FINAL DIAGNOSIS: SCHISTOSOMIASIS
Schistosomiasis, also sometimes referred to as "bilharziasis" after Theodor Bilharz who identified the parasite in 1852, is caused by infection with parasitic blood-dwelling fluke worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta, specific freshwater snails as intermediate hosts, and human water contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum.
The World Health Organization estimates more than 200 million people worldwide have schistosomiasis, and that the infection is responsible for more than 200,000 deaths annually. Schistosomiasis is associated with significant morbidity including anemia, chronic pain, diarrhea, exercise intolerance, malnutrition, bladder cancer, portal hypertension, and CNS complications. Although most infections occur in residents of endemic areas, it has been clearly documented that travels with only brief freshwater exposure may become infected. Schistosomiasis species tend to occur in restricted geographic patterns. S. mansoni is most prevalent in certain tropical and subtropical areas of sub-Saharan Africa, the Middle East, South America and the Caribbean. S. haematobium infection is acquired predominantly in North Africa, sub-Saharan Africa, the Middle East, Turkey, and India. S. japonicum occurs only in Asia, particularly in China, the Philippines, Thailand, and Indonesia. S. intercalatum occurs only in central and West Africa. S. mekongi is restricted to Laos and Cambodia In endemic areas, the infection is usually acquired in childhood.
The life cycle of schistosomiasis is complex and requires both intermediate and definitive hosts (Figure 7). Like all trematodes, schistosomes appear as unsegmented leaf-like organisms. The adult worms are approximately 1-2 cm in length, with a cylindrical body, two terminal suckers, a blind digestive tract, and reproductive organs. The male schistosome forms a groove or gynecophoric channel where the female resides. The females produce hundreds to thousands of eggs per day, depending on the species. After contact with water, each ovum releases a ciliated miracidium larva, which seeks an intermediate host, the snail. After four to six weeks, the miracidia multiply asexually into sporocysts and later into cercarial larvae. The cercariae leave the snail and seek a definitive host, where they develop into adult worms.
Humans acquire schistosomiasis via contact with freshwater containing the cercarial larvae, which are able to penetrate the intact skin of humans and become schistosomulae. Schistosomulae migrate from the skin into the blood and lymph vessels and are carried to the heart and lungs. They then migrate through the pulmonary capillaries into the left side of the heart and, from there, into the arterial circulation. They are carried to the mesenteric arteries, splanchnic arteries, and portal veins, subsequently reaching the liver where they mature into adults over a period of one to four weeks. Different species have a propensity to affect different organs. S. mansoni has an affinity for the mesenteric venules of the colon, S. japonicum tends to travel to the mesenteric venules of the small intestine, and S. haematobium prefers the vesical venous plexus. The adults remain in these blood vessels for life, and may survive for as long as 30 years. Adult schistosomes do not replicate within the host. After one to three months, the female worm begins to produce eggs, which travel hematogenously to other sites or can traverse from the vascular space through host tissues to the lumen of the intestine or urinary bladder. The eggs are excreted in the feces or the urine and can stay viable for up to seven days.
The percutaneous penetration of cercariae can provoke a temporary urticarial rash that sometimes persists for days as papulopruriginous lesions, especially after primary infections such as occur in tourists and migrants. Acute schistosomiasis, sometimes referred to as Katayama fever, is a systemic hypersensitivity reaction against the migrating schistosomulae. This typically occurs a few weeks to months after a primary infection, and symptoms start suddenly with fever, fatigue, myalgia, malaise, non-productive cough, eosinophilia, and patchy infiltrates on chest radiography. Abdominal symptoms can develop later, caused by the migration and positioning of the mature worms.
The main lesions in established and chronic infection are due not to the adult worms, but rather are due to entrapped eggs. The eggs secrete proteolytic enzymes that provoke typical eosinophilic inflammatory and granulomatous reactions, which are progressively replaced by fibrotic deposits. Schistosome eggs migrating through the intestinal wall provoke mucosal granulomatous inflammation, pseudopolyposis, ulcerations, and superficial bleeding. The most common symptoms are abdominal pain and discomfort, loss of appetite, rectal bleeding, and diarrhea. Schistosome eggs migrating through the vesical and ureteral walls provoke granulomatous inflammation, ulceration, and pseudopolyposis as well, and common early signs include dysuria, proteinuria, and hematuria. Chronic urinary schistosomiasis is associated with squamous bladder cancer.
Many people who are infected with schistosomiasis are asymptomatic, so detection of disease is often an incidental finding. Routine blood or urine tests may show nonspecific abnormalities. A routine blood count may show eosinophilia and/or anemia from chronic blood loss. Patients with hepatosplenic schistosomiasis may have thrombocytopenia secondary to splenic sequestration. Liver function tests including transaminases are usually normal since fibrosis occurs mainly within blood vessels and not within the liver parenchyma itself. However, a mild increase in alkaline phosphatase and gamma-glutamyl transferase may be present. S. haematobium infections are often associated with hematuria, which can be detected by urine dipstick.
The demonstration of schistosome eggs in the stool or urine remains the gold standard for the diagnosis of schistosomiasis, and is required for species identification. However, the sensitivity of microscopy may be low, especially in light infections. Schistosome eggs may also be revealed in tissue biopsy from the bladder or the gastrointestinal tract, as in our case. The different species of schistosomes are distinguished by morphologic differences in the eggs (Figure 8). S. mansoni eggs measure 115 to 175 micrometers by 45 to 70 micrometers and have a prominent lateral spine. S. haematobium eggs measure 110 to 170 micrometers by 40 to 70 micrometers and have a prominent terminal spine. S. japonicum measures 70 to 100 micrometers by 55 to 65 micrometers and has only a small inconspicuous spine. Mixed infections can occur.
Antibody-based serologic assays are available, which can detect antischistosomal antibodies in serum samples. These tests are quite sensitive, but cannot distinguish history of exposure from active infection. They can also cross-react with other helminths. Most routine techniques detect IgG, IgM, or IgE against soluble worm antigen or crude egg antigen by enzyme linked immunosorbent assay, radioimmunoassay, indirect hemagglutination, Western blot, or immunofluorescence. Seroconversion generally happens within 4-8 weeks of infection, but the interval can be as long as 22 weeks. Most assays have positive results for at least 2 years after cure, and in many cases much longer.
Schistosomiasis is also sometimes associated with serious neurologic complications. The two main clinical syndromes are spinal cord neuroschistosomiasis (acute or subacute myelopathy) and localized cerebral or cerebellar neuroschistosomiasis. Neurologic complications can occur even in individuals who are lightly infected; prevention of this complication is one of the main reasons that asymptomatic patients must be treated.
Pulmonary complications of schistosomiasis may occur with heavy infections and portal-caval shunting, which allows eggs to leak into the perialveolar capillary beds. The eggs lodge in pulmonary arterioles and produce a granulomatous pulmonary endarteritis. Pulmonary hypertension and cor pulmonale gradually develop.
Recurrent bacteremia is a complication seen with schistosomiasis infection, probably either due to enteric bacteria entering the bloodstream via damaged colonic mucosa or adult schistosomes serving as a reservoir as they ingest bacteria. Recurrent urinary tract infections and bacteremia due to Salmonella are classic complications of schistosomiasis. Eradication of the adult worms is recommended to prevent further relapses of bacterial infection.
A diagnosis of schistosomiasis should prompt initiation of treatment, even if the patient is asymptomatic, since adult worms can live for years. Praziquantel, an acylated quinoline-pyrazine anti-helminthic agent that is active against all schistosome species, is now the most widely used. It is dispensed as 600 mg tablets, with a recommended dosage of 40 mg/kg. The drug acts within one hour of ingestion by paralyzing the worms and damaging the tegument. Side effects are mild and include nausea, vomiting, malaise, and abdominal pain. Praziquantel has little or no effect on eggs and immature worms. Tissue-dwelling eggs can be excreted for several weeks after treatment, and prepatent or newly acquired infections may become productive. The preferred timing of follow-up is 4-6 weeks after treatment. 60 mg/kg or more in split doses may also be used for patients who have left the endemic area, to ensure complete cure. A repeat dose 6-12 weeks later can be useful to cure prepatent infections, particularly if eosinophilia, high antibody titers, or symptoms persist. Katayama fever is primarily treated with corticosteroids to suppress the hypersensitivity reaction and praziquantel to eliminate the already matured worms. Vaccines are not yet available.
The three major schistosomal species include S. mansoni and S. japonicum (associated with intestinal and hepatic pathology) and S. haematobium (associated with urinary tract pathology). Humans acquire schistosomiasis via contact with freshwater containing infectious, free-living, cercarial larvae. The majority of individuals with schistosomiasis are asymptomatic; however schistosomiasis can be associated with serious complications. The pathology is related to the host immune response to eggs present in the vasculature and tissue. Granulomatous inflammation occurs around the eggs, which can lead to fibrosis and scarring.
In this case, the foreign bodies identified in the biopsy specimen represent schistosome eggs lodged in the small venules of the colonic lamina propria. There is a classical brisk eosinophilic inflammatory response to the eggs. The colonic location, the approximate size, and the hint of a lateral spine all suggest these eggs most likely belong to the species S. mansoni. At this time, there has been no additional follow up from this patient with definitive stool microscopy or immunological testing.
Contributed by Amber Henry, MD and Shih-Fan Kuan, MD