Schistosomiasis Neena Davisson March 15, 2012 Schistosomiasis is a parasitic infection • Schistosomiasis is caused by a trematode helminth Schistosomiasis is an ancient disease Schistosome eggs have been recovered from both Chinese and Egyptian mummies Schistosomiasis is an ancient disease Hieroglyphics also refer to the disease. Schistosomiasis is prevalent in tropical and sub-tropical areas Schistosomiasis is commonly found in areas without safe water and good sanitation. At-risk groups include… • Agricultural and fishing populations Schistosomiasis is commonly found in areas without safe water and good sanitation. At-risk groups include… • Agricultural and fishing populations • Women performing domestic chores 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 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 …but schistosomiasis is largely a disease of children. 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 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 Schistosomiasis causes great morbidity and mortality in the developing world • > 200 million people are infected worldwide, 600 million at risk • 85% of infections in subSaharan Africa • About 280,000 die every year from infection • Morbidity – growth stunting, cognitive impairment, hepatic fibrosis, urinary obstruction, cancer There are two forms of Schistosomiasis Acute • Rash (Swimmer’s itch) • Fever • Cough • Chills • Muscle aches There are two forms of Schistosomiasis Chronic Acute • 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 Biopsy is the primary method of diagnosing schistosomiasis • Use fecal smears and urine tests to visualize schistosome eggs 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 Children infected with schistosomiasis show vials of blood-red urine. Blood tests also help confirm diagnosis but… • Positive results may only indicate past exposure 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 Some other diagnostic methods • For tissue biopsy in case no eggs are found in fecal or urine samples: • Colonoscopy • Endoscopy • Liver biopsy 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 How was schistosome parasite discovered? Theodor Bilharz 1825-1862 "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 The Life Cycle of the Schistosome relies on two hosts • Intermediate host: snail • Definitive host: human • Adult stages have two sexes 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 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 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 How do we treat schistosomiasis? • First line drug: Praziquantel • Treats all forms of schistosomiasis • No side effects How do we treat schistosomiasis? • First line drug: Praziquantel • Treats all forms of schistosomiasis • No side effects • Oxamniquine • Intestinal schistosomiasis How do we treat schistosomiasis? • First line drug: Praziquantel • Treats all forms of schistosomiasis • No side effects • Oxamniquine • Intestinal schistosomiasis • Metrifonate • Urinary schistosomiasis Praziquantel may target the parasite’s calcium ion channels • Mechanism and target is unknown 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 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 Praziquantel has many limitations • Ineffective against juvenile schistosomes Praziquantel has many limitations • Ineffective against juvenile schistosomes • Develops resistance • Resistant strains in Egypt and Senegal Resistance to S. japonicum Praziquantel has many limitations • Ineffective against juvenile schistosomes • Develops resistance • Resistant strains in Egypt and Senegal • High rates of reinfection 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) Part of the treatment plan needs to include prevention strategies • Health education/hygiene • Installation of safe water supply Part of the treatment plan needs to include prevention strategies • Health education/hygiene • Installation of safe water supply • Treatment of water supply with molluscicides 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 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