Schistosomiasis Neena Davisson March 15, 2012

Schistosomiasis is a parasitic infection Schistosomiasis is caused by a trematode helminth http://www.e-cleansing.com/parasites/schistosomiasis-schistosoma-japonicum.html

Schistosomiasis is an ancient disease http://questgarden.com/97/11/2/100224101015/process.htm Schistosome eggs have been recovered from both Chinese and Egyptian mummies

Schistosomiasis is an ancient disease Hieroglyphics also refer to the disease. in the “Papyrus Ebers” (1550 BC) appear to refer to the disease, bloody urine being frequently mentioned. Middle East Assyrian records (3000-1500 BC) http://fashioninn4us.blogspot.com/2012/02/schistosomiasis-ancient-egyptian.html

Schistosomiasis is prevalent in tropical and sub-tropical areas Schistosomiasis is endemic to Africa, and is also found in the Far East, South America, the Caribbean, and the Middle East. The worms that cause schistosomiasis are not found in the United States. http://www.ihatetaxis.com/medical/schistosomiasis

Schistosomiasis is commonly found in areas without safe water and good sanitation. At-risk groups include… Agricultural and fishing populations Image: http://blogs.worldwatch.org/nourishingtheplanet/wp-content/uploads/2010/10/lake-victoria.jpg?cda6c1

Schistosomiasis is commonly found in areas without safe water and good sanitation. At-risk groups include… Agricultural and fishing populations Women performing domestic chores Image: http://www.sciencephoto.com/media/299106/enlarge

Schistosomiasis is commonly found in areas without safe water and good sanitation. At-risk groups include… Agricultural and fishing populations Women performing domestic chores Irrigation workers Image: http://cdn.wn.com/pd/1a/27/1c5e17dd1004b9e7d3283e38808f_grande.jpg

Schistosomiasis is commonly found in areas without safe water and good sanitation. At-risk groups include… Agricultural and fishing populations Women performing domestic chores Irrigation workers Refugees “Off track” tourists Image: http://informafrica.com/wp-content/uploads/2011/07/congo-refugees.jpg

…but schistosomiasis is largely a disease of children. Children who swim and play in infested waters School-aged children (10-14 yrs) are the highest at-risk group Causes growth stunts, affects memory and IQ http://www.theaccessproject.com/index.php/about/ntd/ http://twmrf.com/new_page_7.htm http://www.human-healths.com/tag/what-is-schistosomiasis-continued http://www.who.int/wormcontrol/statistics/useful_info/en/index1.html Top image: http://www.who.int/wormcontrol/statistics/useful_info/en/index1.html Middle right: http://www.human-healths.com/tag/what-is-schistosomiasis-continued Bottom left: http://twmrf.com/new_page_7.htm Bottom right: http://www.theaccessproject.com/index.php/about/ntd/ Urinary schistosomiasis affects 66 million children throughout 54 countries.

Schistosomiasis causes great morbidity and mortality in the developing world > 200 million people are infected worldwide, 600 million at risk Image: http://www.path.cam.ac.uk/~schisto/schistosoma/schisto_pathology_HS.html

Schistosomiasis causes great morbidity and mortality in the developing world > 200 million people are infected worldwide, 600 million at risk 85% of infections in sub-Saharan Africa About 280,000 die every year from infection Image: http://www.path.cam.ac.uk/~schisto/schistosoma/schisto_pathology_HS.html

Schistosomiasis causes great morbidity and mortality in the developing world > 200 million people are infected worldwide, 600 million at risk 85% of infections in sub-Saharan Africa About 280,000 die every year from infection Morbidity – growth stunting, cognitive impairment, hepatic fibrosis, urinary obstruction, cancer Image: http://www.path.cam.ac.uk/~schisto/schistosoma/schisto_pathology_HS.html

There are two forms of Schistosomiasis Acute Rash (Swimmer’s itch) Fever Cough Chills Muscle aches Rash: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002298/figure/A001321.B2059/?report=objectonly

There are two forms of Schistosomiasis Acute Chronic Rash (Swimmer’s itch) Fever Cough Chills Muscle aches Abdominal pain Ascites Enlarged liver Splenomegaly Blood in stool Diarrhea Hematuria (blood in urine) Dysuria (painful urination) Varicose veins Seizures Paralysis Varicose veins: http://www.nejm.org/doi/full/10.1056/NEJMicm0803551 Rash: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002298/figure/A001321.B2059/?report=objectonly Seizures and paralysis will only occur if the schistosome eggs reach the brain or spinal cord

Biopsy is the primary method of diagnosing schistosomiasis Use fecal smears and urine tests to visualize schistosome eggs Image: http://www.cartercenter.org/news/features/h/schistosomiasis/parasite-fighting-medicine-nigeria.html presence of eggs is definitive diagnosis Children infected with schistosomiasis show vials of blood-red urine.

Biopsy is the primary method of diagnosing schistosomiasis Use fecal smears and urine tests to visualize schistosome eggs Blood in urine can be detected using chemical reagent strips Image: http://www.cartercenter.org/news/features/h/schistosomiasis/parasite-fighting-medicine-nigeria.html presence of eggs is definitive diagnosis Children infected with schistosomiasis show vials of blood-red urine.

Blood tests also help confirm diagnosis but… Positive results may only indicate past exposure Latency period 6-8 weeks since it takes time for the eggs to develop and stimulate an immune response Image: http://www.sciencephoto.com/media/299102/enlarge

Blood tests also help confirm diagnosis but… Positive results may only indicate past exposure Tests are not positive until the patient has been infected for 6-8 weeks Latency period 6-8 weeks since it takes time for the eggs to develop and stimulate an immune response Image: http://www.sciencephoto.com/media/299102/enlarge

Some other diagnostic methods For tissue biopsy in case no eggs are found in fecal or urine samples: Colonoscopy Endoscopy Liver biopsy Colonoscopy Image: http://www.fivestarslaw.com/wp-content/uploads/2011/10/colonoscopy.gif

Some other diagnostic methods For tissue biopsy in case no eggs are found in fecal or urine samples: Colonoscopy Endoscopy Liver biopsy To measure extent of infection: MRI CT Ultrasound Chest x-rays Echocardiograms Colonoscopy Image: http://www.fivestarslaw.com/wp-content/uploads/2011/10/colonoscopy.gif MRI Image: http://www.magnet.fsu.edu/education/tutorials/magnetacademy/mri/images/mri-scanner.jpg

How was schistosome parasite discovered? Theodor Bilharz 1825-1862 First described by Theodor Bilharz in 1851 Kasr-el-Aini hospital in Cairo Post-mortem examination Image: http://www.path.cam.ac.uk/~schisto/schistosoma/schisto_background.html "After my attention had been drawn to the liver, I soon found a white long helminth in the blood of the portal vein in quantity, which I assumed to be a nematode but which I immediately recognised as something new. The microscope revealed a splendid distomum with a flat body and a curving tail which exceeded the body about ten times in length...”

The Life Cycle of the Schistosome relies on two hosts Snails grow schistosome sporocysts that develop into free-swimming cercariae. Cercariae attach to and penetrate human skin, and migrate through blood vessels to reach portal blood system. During migration, cercariae develop into male and female adult parasitic worms which incorporate human proteins into surface structure causing little or no immune response. Parasite mating occurs in portal blood system and eggs are produced. Eggs stimulate a strong immune response. Some eggs migrate through bowel or bladder and are shed in feces or urine, while other eggs migrate to other tissues. Eggs shed into urine or feces may reach maturity in freshwater and infect susceptible snails.

The Life Cycle of the Schistosome relies on two hosts Intermediate host: snail Definitive host: human Adult stages have two sexes Bottom image: http://www.path.cam.ac.uk/~schisto/schistosoma/Adult_worms.jpg

There are many forms of schistosomes that cause disease in humans S. mansoni – causes intestinal schistosomiasis and is prevalent in 52 countries of Africa, the Caribbean, the Eastern Mediterranean and South America Image: http://pathmicro.med.sc.edu/parasitology/trematodes.htm

There are many forms of schistosomes that cause disease in humans S. mansoni – causes intestinal schistosomiasis and is prevalent in 52 countries of Africa, the Caribbean, the Eastern Mediterranean and South America S. haematobium – causes urinary schistosomiasis and affects 54 countries in Africa and Eastern Mediterranean Image: http://www.path.cam.ac.uk/~schisto/schistosoma/map.haematobium.gif

There are many forms of schistosomes that cause disease in humans S. mansoni – causes intestinal schistosomiasis and is prevalent in 52 countries of Africa, the Caribbean, the Eastern Mediterranean and South America S. haematobium – causes urinary schistosomiasis and affects 54 countries in Africa and Eastern Mediterranean S. japonicum – causes intestinal schistosomiasis in the Pacific region (aka ‘Katayama’ disease)

There are many forms of schistosomes that cause disease in humans S. mansoni – causes intestinal schistosomiasis and is prevalent in 52 countries of Africa, the Caribbean, the Eastern Mediterranean and South America S. haematobium – causes urinary schistosomiasis and affects 54 countries in Africa and Eastern Mediterranean S. japonicum – causes intestinal schistosomiasis in the Pacific region (aka ‘Katayama’ disease) S. mekongi – causes intestinal schistosomiasis in 7 African countries

There are many forms of schistosomes that cause disease in humans S. mansoni – causes intestinal schistosomiasis and is prevalent in 52 countries of Africa, the Caribbean, the Eastern Mediterranean and South America S. haematobium – causes urinary schistosomiasis and affects 54 countries in Africa and Eastern Mediterranean S. japonicum – causes intestinal schistosomiasis in the Pacific region (aka ‘Katayama’ disease) S. mekongi – causes intestinal schistosomiasis in 7 African countries S. intercalatum - found in 10 African countries

Infection induces T-cell response Increase in TNF, IL-1 and IL-6 Granuloma formation Image: http://www.path.cam.ac.uk/~schisto/schistosoma/liver_granuloma.png

How do we treat schistosomiasis? First line drug: Praziquantel Treats all forms of schistosomiasis No side effects Image: http://www.malacsoc.org.uk/the_Malacologist/BULL45/snailbornedisease.htm

How do we treat schistosomiasis? First line drug: Praziquantel Treats all forms of schistosomiasis No side effects Oxamniquine Intestinal schistosomiasis Image: http://www.revolutionhealth.com/images/multum/Mebendazole%20100%20mg-TEV.jpg

How do we treat schistosomiasis? First line drug: Praziquantel Treats all forms of schistosomiasis No side effects Oxamniquine Intestinal schistosomiasis Metrifonate Urinary schistosomiasis Image: http://img8.tokobagus.com/45/71/4553718_7778411.jpg Neguvon = Trichlorfon = Metrifonate This is the metrifonate used to treat cattles, horses, pigs

Praziquantel may target the parasite’s calcium ion channels Mechanism and target is unknown Image: http://www.asia.ru/images/target/photo/51233861/Praziquantel.jpg Prevents newly hatched worms from growing or multiplying Increases exposure of schistosome antigens – elicits immune response

Praziquantel may target the parasite’s calcium ion channels Mechanism and target is unknown Causes severe spasms and paralysis of worms’ muscles caused by influx of Ca2+ ions Image: http://www.asia.ru/images/target/photo/51233861/Praziquantel.jpg Prevents newly hatched worms from growing or multiplying Increases exposure of schistosome antigens – elicits immune response

Praziquantel may target the parasite’s calcium ion channels Mechanism and target is unknown Causes severe spasms and paralysis of worms’ muscles caused by influx of Ca2+ ions Metabolized through cytochrome p450 pathway via CYP3A4 Image: http://www.asia.ru/images/target/photo/51233861/Praziquantel.jpg Prevents newly hatched worms from growing or multiplying Increases exposure of schistosome antigens – elicits immune response

Praziquantel has many limitations Ineffective against juvenile schistosomes Image: http://2.bp.blogspot.com/_kWKqQEHEdf0/TJkOHZiRbOI/AAAAAAABClU/0TLdH1WN3K0/s1600/252525.jpg

Praziquantel has many limitations Ineffective against juvenile schistosomes Develops resistance Resistant strains in Egypt and Senegal Image: http://www.sciencedirect.com/science/article/pii/S016947589901621X Resistance to S. japonicum

Praziquantel has many limitations Ineffective against juvenile schistosomes Develops resistance Resistant strains in Egypt and Senegal High rates of reinfection Image: http://www.sciencedirect.com/science/article/pii/S016947589901621X Resistance to S. japonicum

Praziquantel has many limitations Ineffective against juvenile schistosomes Develops resistance Resistant strains in Egypt and Senegal High rates of reinfection Cannot be taken by HIV/AIDS patients on Rifampin (inhibits CYP3A4) Image: http://www.soi.wide.ad.jp/class/20090060/slides/07/img/26.png

Part of the treatment plan needs to include prevention strategies Health education/hygiene Installation of safe water supply Image: http://medilinkz.org/old/healthtopics/water/WaterAfrica2002.htm

Part of the treatment plan needs to include prevention strategies Health education/hygiene Installation of safe water supply Treatment of water supply with molluscicides Image: http://ecx.images-amazon.com/images/I/51g%2BBttiFwL._SL500_AA300_.jpg

Part of the treatment plan needs to include prevention strategies Health education/hygiene Installation of safe water supply Treatment of water supply with molluscicides Vaccine – not yet developed Image: http://www.tropika.net/report/Chinnock-20091027-Report-Vaccination/images/Chinnock-20091027-Report-Vaccination_f1.png

Works Cited Griffiths, Jeffrey. "MPH/CEE241 Biology of Water and Health, Fall 2007 - Tufts OpenCourseWare." Tufts University, 2008. Web. 2 Mar. 2012. http://ocw.tufts.edu/Content/55/lecturenotes/703050/703095 "Parasites - Schistosomiasis." Centers for Disease Control and Prevention, 02 Nov. 2010. Web. 2 Mar. 2012. http://www.cdc.gov/parasites/schistosomiasis/biology.html Pearce, Edward J., and Andrew S. MacDonald. "The Immunobiology of Schistosomiasis."Nature Reviews 2 (2002): 499-511. 2002. Web. 2 Mar. 2012. "Schistosomiasis." MicrobiologyBytes, 28 Jan. 2007. Web. 2 Mar. 2012. http://www.microbiologybytes.com/introduction/Schisto.html "Schistosomiasis." World Health Organization, Jan. 2012. Web. 2 Mar. 2012. http://www.who.int/mediacentre/factsheets/fs115/en/ Stewart, Terry. "SRG Introduction to Schistosomiasis." University of Cambridge: Department of Pathology, 2010. Web. 2 Mar. 2012. http://www.path.cam.ac.uk/~schisto/schistosoma/index.html