natural or man-made (in irrigation projects or inadequately heated bath water, for example), may contain infective cercariae. Travelers who swim, wade, kayak, raft or hike in wetlands in endemic areas are also at risk for infection.

Epidemiology. Schistosomiasis is endemic in 74 countries in Africa, Asia, the Caribbean, and South America, with an estimated 200,000,000 cases and 800,000 deaths annually. Travel to these areas is increasing. Therefore health-care providers need to be aware of the disease. In addition, brief and even single exposures to fresh water have been associated with infection (seropositivity). In two studies, in Mali, and in Malawi, of previously unexposed, generally asymptomatic expatriates 28 of 29 (97%) and 142 of 427 (33%) were seropositive.4,5 Two separate cases of severe central nervous system schistosomiasis occurred among Peace Corps volunteers with recreational water exposure in Lake Malawi.6

Life Cycle. Humans are the definitive host of the human schistosomes, and an accidental host of other schistosome species (those infecting birds and other mammals). Non-human schistosomes usually cause only an irritating, self limited dermatitis.

The life cycle of human schistosomes is well described. Snails are the intermediate host. The cycle begins with the shedding of eggs from man in stool and urine. The eggs hatch in fresh water and release the larval form (miracidiae). These migrate to the intermediate host (snails). In weeks to months they mature into cercariae, and are then released from the snail into the water. The cercariae are the infective agents for humans, the definitive host.

The cercariae penetrate exposed skin, and reach the vascular system. Now called schistosomules, schistosomula go to the lungs and then liver. They circulate in the hepatic sinusoids and develop into adult worms. Worms pair in the liver, and migrate to various organ systems, where eggs are deposited. S. Mansoni migrates predominantly to mesenteric venules of the colon, S. Hematobium predominantly migrates to the venules of the bladder and genitourinary system. Mature eggs penetrate the lumen of the colon or bladder, and are excreted, completing the life cycle.

Pathology. The pathologic lesions of schistosomiasis are caused by several distinct mechanisms. With S. Mansoni and S. Japonicum infections, the eggs contain organic substances that induce granuloma formation and macrophage and eosinophil accumulation in tissues. They also induce lymphocyte activity stimulating fibroblast proliferation and portal fibrosis. The fibrosis ultimately leads to severe portal hypertension, esophageal varices, and ascites. These are the signs of long term schistosomiasis. Since the fibrous portal triads resemble the stem of a clay pipe, the lesions are termed "pipe-stem fibrosis". With S. Hematobium infections, egg deposition leads to granuloma formation within the wall of the bladder. Ultimately, fibrosis of the bladder and ureters leads to obstruction, hydronephrosis and recurrent urinary infections. There is a well described association between chronic S. Hematobium infections and squamous cell carcinoma of the bladder.

Clinical Presentation. The classic disease presentation is characterized by three clinical stages. Initially, cercarial penetration results in a transient pruritic rash ("swimmer’s itch"). This first stage can occur up to 3 days after contact. The onset of the second stage of illness ranges from 3 to 8 weeks, and is often asymptomatic. During this stage, the schistosomules migrate to the lungs and during their passage through the lungs can induce a transient dry, nonproductive cough and nocturnal fevers. Less commonly seen signs include arthralgias, headache, diplopia, anorexia, nausea, weight loss, and scrotal itching.

Acute schistosomiasis occurs with the onset of egg deposition. In its more severe form, Katayama Fever, there is a serum sickness like syndrome, characterized by fever, chills, diaphoresis arthralgias, periorbital headache, dry non-productive cough, diarrhea, anorexia, and weight loss. Delerium and urticaria occur less commonly. Egg depostion occurs in either the bladder (S. Hematobium) or colon and rectal mucosa (S. mansoni or japonicum). Symptoms and signs usually disappear within a few weeks, but death may occur, particularly with S. japonicum. On physical examination, one generally finds enlargement of the liver, spleen, and lymph nodes.

Katayama Fever is more often noted in people who live outside the main endemic region of the disease and is the form commonly seen in travelers. Also, the more acute form is more often seen with S. japonicum, due to its greater production of worm and egg production, about ten times that of S. mansoni. It is unclear whether the acute form represents an immune complex disease, or a simple hypersensitivity and secondary inflammatory response.

The third stage is characterized by the late complications of the disease, generally years after an unrecognized infection. At this stage, the eggs induce chronic fibrotic scarring and granuloma formation. With S. mansoni, S. japonicum, the GI system is involved in the third stage, and there is secondary embolization of eggs to the liver. As a consequence, hepatic fibrosis ultimately results with accompanying portal hypertension. Liver cell perfusion is maintained however, so liver function tests remain normal until end stage disease results. Jaundice, hematemesis from varices, and ascites often result.

With S. Hematobium, the urinary tract is involved in the third stage of schistosomiasis. The granulomatous response here leads to urinary tract mucosal scarring and fibrosis. Secondary hydronephrosis and calcification of the GU tract results. An increased incidence of squamous cell carcinoma of the bladder has been noted with people with chronic S. Hematobium infections.

The differential diagnosis of patients who present during the second stage with the toxemic symptoms of Katayama fever includes malaria, brucellosis, mononucleosis, miliary tuberculosis, invasive strongyloidiasis or ankylostomiasis, trichinosis, visceral larval migrans and Churg-Strauss syndrome.7

Diagnosis. The first step in making the diagnosis of schistosomiasis is eliciting a travel history with fresh water exposure in endemic areas. Direct evidence of infection involves finding characteristic schistosome eggs in the urine or stool, usually in the third stage, and generally 5-12 weeks after exposure. If microscopic urinary and stool specimens are negative, then sigmoidoscopy, proctoscopy and cystoscopy may be helpful in identifying inflammatory changes or lesions in the colon or bladder mucosa. Rectal biopsy or snips may also be used. Schistosome eggs are more likely to be passed in the urine between the hours of 10 am and 2 pm. Eggs in the stool can be found at any time, although several stool specimens may need to be collected. A concentration technique should be used rather than a direct smear to increase sensitivity.

Peripheral blood analysis may yield some clues. Eosinophilia should be prominent in most cases, even in early stages of the disease. Indirect serologic testing using the ELISA technique is both sensitive and specific for human schistosomiasis, but is not available in all laboratories. ELISA serology may be positive in the second (acute) stage of disease 3-8 weeks after exposure. Other immunoassays have poor sensitivity and specificity and are known to give false positive results after exposure to avian schistosomes.

One problem with a positive serology is that it does not distinguish acute infection from prior exposure. Serology may remain positive long after treatment. However, in practice few clinicians go the extreme of invasive rectal biopsy to make the diagnosis. Many would choose to treat empirically a traveler with a history of potential exposure, symptoms from which to suspect the disease, and a positive serology, even with negative stools.

In later, chronic stages of this disease, liver biopsy and ultrasonography to assess for calcification of the liver, kidneys, ureters and bladder may be considered. Clinicians should always bear in mind that chronic salmonella infection may be associated with schistosome infection. S. Hematobium infection is associated with chronic urinary Salmonella Typhi infection, and S. Mansoni is associated with chronic Salmonella species septicemia. The Salmonella infection can only be cured after the patient has been treated for schistosomiasis. Human schistosome infection may also be associated with hepatitis B and C infection, and may increase the risk of transmission of HIV in females.

Treatment and Prevention. Praziquantel is effective against all human schistosomes and is considered the drug of choice. The dose is 40mg/kg orally as a single dose for S. Hematobium, and 30mg/kg orally for 2-3 doses for S. Mansoni and S. Japonicum. Mild gastrointestinal disturbance, headache and dizziness are common side affects, but are usually transient. Praziquantel should be avoided in the first trimester of pregnancy. Some treatment failures have occurred when treating S. Mansoni infection with praziquantel. In such refractory cases, oxamniquine, given at a dose of 10mg/kg, twice on the same day may be effective.

Persons traveling to endemic areas should be advised of the risk of schistosome infection as a result of freshwater contact, especially in marshes, shallow lakes and streams, or by whitewater rafting or canoeing. Schistosomiasis is not just a rural disease, and is now known to be endemic in a number of large African cities. There is currently no vaccine available against human schistosomes. Although the clinical outcome in travelers is usually complete recovery, hospitalization is sometimes necessary and symptoms can be severe. Transverse myelitis with subsequent paraplegia has been reported in travelers in Africa.

If skin contact with water cannot be avoided, some measures can be taken to avoid cercarial penetration. Before water exposure, the use of skin cleansers containing hexachlorophene may be effective, as is the use of soap while bathing. After water exposure, a rapid rubdown with a dry towel may reduce the risk of cercarial penetration. Applying alcohol to the exposed skin is also effective. Water for bathing can be made safer by storing it in a tank for at least 48 hours or heating it to 50 degrees C for 5 minutes. Both of these methods significantly reduce the number of infective cercariae. Finally, there is some evidence of anticercarial activity in vitro8 and in vivo9 using DEET, although larger trials are needed to establish efficacy.

Bibliography

1. Ruffer M. Note on the presence of Bilharzia Haematobium in Egyptian mummies of the twentieth dynasty (1250-1000 B.C.). Br Med J. 1910; 1:16.
2. Deelder AM, Miler Rl, de Jonge N, Krijger FW. Detection of antigen in mummies. Lancet. 1990; 335:724-725.
3. Grysells B, Stelma FF, Talla I, van Dam GJ, Polman K, Sow S, et al. Epidemiology, immunology and chemotherapy of Schistosoma mansoni infections in a recently exposed community in Senegal. Trop Geogr Med. 1994;46:209-219.
4. Cetron MS, Chitsulo L, Sullivan JJ, et al: Schistosomiasis in Lake Malawi. Lancet 348:1274-1278, 1996
5. Visser LG, Polderman AM, Stuiver PC: Outbreak of schistosomiasis among travelers returning from Mali, West Africa. Clin Infect Dis 20:280-285, 1995
6. Anonymous: Schistosomiasis in U.S. Peace Corps volunteers—Malawi, 1992 [published erratum appears in MMWR 42:615, 1993]. MMWR 42:565-570, 1993
7. Joubert, JJ, Evans, AC, Schutte, CHJ. Schistosomiasis in Africa and International Travel. J Travel Med. 2001; 8:92-99.
8. Secor WE. Short report: prevention of Schistosoma mansoni infections in mice by the insect repellents AI3-37220 and N,N-diethyl-3-methylbenzamide. Am J Trop Med Hyg. Jun 1999; 60(6): 1061-2.
9. Salafsky B. Development and evaluation of LIPODEET, a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of schistosomiasis. Am J Trop Med Hyg. Nov 1999; 61(5): 743-50.

(Larry and Rob are full time faculty for the Brown University Emergency Medicine Residency Program, based at Rhode Island Hospital in Providence, Rhode Island. In addition, they are diplomates of the School of Tropical Medicine at the Royal College of Surgeons, Dublin Ireland. Rob also has an MPH from Harvard University, and co-directs the Injury Prevention Center at Rhode Island Hospital. Together, they started a Travel Medicine Clinic this past year (TravelCare, Inc.), within the confines of a local Freestanding Urgent Care Center.)