Schistosomiasis

This article is about the disease. For the organism, see Schistosoma.

Schistosomiasis
11-year-old boy with abdominal fluid and portal hypertension due to schistosomiasis (Agusan del Sur, Philippines)
Classification and external resources
Pronunciation	/ˌʃistəsoʊˈmaɪəsəs/
Specialty	Infectious disease
ICD-10	B65
ICD-9-CM	120
MedlinePlus	001321
Patient UK	Schistosomiasis
MeSH	D012552

Schistosomiasis, also known as bilharzia, snail fever, and Katayama fever, is a disease caused by parasitic flat worms of the Schistosoma type. It may infect the urinary tract or the intestines. Signs and symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine. In those who have been infected for 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 fresh water contaminated with the parasites. These parasites are released from infected freshwater snails. The disease is especially common among children in developing countries as they are more likely to play in contaminated water. Other high risk groups include farmers, fishermen, and people using unclean water during daily living. It belongs to the group of helminth infections. Diagnosis is by finding 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, the medication praziquantel is used annually to treat entire groups simultaneously. This is done to decrease the number of people infected and, consequently, the spread of the disease. Praziquantel is also the treatment recommended by the World Health Organization (WHO) for those who are known to be infected.

According to a report published in 2012, schistosomiasis affects almost 210 million people worldwide. An estimated 12,000 to 200,000 people die from it annually. 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. In tropical countries, schistosomiasis is second only to malaria among parasitic diseases with the greatest economic impact. In 2011, the Centers for Disease Control and Prevention listed schistosomiasis 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.

Species of Schistosoma that can infect other animals:

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

Signs and symptoms

Skin blisters on the forearm, created by the entrance of Schistosoma parasite

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 — extremely high eosinophil granulocyte (white blood cell) count.
• Fever
• Fatigue
• Hepatosplenomegaly — the enlargement of both the liver and the spleen.
  • Hepatic schistosomiasis is the second most common cause of esophageal varices worldwide.
• Genital sores — 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 fresh water containing cercariae.

Central nervous system lesions occur occasionally: 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.

Calcification of the bladder wall on a plain x-ray image of the pelvis, in a 44-year-old sub-Saharan man. This is due to urinary schistosomiasis.

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

• Colonic polyposis with bloody diarrhea (S. 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

Schistosoma 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.

Photomicrography of bladder in S. hematobium infection, showing clusters of the parasite eggs with intense eosinophilia.

Diagnosis

High powered detailed micrograph of Schistosoma parasite eggs in human bladder tissue.

S. japonicum eggs in hepatic portal tract.

Microscopic identification of eggs in stool or urine is the most practical method for diagnosis. 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. In addition, for field surveys and investigational purposes, the egg output can be quantified by using the Kato-Katz technique (20 to 50 mg of fecal material) or the Ritchie technique. Eggs can be found in the urine in infections with S. haematobium (recommended time for collection: between noon and 3 PM) and with S. japonicum. Quantification is possible by using filtration through a nucleopore filter membrane of a standard volume of urine followed by egg counts on the membrane. 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.

Antibody detection

Antibody detection can be useful to indicate schistosome infection in people who have traveled to areas were schistosomiasis is common and in whom eggs cannot be demonstrated in fecal or urine specimens. Test sensitivity and specificity vary widely among the many tests reported for the serologic diagnosis of schistosomiasis and are dependent on both the type of antigen preparations used (crude, purified, adult worm, egg, cercarial) and the test procedure.

At CDC, a combination of tests with purified adult worm antigens are used for antibody detection. All serum specimens are tested by FAST-ELISA using Schistosoma mansoni adult microsomal antigen (MAMA). A positive reaction (greater than 9 units/µl serum) indicates infection with Schistosoma species. Sensitivity for S. mansoni infection is 99%, 95% for Schistosoma haematobium infection, and <50% for Schistosoma japonicuminfection. Specificity of this assay for detecting schistosome infection is 99%. Because test sensitivity with the FAST-ELISA is reduced for species other than S. mansoni, immunoblots of the species appropriate to the patient's travel history are also tested to ensure detection of S. haematobium and S. japonicum infections. Immunoblots with adult worm microsomal antigens are species-specific and so a positive reaction indicates the infecting species. The presence of antibody is indicative only of schistosome infection at some time and cannot be correlated with clinical status, worm burden, egg production, or prognosis. Were a person has traveled can help determine what Schistosoma species to test for by immunoblot.

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.

Prevention

Many countries are working towards eradicating the disease. The WHO is promoting these efforts. In some cases, urbanization, pollution, and consequent destruction of snail habitat have reduced exposure, with a subsequent decrease in new infections. Furthermore, the drug praziquantel is used for prevention in high-risk populations living in areas were the disease is common.

A 2014 review found tentative evidence that increasing access to clean water and sanitation reduces schistosome infection.

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.

While 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

See also: Schistosomicide

Ethiopian children treated for schistosoma mansoni

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

The WHO 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 and prevent malaria, was recognised in 2008–2009 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

Disability-adjusted life year for schistosomiasis per 100,000 inhabitants.

  no data

  less than 50

  50–75

  75–100

  100–150

  150–200

  200–250

  250–300

  300–350

  350–400

  400–450

  450–500

  more than 500

The disease is found in tropical countries in Africa, the Caribbean, eastern South America, Southeast Asia, and 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 percent 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 it the most common parasitic infection with malaria second and causing about 207 million cases in 2013.

Schistosoma haematobium, the infectious agent responsible for urogenital schistosomiasis, infects over 112 million people annually in Sub-Saharan Africa alone. It is responsible for 32 million cases of dysuria, 10 million cases of hydronephrosis, and 150,000 deaths from renal failure annually, making Schistosoma haematobium the world’s deadliest schistosome.

Deaths

Estimates regarding the number of deaths vary. Worldwide in 2010 the Global Burden of Disease estimated 12,000 direct deaths while the 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 physician 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. 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.

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 — 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.

External links

• Schistosomiasis at DMOZ
• UNHCO site on Schistosomiasis
• River of Hope — documentary about the rise of schistosomiasis along the Senegal river (video, 47 mins)
• Schistosomiasis information for travellers from IAMAT (International Association for Medical Assistance to Travellers)