Classification: Taxonomic ranks under review (cf. Encyclopedic Reference of Parasitology, 2001, Springer-Verlag)

Metazoa (Animalia) (multicellular eukaryotes, animals)
Platythelminthes (flatworms)
Cercomeridea (with oral sucker and bifurcate intestine)
Trematoda (trematodes, with posterior sucker)
Digenea (digenetic life-cycle, larval miracidia, snail vectors)
Strigeatida (miracidia with 2 pairs protonephridia, fork-tailed cercariae)

Family: Schistosomatidae
Unlike all other trematodes, schistosomes are not hermaphroditic but dioecious, forming separate sexes. Adult worms have elongate tubular bodies, each male having a unique gynecophoral canal (schisto-soma = split body) in which a female worm resides. They live inside visceral blood vessels and are commonly known as blood flukes. They have digenetic life-cycles involving aquatic snails as obligate intermediate hosts. Eggs deposited in the circulation penetrate the gut or bladder to be excreted with faeces or urine. In water, the eggs release miracidia which infect snails and undergo asexual proliferation through sporocyst stages eventually releasing cercariae back into the water. Vertebrate hosts become infected by direct penetration of the skin. Infections may cause chronic debilitating diseases in humans and some domestic animals.

Schistosoma spp. [these species cause schistosomiasis/bilharzia in humans and ruminants]

Parasite morphology: Blood flukes form five different developmental stages: eggs, miracidia, sporocysts, cercariae and adult worms. Eggs are round to oval in shape, operculate (hinged at one end) and contain a developing embryonic larva (miracidium). Differences in egg morphology can be used to distinguish between Schistosoma species: S. mansoni producing oval eggs (115-175 x 45-7µm) with a sharp lateral spine, S. japonicum forming round eggs (70-100 x 50-70µm) with a rudimentary lateral spine; and S. haematobium producing oval eggs (110-170 x 40-70µm) with a sharp terminal spine. Miracidia are elliptical free-swimming larval stages (~200µm long) covered with cilia. Sporocysts appear as pleomorphic sac-like bodies which contain developing cercariae. Mature cercariae are elongate free-swimming larval stages (400-600µm long) consisting of a tapering head (with prominent penetration glands) and a forked tail (furcocercous). Adult flukes are elongate tubular worms (10-20mm long), with rudimentary oral and ventral suckers. Males are shorter and stouter than females, and they have a longitudinal cleft (gynecophoral canal or schist) in which the longer slender female lies folded.

Host range: Schistosomes are important human and animal parasites throughout Africa, Asia and South America, predominantly in rural areas supporting agriculture and inland fisheries. Parasite distribution is linked to that of their snail intermediate hosts, which differ in their habitat preferences for slow-flowing or still waters. Many human activities also influence parasite distribution, especially the construction of irrigation channels and dams, and flood irrigation of crops. It has been estimated that over 200 million people may be infected worldwide. Infections have been recorded throughout human history, first being mentioned in ancient Egyptian papyri dated from 2000-1000 BC. Haematuria (bloody urine) became the scourge of Napoleon’s army in northern Africa at the turn of the 18th century, and the disease later became known as bilharzia in honour of the discoverer of the causative agent. Schistosoma spp. vary in their specificity for intermediate hosts, some only developing in humans (and possibly primates) while others may infect domestic and wild animals, acting as reservoirs for human infection.

Parasite species	Definitive host	Site of infection	Egg excretion	Snail vector	Geographic location
S.haematobium	humans, primates	veins of urogenital system	urine	Bulinus	Africa
S. mansoni	humans, rodents	intestinal mesenteric veins	faeces	Biomphalaria	Africa, America
S. japonicum	humans, ruminants, carnivores	intestinal mesenteric veins	faeces	Oncomelania	SE Asia
S. intercalatum	humans, rodents, cattle	intestinal mesenteric veins	faeces	Bulinus, Physopsis	Africa
S. mekongi	dog/cathumans	intestinal mesenteric veins	faeces	Oncomelania	SE Asia
S. bovis	ruminants	intestinal mesenteric veins	faeces	Bulinus	Africa, SE Asia, Middle East, Europe
S. mattheei	ruminants	intestinal mesenteric veins	faeces	Bulinus	Africa, Middle East

Site of infection: Paired adult worms live inside blood vessels in specific sites within the human body. S. mansoni lives principally in the portal veins draining the large intestine, S. japonicum in the mesenteric veins of the small intestines, and S. haematobium infects veins of the urinary bladder plexus. Fluke eggs penetrate into the lumen of the intestines or bladder to be voided with host faeces or urine. Many eggs, however, may be swept away in the host circulation and become trapped in various host tissues and organs.

Pathogenesis: Schistosomiasis (or bilharziasis) is unusual amongst helminth diseases for two reasons: much of the pathogenesis is due to the eggs (rather than larvae or adults); and most of the pathology is caused by host immune responses (delayed-type hypersensitivity and granulomatous reactions). The course of infection is often divided into three phases: migratory, acute and chronic. The migratory phase occurs when cercariae penetrate and migrate through the skin. This is often asymptomatic, but in sensitized patients, it may cause transient dermatitis (‘swimmers itch’), and occasionally pulmonary lesions and pneumonitis. The acute phase (sometimes called Katayama fever) is coincident with first egg release and is characterized by allergic responses (serum sickness due to overwhelming immune complex formation), resulting in pyrexia, fatigue, aches, lymphadenopathy, gastrointestinal discomfort and eosinophilia. The chronic phase occurs in response to the cumulative deposition of fluke eggs in tissues and the host reactions that develop against them. Not all the eggs laid by female worms successfully penetrate the gut or bladder walls, many are swept away in the circulation and become trapped in organs where they elicit strong granulomatous responses. Eggs become surrounded by inflammatory cells forming characteristic pseudotubercles, which may coalesce to form larger granulomatous reactions (polyps). The encapsulated eggs die and eventually calcify. The resultant effects on host organs and tissues are manifold, and include intestinal polyposis, abdominal pain, diarrhoea, glumerulonephritis, pulmonary arteritis, cardiovascular problems including heart failure, and periportal (Symmer’s clay pipe-stem) fibrosis. Portal hypertension often leads to hepatomegaly, splenomegaly, ascites, and sometimes gross enlargement of oesophageal and gastric veins (varices) which may burst. Cerebral granulomas have been associated with focal epileptic convulsions, while spinal cord granulomas may cause transverse myelitis. Infections by S. haematobium often cause haematuria (blood in urine) and progressive disruption of the bladder wall may lead to carcinoma.

Mode of transmission: Schistosomes have indirect digenetic life-cycles, involving sexual reproduction in vertebrate definitive hosts and asexual reproduction in snail intermediate hosts. Parasites are transmitted between hosts by motile aquatic stages which actively seek hosts. Female worms produce numerous eggs (200-3,000 per day) which seek to exit the host by penetrating the gut or bladder wall and being passed with host faeces or urine. When deposited in water, the embryonated eggs hatch releasing free-swimming miracidia which only live for several hours. In that time, they actively seek suitable intermediate hosts (amphibious snails) using chemotaxis and phototaxis (despite absence of eyespots). All Schistosoma spp. demonstrate quite narrow host specificity for particular snails: S. mansoni infects Biomphalaria spp. (large flat spiral snails ~14mm in diameter with ~3 whorls and apical aperture), S. japonicum infects Oncomelania spp. (small elongate snails ~8mm long with 4-5 whorls and dextral (right-sided) aperture), and S. haematobium infects Bulinus spp. (medium ovoid snails ~12mm long with 2-3 whorls and sinistral (left-sided) aperture). The miracidia invade the soft tissues of the snail and form a mother sporocyst near the site of penetration. Daughter sporocysts are produced 2-6 weeks after infection and they migrate to other organs in the snail. Schistosomes do not produce redia stages; instead the sporocysts produce cercariae which are released into the water in their thousands beginning 4 weeks after infection. The fork-tailed cercariae are rapid swimmers and they periodically swim to surface of the water and then sink to bottom for up to three days. They are attracted to skin secretions and when they come into contact with a prospective definitive host, they attach and actively penetrate the skin within minutes, losing their tails in the process. Inside the host, the schistosomula (little schistosomes) are carried in blood and/or lymph to the portal vessels in liver, where they develop for 3 weeks. Young worms then pair and migrate to their predilection sites in the veins of the gut or bladder. Egg production begins from 4-8 weeks after infection, and adult worms normally live for 2-5 years, although some may survive much longer.

Differential diagnosis: Infections are conventionally diagnosed by the detection of fluke eggs in faecal or urine samples, often after concentration by sedimentation/flotation or filtration techniques. The eggs are sufficiently characteristic to facilitate specific diagnosis. On occasion, microscopy of rectal biopsies has been used to diagnose S. haematobium infections. Immunoserological tests have been developed to detect host antibodies against infection but they have experienced cross-reactivity problems and cannot discriminate between previous and active infection. More recently, molecular techniques have been used to detect parasite antigens or DNA in host samples; some tests showing good correlations with parasite burdens.

Treatment and control: The drug of choice for the treatment of all Schistosoma spp. is praziquantel, a single oral dose being very effective, with low toxicity and good tolerance, even in severe clinical cases. Nitridazole and metrifonate are effective against S. haematobium, and oxamniquine against S. mansoni, but they have mild side-effects. While timely treatment is effective, cured individuals rapidly become re-infected in endemic areas. Various control programmes have therefore been developed based on mass chemotherapy in conjunction with preventive measures, including improved sanitation, snail vector control, modifying habitats and farming practices, and public education campaigns. Water contamination can be reduced by preventing the ingress of parasite eggs as well as curtailing the asexual amplification cycle in snail hosts. The provision and use of latrines contains sources of infection, and modern biocomposting toilets appear to be effective in killing parasite eggs when used properly. Snail populations may be reduced by the strategic use of molluscicides (niclosamide or copper sulphate), draining marshes and swamps, and clearing channels of vegetation. Irrigation practices can be modified to avoid long-standing still waters, and different or improved crops can be used which are less dependent on lengthy immersion in water. In endemic areas, farmers (and visitors) need to be aware of the dangers of immersion in potentially contaminated waters. Considerable resources have been devoted to the development of cellular, subcellular and recombinant vaccines, and promising results have been obtained with animal models of disease.