Schistosomiasis

Brijesh Singh Yadav brijeshbioinfo@gmail.com Disease Type: Parasitic Disease Common Name: Bilharzia, Bilharziosis or Snail fever Causative Agent: Several species of fluke of the genus Schistosoma

Disease Discription:
Schistosomiasisis a parasitic disease caused by several species of fluke of the genus Schistosoma. It is most commonly found in Asia, Africa, and South America, especially in areas with water that is contaminated with freshwater snails, which may carry the parasite. The disease affects many people in developing countries, particularly children who may acquire the disease by swimming or playing in infected water.[1] Although it has a low mortality rate, schistosomiasis often is a chronic illness that can damage internal organs and, in children, impair growth and cognitive development.[1] The urinary form of schistosomiasis is associated with increased risks for bladder cancer in adults.[1]Schistosomiasis is the second-most socioeconomically devastating disease after malaria.[1]

Fig.Schistosome dermatitis

Infected Boy

Schistosomiasis

Types of Disease:
There are five species of flatworms that cause schistosomiasis. Each causes a different clinical presentation of the disease. Schistosomiasis may localize in different parts of the body, and its localization determines its particular clinical profile.

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

Causes of Disease:
Infection is the most common cause Viral (e.g., influenza, HIV, hepatitis, herpes simplex encephalitis, mononucleosis, adenovirus) Bacterial (e.g., pneumonia, endocarditis, tuberculosis, meningitis, pyelonephritis, appendicitis, cholecystitis, cellulitis) Lyme disease Malaria Syphilis Tularemia Intra-abdominal abscess

Malignancy Lymphoma (Hodgkin's and non-Hodgkin's) Lymphoproliferative disorders Renal cell carcinoma Leukemia Hepatocellular carcinoma Rheumatologic disorders Temporal arteritis/giant cell arteritis Adult-onset Still's disease Systemic lupus erythematosus Sarcoidosis Rheumatoid arthritis Drug fever Often temporally associated with the initiation of a new medicine Often associated with a rash (biopsy reveals leukocytoclastic vasculitis) Eosinophilia is common

Pulmonary embolism Mild fever is often present Other findings of thromboembolic disease (e.g., leg swelling, dyspnea) may be present

Osteomyelitis Occult abscess Malignant hypothermia

Risk Factors:
The list of risk factors mentioned for Schistosomiasis in various sources includes:

Water snails

Drinking contaminated water Bathing in contaminated water Swimming in contaminated water Urine Feces Sewage International travel Middle East Africa Asia Central America South America

Causative Agent: Pathogen Name: Several species of fluke of the genus Schistosoma. Pathogen Description:
A genus of trematodes, Schistosoma spp., commonly known as blood-flukes and bilharzia, cause the most significant infection of humans by flatworms (schistosomiasis) and are considered by the World Health Organization as second in importance only to malaria, with hundreds of millions infected worldwide. Adult worms parasitize mesenteric blood vessels. Eggs are passed through urine or feces to fresh water, where larval stages can infect a new host by penetrating the skin. There are four species of schistosome which are infective to humans:

Schistosoma mansoni, found in Africa, Brazil, Venezuela, Suriname, the lesser Antilles, Puerto Rico, and the Dominican Republic. It is also known as Manson's blood fluke or swamp fever. Freshwater snails of the Biomphalaria genus are an important host for this trematode. S. japonicum whose common name is simply blood fluke is found widely spread in Eastern Asia and the southwestern Pacific region. In Taiwan this species only affects animals, not humans. Freshwater snails of the Oncomelania genus are an important host for S. japonicum.

S. mekongi is related to S. japonicum and affects both superior and inferior mesenteric veins. S. mekongi differs in that it has smaller eggs, a different intermediate host, and longer prepatent period in the mammalian host. S. haematobium, commonly referred to as the bladder fluke, originally found in Africa, the Near East, and the Mediterranean basin, was introduced into India during World War II. Freshwater snails of the Bulinus genus are an important host for this parasite.

S. indicum, S. nasale, S. leiperi are all parasites of ruminants.

Taxonoimic Classification:
Kingdom: Phylum: Class: Subclass: Order: Family: Genus: Animalia Platyhelminthes Trematoda Digenea Strigeidida Schistosomatidae Schistosoma

Pathogenic speices: S. mansoni, S. japonicum, S. mekongi, S. intercalatum, S. haematobium, S. indicum, S. nasale, S. leiperi ,S. malayensis, S. rodhaini

S. japonicum

Schistsoma mansoni

Morphology and toxin production:

Adult schistosomes share all the fundamental features of the digenea. They have a basic bilateral symmetry, oral and ventral suckers, a body covering of a syncytial tegument, a blind-ending digestive system consisting of mouth, oesophagus and bifurcated caeca; the area between the tegument and alimentary canal filled with a loose network of mesoderm cells, and an excretory or osmoregulatory system based on flame cells. Adult worms tend

to be 10-20 mm long and use globins from their hosts' hemoglobin for their own circulatory system. Unlike other trematodes, the schistosomes are dioecious - i.e., the sexes are separate. The two sexes display a strong degree of sexual dimorphism, and the male is considerably larger than the female. The male surrounds the female and encloses her within his gynacophoric canal for the entire adult lives of the worms, where they reproduce sexually.

Fig.Schistosoma (male & female)

History:
The first doctor who described the entire disease cycle was Piraj da Silva in 1908. Schistosomiasis is known as bilharzia or bilharziosis in many countries, after Theodor Bilharz, who first described the cause of urinary schistosomiasis in 1851.

Epidemiology:

The disease is endemic to 74 countries, affecting an estimated 200 million people, half of whom live in Africa.[1] 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. The most common way of getting schistosomiasis in developing countries is by wading or swimming in lakes, ponds and other bodies of water which are infested with the snails (usually of the Biomphalaria, Bulinus, or Oncomelania genus) that are the natural reservoirs of the Schistosoma pathogen.

Disease Host: Disease Transmission:

Life Cycle: Schistosomes have a typical trematode vertebrate-invertebrate lifecycle, with humans being the definitive host. 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 fresh-water 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. 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 2 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 8 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 3000 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 faeces. 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 20 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.[4]

Fig.Life Cycle of pathogen

Signs and symptoms of disease:

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 - extremely high eosinophil granulocyte count. Fever Fatigue Hepatosplenomegaly - the enlargement of both the liver and the spleen.

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.

Diagnosis:
Microscopic identification of eggs in stool or urine is the most practical method for diagnosis. The stool exam is the more common of the two. For the measurement of eggs in the feces of presenting patients the scientific unit used is epg or eggs per gram. 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-Katz 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 PM). 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 xray as bladder wall calcificaition 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 Dr. Russell Stothard who heads the Schistosomiasis Control Iniative at the Natural History Museum, London. His report abstract may be found here: [1]

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

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

Treatment:
Schistosomiasis is readily treated using a single oral dose of the drug praziquantel annually.[4] As with other major parasitic diseases, there is ongoing and extensive research into developing a vaccine that will prevent the parasite from completing its life cycle in humans. The World Health Organization has developed guidelines for community treatment schistosomiasis based on the impact the disease has on children in endemic villages:[4] When a village reports more than 50 percent of children have blood in their urine, everyone in the village receives treatment.[4] When 20 to 50 percent of children have bloody urine, only schoolage children are treated.[4] When less than 20 percent of children have symptoms, mass treatment is not implemented.[4]

Antimony has been used in the past to treat the disease. In low doses, this toxic metalloid bonds to sulfur atoms in enzymes used by the parasite and kills it without harming the

host. This treatment is not referred to in present-day peer-review scholarship; Praziquantel is universally used. Outside of the US, there is a second drug available for treating Schistosoma mansoni (exclusively) called Oxamniquine. Mirazid, a new Egyptian drug, is under investigation for oral treatment of the disease. Experiments have shown medicinal Castor oil as an oral anti-penetration agent to prevent Schistosomiasis and that praziquantel's effectiveness depended upon the vehicle used to administer the drug (e.g., Cremophor / Castor oil).[5] Additionally Dr Chidzere of Zimbabwe researched the Gopo Berry (Phytolacca dodecandra) during the 1980's and found that the Gopo Berry could be used in the control of the freshwater snails which carry the bilharzia disease (Schistosomiasis parasite). Dr Chidzere in his interview to Andrew Blake (1989) reported concerns of muti-national chemical companies keen to rubbish the Gopu Berry alternative for snail control [6]. Reputedly Gopo Berries from hotter Ethiopia climates yield the best results. Later studies were between 1993-95 by the Danish Research Network for international health. [7][8]

Prevention of disease:
No vaccine is available, nor are any drugs recommended as chemoprophylactic agents at this time. Because there is no practical way for the traveler to distinguish infested from noninfested water, travelers should be advised to avoid wading, swimming or other contact with freshwater in disease-endemic countries. Untreated piped water coming directly from canals, lakes, rivers, streams or springs may contain cercariae, but heating bathing water to 50 C (122 F) for 5 minutes or filtering water with fine-mesh filters can eliminate the risk of infection. If such measures are not feasible, travelers should be advised to allow bathing water to stand for 2 days, because cercariae rarely remain infective longer than 24 hours. Swimming in adequately chlorinated swimming pools is virtually always safe, even in disease-endemic countries. Vigorous towel-drying after accidental exposure to water has been suggested as a way to remove cercariae before they can penetrate the skin; however, this may prevent only some infections and should not be recommended to travelers as a preventive measure. Although topical application of the insect repellent DEET can block penetrating cercariae, the effect is short lived and cannot reliably prevent infection .[2] Upon return from foreign travel, persons who may have been exposed to schistosomeinfested freshwater should be advised to undergo screening tests. Because serologic tests are more sensitive than microscopic examination of stool and urine for eggs, previously uninfected but potentially exposed travelers should be tested for antibodies to schistosomes if microscopic examination of stool and urine for eggs is negative or not available. CDC performs a screening ELISA that is 99%, 90%, and 50% sensitive for Schistosoma mansoni, S. haematobium, and S. japonicum, respectively, and a confirmatory, species-specific immunoblot that is at least 95% sensitive and 99%

specific for all three species . Serologic tests performed in commercial laboratories may not be as sensitive or specific.[3] Eliminating or avoiding the snails Prevention is best accomplished by eliminating the water-dwelling snails which 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 or augmentation of existing crayfish populations; as with all ecological interventions, however, this technique must be approached with caution. Individuals can guard against schistosomiasis infection by avoiding bodies of water known or likely to harbor the carrier snails. In 1989, Aklilu Lemma and Legesse Wolde-Yohannes received the Right Livelihood Award for their research on the sapindus plant (Phytolacca dodecandra), as a preventative measure for the disease by controlling the snail.

Geographical Distribution: The disease is found in tropical countries in Africa,

Caribbean, eastern South America, east Asia and in the Middle East. Schistosoma 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 focally in Southeast Asia and central West Africa, respectively.

Disease Statistics:
Schistosomiasis is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that Schistosomiasis, or a subtype of Schistosomiasis, affects less than 200,000 people in the US population. Ophanet, who are a consortium of European partners, currently defines a condition rare when if affects 1 person per 2,000. They list Schistosomiasis as a "rare disease".

Hospitalization statistics for Schistosomiasis:

The following are statistics from various sources about hospitalizations and Schistosomiasis: 0.0005% (59) of hospital consultant episodes were for schistosomiasis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 98% of hospital consultant episodes for schistosomiasis required hospital admission in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 73% of hospital consultant episodes for schistosomiasis were for men in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 27% of hospital consultant episodes for schistosomiasis were for women in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 9% of hospital consultant episodes for schistosomiasis required emergency hospital admission in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 2.7 days was the mean length of stay in hospitals for schistosomiasis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 1 days was the median length of stay in hospitals for schistosomiasis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 31 was the mean age of patients hospitalised for schistosomiasis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 86% of hospital consultant episodes for schistosomiasis occurred in 15-59 year olds in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 0% of hospital consultant episodes for schistosomiasis occurred in people over 75 in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 54% of hospital consultant episodes for schistosomiasis were single day episodes in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03) 0.0001% (72) of hospital bed days were for schistosomiasis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

Refrence:
1. The Carter Center, "Schistosomiasis Control Program", <http://www.cartercenter.org/health/schistosomiasis/index.html>. Retrieved on 17 July 2008. 2. Corachan M. Schistosomiasis and international travel. Clin Infect Dis. 2002;35:446-50. Jordan P, Webbe G, Sturrock RF, eds. Human schistosomiasis. Wallingford: CAB International; 1993. 3. Tsang VC, Wilkins PP. Immunodiagnosis of schistosomiasis. Screen with FASTELISA and confirm with immunoblot. Clin Lab Med. 1991;11:1029-39. 4. The Carter Center, "How is Schistosomiasis Treated?", 5.
6. <http://www.cartercenter.org/health/schistosomiasis/treatment.html>. Retrieved on 17 July 2008 Salafsky B, Fusco AC, Li LH, Mueller J, Ellenberger B (October 1989). "Schistosoma mansoni: experimental chemoprophylaxis in mice using oral anti-penetration agents". Exp. Parasitol. 69 (3): 26371. PMID 2507345. The Gopu Berry p33. Part 4 School Journal number.2 1989 Dept of Education Wellington N.Z Chihaka abstract Mlgaard P, Chihaka A, Lemmich E, et al (December 2000). "Biodegradability of the molluscicidal saponins of Phytolacca dodecandra". Regul. Toxicol. Pharmacol. 32 (3): 24855. doi:10.1006/rtph.2000.1390. PMID 11162718

7. 8.