Schistosomiasis

Schistosomiasis /ˌʃistəsɵˈmaɪəsəs/ (also known as bilharzia, snail fever, and Katayama fever) is a disease caused by parasitic worms of the Schistosoma type. It may infect the urinary tract or intestines. Symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine. In those who have been infected a long time, liver damage, kidney failure, infertility, or bladder cancer may occur. In children it may cause poor growth and learning difficulty.

The disease is spread by contact with water that contains the parasites. These parasites are released from freshwater snails that have been infected. The disease is especially common among children in developing countries as they are more likely to play in infected water. Other high risk groups include farmers, fishermen, and people using infected water for their daily chores. It belongs to the group of helminth infections. Diagnosis is by finding the eggs of the parasite in a person's urine or stool. It can also be confirmed by finding antibodies against the disease in the blood.

Methods to prevent the disease include improving access to clean water and reducing the number of snails. In areas where the disease is common entire groups may be treated all at once and yearly with the medication praziquantel. This is done to decrease the number of people infected and therefore decrease the spread of the disease. Praziquantel is also the treatment recommended by the World Health Organization for those who are known to be infected.

Schistosomiasis affects almost 210 million people worldwide, and an estimated 12,000 to 200,000 people die from it a year. The disease is most commonly found in Africa, as well as Asia and South America. Around 700 million people, in more than 70 countries, live in areas where the disease is common. Schistosomiasis is second only to malaria, as a parasitic disease with the greatest economic impact. From ancient times to the early 20th century, schistosomiasis' symptom of blood in the urine was seen as a male version of menstruation in Egypt and was thus viewed as a rite of passage for boys, even being linked to increased fertility. It is classified as a neglected tropical disease.

Classification

Species of Schistosoma that can infect humans:

• Schistosoma mansoni (ICD-10 B65.1) and Schistosoma intercalatum (B65.8) cause intestinal schistosomiasis
• Schistosoma haematobium (B65.0) causes urinary schistosomiasis
• Schistosoma japonicum (B65.2) and Schistosoma mekongi (B65.8) cause Asian intestinal schistosomiasis

Avian schistosomiasis species cause swimmer's itch and clam digger itch

Species of Schistosoma that can infect other animals:

S. bovis â€" normally infects cattle, sheep and goats in Africa, parts of Southern Europe and the Middle East
S. mattheei â€" normally infects cattle, sheep and goats in Central and Southern Africa
S. margrebowiei â€" normally infects antelope, buffalo and waterbuck in Southern and Central Africa
S. curassoni â€" normally infects domestic ruminants in West Africa
S. rodhaini â€" normally infects rodents and carnivores in parts of Central Africa

Signs and symptoms

Above all, schistosomiasis is a chronic disease. Many infections are subclinically symptomatic, with mild anemia and malnutrition being common in endemic areas. Acute schistosomiasis (Katayama's fever) may occur weeks after the initial infection, especially by S. mansoni and S. japonicum. Manifestations include:

• Abdominal pain
• Cough
• Diarrhea
• Eosinophilia â€" extremely high eosinophil granulocyte (white blood cell) count.
• Fever
• Fatigue
• Hepatosplenomegaly â€" the enlargement of both the liver and the spleen.
  • Hepatic schistosomiasis is the second most common cause of esophageal varices worldwide.
• Genital sores â€" lesions that increase vulnerability to HIV infection. Lesions caused by schistosomiasis may continue to be a problem after control of the schistosomiasis infection itself. Early treatment, especially of children, which is relatively inexpensive, prevents formation of the sores.
• Skin symptoms: At the start of infection, mild itching and a papular dermatitis of the feet and other parts after swimming in polluted streams containing cercariae.

Occasionally central nervous system lesions occur: cerebral granulomatous disease may be caused by ectopic S. japonicum eggs in the brain, and granulomatous lesions around ectopic eggs in the spinal cord from S. mansoni and S. haematobium infections may result in a transverse myelitis with flaccid paraplegia.

Continuing infection may cause granulomatous reactions and fibrosis in the affected organs, which may result in manifestations that include:

• Colonic polyposis with bloody diarrhea (Schistosoma mansoni mostly);
• Portal hypertension with hematemesis and splenomegaly (S. mansoni, S. japonicum);
• Cystitis and ureteritis (S. haematobium) with hematuria, which can progress to bladder cancer;
• Pulmonary hypertension (S. mansoni, S. japonicum, more rarely S. haematobium);
• Glomerulonephritis;
• and central nervous system lesions.

Bladder cancer diagnosis and mortality are generally elevated in affected areas.

Pathophysiology

Life cycle

Schistosomes have a typical trematode vertebrate-invertebrate lifecycle, with humans being the definitive host. Infections by this parasitic worm is in a family of diseases known as helminthiases.

Snails

The life cycles of all five human schistosomes are broadly similar: parasite eggs are released into the environment from infected individuals, hatching on contact with fresh water to release the free-swimming miracidium. Miracidia infect freshwater snails by penetrating the snail's foot. After infection, close to the site of penetration, the miracidium transforms into a primary (mother) sporocyst. Germ cells within the primary sporocyst will then begin dividing to produce secondary (daughter) sporocysts, which migrate to the snail's hepatopancreas. Once at the hepatopancreas, germ cells within the secondary sporocyst begin to divide again, this time producing thousands of new parasites, known as cercariae, which are the larvae capable of infecting mammals.

Cercariae emerge daily from the snail host in a circadian rhythm, dependent on ambient temperature and light. Young cercariae are highly mobile, alternating between vigorous upward movement and sinking to maintain their position in the water. Cercarial activity is particularly stimulated by water turbulence, by shadows and by chemicals found on human skin.

The most common way of getting schistosomiasis in developing countries is by wading or swimming in lakes, ponds and other bodies of water that are infested with the snails (usually of the genera Biomphalaria, Bulinus, or Oncomelania) that are the natural reservoirs of the Schistosoma pathogen.

Humans

Penetration of the human skin occurs after the cercaria have attached to and explored the skin. The parasite secretes enzymes that break down the skin's protein to enable penetration of the cercarial head through the skin. As the cercaria penetrates the skin it transforms into a migrating schistosomulum stage.

The newly transformed schistosomulum may remain in the skin for two days before locating a post-capillary venule; from here the schistosomulum travels to the lungs where it undergoes further developmental changes necessary for subsequent migration to the liver. Eight to ten days after penetration of the skin, the parasite migrates to the liver sinusoids. S. japonicum migrates more quickly than S. mansoni, and usually reaches the liver within eight days of penetration. Juvenile S. mansoni and S. japonicum worms develop an oral sucker after arriving at the liver, and it is during this period that the parasite begins to feed on red blood cells. The nearly-mature worms pair, with the longer female worm residing in the gynaecophoric channel of the shorter male. Adult worms are about 10 mm long. Worm pairs of S. mansoni and S. japonicum relocate to the mesenteric or rectal veins. S. haematobium schistosomula ultimately migrate from the liver to the perivesical venous plexus of the bladder, ureters, and kidneys through the hemorrhoidal plexus.

Parasites reach maturity in six to eight weeks, at which time they begin to produce eggs. Adult S. mansoni pairs residing in the mesenteric vessels may produce up to 300 eggs per day during their reproductive lives. S. japonicum may produce up to 3,000 eggs per day. Many of the eggs pass through the walls of the blood vessels, and through the intestinal wall, to be passed out of the body in feces. S. haematobium eggs pass through the ureteral or bladder wall and into the urine. Only mature eggs are capable of crossing into the digestive tract, possibly through the release of proteolytic enzymes, but also as a function of host immune response, which fosters local tissue ulceration. Up to half the eggs released by the worm pairs become trapped in the mesenteric veins, or will be washed back into the liver, where they will become lodged. Worm pairs can live in the body for an average of four and a half years, but may persist up to twenty years.

Trapped eggs mature normally, secreting antigens that elicit a vigorous immune response. The eggs themselves do not damage the body. Rather it is the cellular infiltration resultant from the immune response that causes the pathology classically associated with schistosomiasis.

Diagnosis

Contemporary diagnosis involves detection of parasitic antigens by ELISA; all that is required from the patient is a blood sample. This screening method is highly effective. Microscopic identification of eggs in stool or, less commonly, the urine is another way of arriving at a positive diagnosis. For the measurement of eggs in the feces of presenting patients the scientific unit used is eggs per gram (epg). Stool examination should be performed when infection with S. mansoni or S. japonicum is suspected, and urine examination should be performed if S. haematobium is suspected.

Eggs can be present in the stool in infections with all Schistosoma species. The examination can be performed on a simple smear (1 to 2 mg of fecal material). Since eggs may be passed intermittently or in small amounts, their detection will be enhanced by repeated examinations and/or concentration procedures (such as the formalin-ethyl acetate technique). In addition, for field surveys and investigational purposes, the egg output can be quantified by using the Kato technique (20 to 50 mg of fecal material) or the Ritchie technique.

Eggs can be found in the urine in infections with S. japonicum and with S. intercalatum (recommended time for collection: between noon and 3 p.m.) Detection will be enhanced by centrifugation and examination of the sediment. Quantification is possible by using filtration through a nucleopore membrane of a standard volume of urine followed by egg counts on the membrane. Investigation of S. haematobium should also include a pelvic x-ray as bladder wall calcification is highly characteristic of chronic infection.

Recently a field evaluation of a novel handheld microscope was undertaken in Uganda for the diagnosis of intestinal schistosomiasis by a team led by Russell Stothard from the Natural History Museum of London, working with the Schistosomiasis Control Initiative, London.

Tissue biopsy (rectal biopsy for all species and biopsy of the bladder for S. haematobium) may demonstrate eggs when stool or urine examinations are negative.

The eggs of S. haematobium are ellipsoidal with a terminal spine, S. mansoni eggs are also ellipsoidal but with a lateral spine, S. japonicum eggs are spheroidal with a small knob.

Antibody detection can be useful in both clinical management and for epidemiologic surveys.

Prevention

A few countries have eradicated the disease, and many more are working toward it. The World Health Organization is promoting these efforts. In some cases, urbanization, pollution, and/or consequent destruction of snail habitat has reduced exposure, with a subsequent decrease in new infections.

Snails

Prevention is best accomplished by eliminating the water-dwelling snails that are the natural reservoir of the disease. Acrolein, copper sulfate, and niclosamide can be used for this purpose. Recent studies have suggested that snail populations can be controlled by the introduction of, or augmentation of existing, crayfish populations.

For many years from the 1950s onwards, vast dams and irrigation schemes were constructed, causing a massive rise in water-borne infections from schistosomiasis. The detailed specifications laid out in various UN documents since the 1950s could have minimized this problem. Irrigation schemes can be designed to make it hard for the snails to colonize the water, and to reduce the contact with the local population.

This has been cited as a classic case of the relevance paradox because guidelines on how to design these schemes to minimise the spread of the disease had been published years before, but the designers were unaware of them.

Treatment

Schistosomiasis is treatable using a single dose of the drug praziquantel by mouth annually.

The World Health Organization has developed guidelines for community treatment based on the impact the disease has on children in villages in which it is common:

• When a village reports more than 50 percent of children have blood in their urine, everyone in the village receives treatment.
• When 20 to 50 percent of children have bloody urine, only school-age children are treated.
• When fewer than 20 percent of children have symptoms, mass treatment is not implemented.

Other possible treatments include a combination of praziquantel with metrifonate, artesunate or mefloquine. A Cochrane review found tentative evidence that when used alone metrifonate was as effective as praziquantel.

Another agent, mefloquine, which has previously been used to treat malaria, was recognised in 2008â€"2009 to be effective against schistosoma. Mefloquine may be used in combination with praziquantel or artemisinins. Its mechanism of action is not known but it causes extensive and severe morphological, histopathological, and ultrastructural damage to adult and juvenile schistosomes, particularly, the worm tegument, musculature, gut, and vitelline glands of female worms.

Epidemiology

The disease is found in tropical countries in Africa, the Caribbean, eastern South America, Southeast Asia and in the Middle East. Schistosoma mansoni is found in parts of South America and the Caribbean, Africa, and the Middle East; Schistosoma haematobium in Africa and the Middle East; and Schistosoma japonicum in the Far East. Schistosoma mekongi and Schistosoma intercalatum are found locally in Southeast Asia and central West Africa, respectively.

The disease is common in about 75 developing countries and mainly affects people living in rural agricultural and peri-urban areas.

Infection estimates

In 2010, approximately 238 million people were infected with schistosomiasis, 85% of whom live in Africa. An earlier estimate from 2006 had put the figure at 200 million people infected. In many of the affected areas, schistosomiasis infects a large proportion of children under 14 years of age. An estimated 600 to 700 million people worldwide are at risk from the disease because they live in countries where the organism is common. In 2012, 249 million people were in need of treatment to prevent the disease. This likely makes its the most common parasitic infection with malaria second and causing about 207 million cases in 2013.

Deaths

Estimates regarding the number of deaths vary. Worldwide in 2010 the Global Burden of Disease estimated 12,000 direct deaths while the World Health Organization (WHO) estimates more than 200,000 people die related to schistosomiasis yearly. Another 20 million have severe consequences from the disease. It is the most deadly of the neglected tropical diseases.

History

Schistosomiasis is known as bilharzia or bilharziosis in many countries, after German physician Theodor Bilharz, who first described the cause of urinary schistosomiasis in 1851.

The first doctor who described the entire disease cycle was Brazilian parasitologist Pirajá da Silva in 1908. The first known case of infection was discovered in 2014, it belongs to a child who lived 6,200 years ago.

It was a common cause of death for Ancient Egyptians in the Greco-Roman Period.

Society and culture

Schistosomiasis is endemic in Egypt, exacerbated by the country's dam and irrigation projects along the Nile. From the late 1950s through the early 1980s, infected villagers were treated with repeated injections of tartar emetic. Epidemiological evidence suggests that this campaign unintentionally contributed to the spread of hepatitis C via unclean needles. Egypt has the world's highest hepatitis C infection rate, and the infection rates in various regions of the country closely track the timing and intensity of the anti-schistosomiasis campaign.

Schistosomiasis was mentioned in an episode of the television sitcom WKRP in Cincinnati. In the episode "Frog Story" from season 3, Dr. Johnny Fever becomes concerned that he may have schistosomiasis. Among human parasitic diseases, schistosomiasis ranks second behind malaria in terms of socio-economic and public health importance in tropical and subtropical areas.

Research

As with other major parasitic diseases, there is ongoing and extensive research into developing a schistosomiasis vaccine that will prevent the parasite from completing its life cycle in humans. In 2009, Eurogentec Biologics developed a vaccine against bilharziosis in partnership with INSERM and researchers from the Pasteur Institute.

The Bill & Melinda Gates Foundation has recently funded an operational research program â€" the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to answer strategic questions about how to move forward with schistosomiasis control and elimination. The focus of SCORE is on development of tools and evaluation of strategies for use in mass drug administration campaigns.

Mirazid, an Egyptian drug made from myrrh, was under investigation for oral treatment of the disease up until 2005. The efficacy of praziquantel was proven to be about eight times than that of Mirazid and therefore Mirazid was not recommended as a suitable agent to control schistosomiasis.