Schistosomiasis

Schistosomiasis, also known as snail fever and bilharzia,[9] is a disease caused by parasitic flatworms called schistosomes.[5] The urinary tract or the intestines may be infected.[5] Symptoms include abdominal pain, diarrhea, bloody stool, or blood in the urine.[5] Those who have been infected for a long time may experience liver damage, kidney failure, infertility, or bladder cancer.[5] In children, it may cause poor growth and learning difficulty.[5]

This article is about the disease. For the organism, see Schistosoma.
Schistosomiasis
Other namesBilharzia, snail fever, Katayama fever[1][2]
11-year-old boy with abdominal fluid and portal hypertension due to schistosomiasis (Agusan del Sur, Philippines)
Pronunciation
  • /ˌʃɪstəsəˈmaɪəsɪs, -toʊ-, -soʊ-/[3][4]
SpecialtyInfectious disease
SymptomsAbdominal pain, diarrhea, bloody stool, blood in the urine[5]
ComplicationsLiver damage, kidney failure, infertility, bladder cancer[5]
CausesSchistosomes from freshwater snails[5]
Diagnostic methodFinding eggs of the parasite in urine or stool, antibodies in blood[5]
PreventionAccess to clean water[5]
MedicationPraziquantel[5]
Frequency252 million (2015)[6]
Deaths4,400–200,000[7][8]

The disease is spread by contact with fresh water contaminated with the parasites.[5] These parasites are released from infected freshwater snails.[5] The disease is especially common among children in developing countries, as they are more likely to play in contaminated water.[5] Other high-risk groups include farmers, fishermen, and people using unclean water during daily living.[5] It belongs to the group of helminth infections.[10] Diagnosis is by finding eggs of the parasite in a person's urine or stool.[5] It can also be confirmed by finding antibodies against the disease in the blood.[5]

Methods to prevent the disease include improving access to clean water and reducing the number of snails.[5] In areas where the disease is common, the medication praziquantel may be given once a year to the entire group.[5] This is done to decrease the number of people infected, and consequently, the spread of the disease.[5] Praziquantel is also the treatment recommended by the World Health Organization for those who are known to be infected.[5]

Schistosomiasis affected about 252 million people worldwide in 2015.[6] An estimated 4,400 to 200,000 people die from it each year.[7][8] The disease is most commonly found in Africa, Asia, and South America.[5] Around 700 million people, in more than 70 countries, live in areas where the disease is common.[7][11] In tropical countries, schistosomiasis is second only to malaria among parasitic diseases with the greatest economic impact.[12] Schistosomiasis is listed as a neglected tropical disease.[13]

Signs and symptoms
Skin blisters on the forearm, created by the entrance of Schistosoma parasites

Many individuals do not experience symptoms. If symptoms do appear, they usually take 4–6 weeks from the time of infection. The first symptom of the disease may be a general feeling of illness. Within 12 hours of infection, an individual may complain of a tingling sensation or light rash, commonly referred to as "swimmer's itch", due to irritation at the point of entrance. The rash that may develop can mimic scabies and other types of rashes. Other symptoms can occur 2–10 weeks later and can include fever, aching, a cough, diarrhea, chills, or gland enlargement. These symptoms can also be related to avian schistosomiasis, which does not cause any further symptoms in humans.

The manifestations of schistosomal infection vary over time as the cercariae, and later adult worms and their eggs, migrate through the body.[14] If eggs migrate to the brain or spinal cord, seizures, paralysis, or spinal-cord inflammation are possible.[15]

Intestinal schistosomiasis

In intestinal schistosomiasis, eggs become lodged in the intestinal wall and cause an immune system reaction called a granulomatous reaction. This immune response can lead to obstruction of the colon and blood loss. The infected individual may have what appears to be a potbelly. Eggs can also become lodged in the liver, leading to high blood pressure through the liver, enlarged spleen, the buildup of fluid in the abdomen, and potentially life-threatening dilations or swollen areas in the esophagus or gastrointestinal tract that can tear and bleed profusely (esophageal varices). In rare instances, the central nervous system is affected. Individuals with chronic active schistosomiasis may not complain of typical symptoms.

Dermatitis

The first potential reaction is an itchy, papular rash[16]:432 that results from cercariae penetrating the skin, often in a person's first infection.[14] The round bumps are usually one to three centimeters across.[17] Because people living in affected areas have often been repeatedly exposed, acute reactions are more common in tourists and migrants.[18] The rash can occur between the first few hours and a week after exposure and lasts for several days.[17] A similar, more severe reaction called "swimmer's itch" reaction can also be caused by cercariae from animal trematodes that often infect birds.[14][19]

Katayama fever

Another primary condition, called Katayama fever, may also develop from infection with these worms, and it can be very difficult to recognize. Symptoms include fever, lethargy, the eruption of pale temporary bumps associated with severe itching (urticarial) rash, liver and spleen enlargement, and bronchospasm.

Acute schistosomiasis (Katayama fever) may occur weeks or months after the initial infection as a systemic reaction against migrating schistosomulae as they pass through the bloodstream through the lungs to the liver.[14] Similarly to swimmer's itch, Katayama fever is more commonly seen in people with their first infection such as migrants and tourists. It is seen, however, in native residents of China infected with S. japonicum.[20] Symptoms include:

  • Dry cough with changes on chest X-ray
  • Fever
  • Fatigue
  • Muscle aches
  • Malaise
  • Abdominal pain
  • Enlargement of both the liver and the spleen

The symptoms usually get better on their own, but a small proportion of people have persistent weight loss, diarrhea, diffuse abdominal pain, and rash.[14]

Chronic disease

In long-established disease, adult worms lay eggs that can cause inflammatory reactions. The eggs secrete proteolytic enzymes that help them migrate to the bladder and intestines to be shed. The enzymes also cause an eosinophilic inflammatory reaction when eggs get trapped in tissues or embolize to the liver, spleen, lungs, or brain.[14] The long-term manifestations are dependent on the species of schistosome, as the adult worms of different species migrate to different areas.[21] Many infections are mildly symptomatic, with anemia and malnutrition being common in endemic areas.[22]

Genitourinary disease
Calcification of the bladder wall on a plain X-ray image of the pelvis, in a 44-year-old sub-Saharan man, due to urinary schistosomiasis

The worms of S. haematobium migrate to the veins around the bladder and ureters.[21] This can lead to blood in the urine 10 to 12 weeks after infection.[14][17] Over time, fibrosis can lead to obstruction of the urinary tract, hydronephrosis, and kidney failure.[14][17] Bladder cancer diagnosis and mortality are generally elevated in affected areas; efforts to control schistosomiasis in Egypt have led to decreases in the bladder cancer rate.[17][23] The risk of bladder cancer appears to be especially high in male smokers, perhaps due to chronic irritation of the bladder lining allowing it to be exposed to carcinogens from smoking.[19][21]

In women, genitourinary disease can also include genital lesions that may lead to increased rates of HIV transmission.[17][24][25]

Gastrointestinal disease

The worms of S. mansoni and S. japonicum migrate to the veins of the gastrointestinal tract and liver.[19] Eggs in the gut wall can lead to pain, blood in the stool, and diarrhea (especially in children).[19] Severe disease can lead to narrowing of the colon or rectum.[17] Eggs also migrate to the liver leading to fibrosis in 4 to 8% of people with chronic infection, mainly those with long-term heavy infection.[19] S. mansoni infection epidemiologically overlaps with high HIV prevalence in Sub-Saharan Africa, where gastrointestinal schistosomiasis has been linked to increased HIV transmission.[24]

Central nervous system disease

Central nervous system lesions occur occasionally. Cerebral granulomatous disease may be caused by S. japonicum eggs in the brain. Communities in China affected by S. japonicum have rates of seizures eight times higher than baseline.[19] Similarly, granulomatous lesions from S. mansoni and S. haematobium eggs in the spinal cord can lead to transverse myelitis with flaccid paraplegia.[26] Cerebral granulomatous infection may also be caused by S. mansoni. In situ egg deposition following the anomalous migration of the adult worm appears to be the only mechanism by which Schistosoma can reach the central nervous system in these patients. The destructive action on the nervous tissue and the mass effect produced by a large number of eggs surrounded by multiple, large granulomas in circumscribed areas of the brain characterize the pseudotumoral form of neuroschistosomiasis and are responsible for the appearance of clinical manifestations: headache, hemiparesis, altered mental status, vertigo, visual abnormalities, seizures, and ataxia. In cases with advanced hepatosplenic and urinary schistosomiasis, the continuous embolization of eggs from the portal mesenteric system (S. mansoni) or portal mesenteric-pelvic system (S. haematobium) to the brain, results in a sparse distribution of eggs associated with scant periovular inflammatory reaction, usually with little or no clinical significance.[27]

Transmission

Infected individuals release Schistosoma eggs into water via their fecal material or urine.[28] After larvae hatch from these eggs, the larvae infect a very specific type of freshwater snail. For example, in S. haematobium and S. intercalatum it is snails of the genus Bulinus, in S. mansoni it is Biomphalaria, and in S. japonicum it is Oncomelania.[29] The Schistosoma larvae undergo the next phase of their lifecycles in these snails, spending their time reproducing and developing. Once this step has been completed, the parasite leaves the snail and enters the water column. The parasite can live in the water for only 48 hours without a mammalian host. Once a host has been found, the worm enters its blood vessels. For several weeks, the worm remains in the vessels, continuing its development into its adult phase. When maturity is reached, mating occurs and eggs are produced. Eggs enter the bladder/intestine and are excreted through urine and feces and the process repeats. If the eggs do not get excreted, they can become engrained in the body tissues and cause a variety of problems such as immune reactions and organ damage.

Humans encounter larvae of the Schistosoma parasite when they enter contaminated water while bathing, playing, swimming, washing, fishing, or walking through the water.[30][31][28]

Diagnosis
High-powered detailed micrograph of Schistosoma parasite eggs in human bladder tissue
S. japonicum eggs in hepatic portal tract

Identification of eggs in stools

Diagnosis of infection is confirmed by the identification of eggs in stools. Eggs of S. mansoni are about 140 by 60 µm in size and have a lateral spine. The diagnosis is improved through the use of the Kato technique, a semiquantitative stool examination technique. Other methods that can be used are enzyme-linked immunosorbent assay, circumoval precipitation test, and alkaline phosphatase immunoassay.[32]

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). Because eggs may be passed intermittently or in small numbers, their detection is enhanced by repeated examinations or concentration procedures, or both. 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.[33]

Identification of microhematuria in urine using urine reagent strips is more accurate than circulating antigen tests in the identification of active schistosomiasis in endemic areas.[34]

Antibody detection

Antibody detection can be useful to indicate schistosome infection in people who have traveled to areas where 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.[33]

At the U.S. Centers for Disease Control and Prevention, a combination of tests with purified adult worm antigens is used for antibody detection. All serum specimens are tested by FAST-ELISA using S. mansoni adult microsomal antigen. A positive reaction (greater than 9 units/µl serum) indicates infection with Schistosoma species. Sensitivity for S. mansoni infection is 99%, 95% for S. haematobium infection, and less than 50% for S. japonicum infection. 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, 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. Where a person has traveled can help determine which Schistosoma species to test for by immunoblot.[33]

In 2005, 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.[35]

Molecular diagnostics

Polymerase chain reaction (PCR) based testing is accurate and rapid.[36] However, it is not frequently used in countries where the disease is common due to the cost of the equipment and the technical expertise required to run the tests.[36] Using a microscope to detect eggs costs about US$0.40 per test whereas PCR is about $US 7 per test as of 2019.[37] Loop-mediated isothermal amplification are being studied as they are lower cost.[36] LAMP testing is not commercially available as of 2019.[37]

Prevention
"Schistosomes are here. People and livestock are strictly prohibited from entering the water!", a warning painted on a Yangtze levee in Honghu, Hubei, China

Many countries are working towards eradicating the disease. The World Health Organization is promoting these efforts. In some cases, urbanization, pollution, and the consequent destruction of snail habitat have reduced exposure, with a subsequent decrease in new infections. The drug praziquantel is used for prevention in high-risk populations living in areas where the disease is common.[38] The Centers for Disease Control and Prevention advises avoiding drinking or coming into contact with contaminated water in areas where schistosomiasis is common.[39]

A 2014 review found tentative evidence that increasing access to clean water and sanitation reduces schistosome infection.[40]

Snails, dams, and prawns

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 United Nations 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.[41] Even though guidelines on how to design these schemes to minimise the spread of the disease had been published years before, the designers were unaware of them.[42] The dams appear to have reduced the population of the large migratory prawn Macrobrachium. After the construction of fourteen large dams, greater increases in schistosomiasis occurred in the historical habitats of native prawns than in other areas. Further, at the 1986 Diama Dam on the Senegal River, restoring prawns upstream of the dam reduced both snail density and the human schistosomiasis reinfection rate.[43][44]

Integrated strategy in China

In China, the national strategy for schistosomiasis control has shifted three times since it was first initiated: transmission control strategy (from mid-1950s to early 1980s), morbidity control strategy (from mid-1980s to 2003), and the "new integrated strategy" (2004 to present). The morbidity control strategy focused on synchronous chemotherapy for humans and bovines and the new strategy developed in 2004 intervenes in the transmission pathway of schistosomiasis, mainly including replacement of bovines with machines, prohibition of grazing cattle in the grasslands, improving sanitation, installation of fecal-matter containers on boats, praziquantel drug therapy, snail control, and health education. A 2018 review found that the "new integrated strategy" was highly effective to reducing the rate of S. japonicum infection in both humans and the intermediate host snails and reduced the infection risk by 3–4 times relative to the conventional strategy.[45]

Treatment
See also: Schistosomicide
Ethiopian children treated for Schistosoma mansoni

Two drugs, praziquantel and oxamniquine, are available for the treatment of schistosomiasis.[46] They are considered equivalent in relation to efficacy against S. mansoni and safety.[47] Because of praziquantel's lower cost per treatment, and oxaminiquine's lack of efficacy against the urogenital form of the disease caused by S. haematobium, in general praziquantel is considered the first option for treatment.[48] The treatment objective is to cure the disease and to prevent the evolution of the acute to the chronic form of the disease. All cases of suspected schistosomiasis should be treated regardless of presentation because the adult parasite can live in the host for years.[49]

Schistosomiasis is treatable by taking by mouth a single dose of the drug praziquantel annually.[50]

The WHO has developed guidelines for community treatment based on the impact the disease has on children in villages in which it is common:[50]

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

Other possible treatments include a combination of praziquantel with metrifonate, artesunate, or mefloquine.[51] A Cochrane review found tentative evidence that when used alone, metrifonate was as effective as praziquantel.[51]

Another agent, mefloquine, which has previously been used to treat and prevent malaria, was recognised in 2008–2009 to be effective against Schistosoma.[52]

Historically, antimony potassium tartrate remained the treatment of choice for schistosomiasis until the development of praziquantel in the 1980s.[53]

Epidemiology
Deaths from schistosomiasis per million persons in 2012
  no data
  0-1
  1-2
  3-4
  5-13
  14-15
  16-18
  19-21
  22-24
  25-28
  29-40
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. S. mansoni is found in parts of South America and the Caribbean, Africa, and the Middle East; S. haematobium in Africa and the Middle East; and S. japonicum in the Far East. S. mekongi and S. intercalatum are found locally in Southeast Asia and central West Africa, respectively.

The disease is endemic in about 75 developing countries and mainly affects people living in rural agricultural and peri-urban areas.[54][55][30]

Infection estimates

In 2010, approximately 238 million people were infected with schistosomiasis, 85 percent of whom live in Africa.[56] An earlier estimate from 2006 had put the figure at 200 million people infected.[57] 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.[7][55] In 2012, 249 million people were in need of treatment to prevent the disease.[58] This likely makes it the most common parasitic infection with malaria second and causing about 207 million cases in 2013.[55][59]

S. haematobium, the infectious agent responsible for urogenital schistosomiasis, infects over 112 million people annually in Sub-Saharan Africa alone.[60] It is responsible for 32 million cases of dysuria, 10 million cases of hydronephrosis, and 150,000 deaths from kidney failure annually, making S. haematobium the world's deadliest schistosome.[60]

Deaths

Estimates regarding the number of deaths vary. Worldwide, the Global Burden of Disease Study issued in 2010 estimated 12,000 direct deaths[61] while the WHO in 2014 estimated more than 200,000 annual deaths related to schistosomiasis.[5][7] Another 20 million have severe consequences from the disease.[62] It is the most deadly of the neglected tropical diseases.[55]

History
Theodor Bilharz (1825–1862)

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.[63]

The first physician who described the entire disease cycle was the Brazilian parasitologist Pirajá da Silva in 1908.[64][65] The earliest known case of infection was discovered in 2014, belonging to a child who lived 6,200 years ago.[66]

It was a common cause of death for Egyptians in the Greco-Roman Period.[67]

In 2016 more than 200 million people needed treatment but only 88 million people were actually treated for schistosomiasis.[68]

Etymology
Main article: History of schistosomes

Schistosomiasis is named for the genus of parasitic flatworm Schistosoma, whose name means 'split body'. The name Bilharzia comes from Theodor Bilharz, a German pathologist working in Egypt in 1851 who first discovered these worms.

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.[69] 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.[70][71]

Among human parasitic diseases, schistosomiasis ranks second behind malaria in terms of socio-economic and public health importance in tropical and subtropical areas.[72]

Research

A proposed vaccine against S. haematobium infection called "Bilhvax" underwent a phase 3 clinical trial among children in Senegal: the results, reported in 2018, showed that it was not effective despite provoking some immune response.[73]Using CRISPR gene editing technology, researchers decreased the symptoms due to schistosomiasis in an animal model.[74]

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gollark: Sure?
gollark: The Pi 4 is generally better, but it needs good cooling to run at maximum power for ages and has more PSU demands.
gollark: Well, yes, it tries to power-manage, but it can cause lots of exciting problems.
gollark: You probably should anyway. The 4 is power-hungry.

See also

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