2Schistosomiasis, AKA Bilharzia Parasitic disease caused by several species of flatwormAffects many in developing countries (it’s estimated that 207M have the disease and that of those, 120M are symptomatic)Can contract it by wading or swimming in lakes, ponds and other bodies of water infested with the parasite’s snail host.
4A Brief History... First described by German pathologist Theodore Maximilian BilharzBilharz performed autopsies on Egyptianpatients who had died from the disease:found male & female parasite eggs in the liverportal system, bladder.Later seen in Japan, called Katayama feverSymptoms: rash on legs, fever, diarrhoea, bloody stools emaciation, edema death.
5Classification Phylum: Platyhelminthes (flatworms) Subclass: Digenea (alt. gen. seen in life cycle)Order: StrigeidaFamily: Schistosomatidae (blood flukes)Subfamily: SchistosomatinaeGenus: SchistosomaSpecies: S. mansoni S. japonicum S. haematobium S. indicum
7Life Cycle (Eggs larvae into snail) Parasite eggs released into freshwater (from human urine, feces)Eggs hatch ciliated miracidia, free swimmingMiracidia find & infect snail host (different species prefer diff’t snail sp.)Each miracidia transforms into many fork-tailed, free swimming forms called cercariae within 4-6 weeks of entering snail.Cercariae leave snail and move into water at a rate of 1500/day for up to 18 days.Miracidia larva with cilia
8Life Cycle (Into human lymphatics lungs liver) 6. Cercariae find a human host,penetrate skin, and differentiate intolarval forms called schistosomulae.7. Migrate through the host’s skin,gain access to the lymphatic system.8. Travel to the lungs (stay 3-8 days and ~70% are eliminated)9. Migrate to liver portal system, mature into male & female adultsCircariae need to find a human host within a day, or they die.Circariae find a human host and lose their tail as they’re penetrating the skin.Cercariae with forked tail
9Life Cycle (maturation movement to target organs egg production) 10. In liver, m & f pair up female inserts herself into the gynecophoral canal of male they are now ‘paired’. 11. Migrate to favoured sites: S. mansoni – mesenteric venules of large bowel & rectum S. japonicum – mesenteric veins of the small intestine S. haematobium – perivesical venous plexus surrounding the bladderPaired male & female
10Life Cycle (Egg release) 12. Females release eggs. Egg characteristics - Covered in microbarbs cling to vascular endothelium - Pores, which allow the release of 1) Antigens 2) Enzymes (aid in passage of eggs through host tissues) 12. Eggs enter lumen of excretory organs 50% passed out of body 50% trapped in tissues, carried away by blood circulation, lymph.Japonicum can release up to 2000 eggs/day!!
11Acute Infection (Early) Cercariae penetrate skin rash - called schistosome or swimmer’s itch.Eggs laid in target organs release antigens cause Katayama fever - fever - urticaria - malaise- diarrheaUticaria: itchy, raised, swollen bumps
12Chronic Infection (Late) Symptoms of chronic infection caused by eggs that travel to various parts of bodyEggs remain trapped in host tissues secrete Ags granulomatous inflammatory immune responseGranulomas: macrophages surrounded by lymphocytes (CD4, CD8 Tcells), which aggregate at site of infection.Fibroblast cells also at site of infection.During late stage of chronic infection, they replace the granulomas. Their prolif. is stim. by factors produced by the schistosome egg, & by cytokines from macrophages & CD4 Tcells.Fibroblasts mediate collagen deposition in the granuloma, leading to fibrosis (=fibrous connective tissues developmentUticaria: itchy, raised, swollen bumps
14Chronic Infection (When eggs meet the GI tract) In S. mansoni infectionsWall of colon is damaged as eggs pass throughInflamm. response ulcers, inflammatory polypsCan lead to fibrosisClinically: diarrhea, abdominal painEggs can also accumulate in the appendixCan lead to appendicitis (inflammation of the appendix)
15Chronic Infection (When eggs meet the meet the liver/spleen) Hepatosplenic schistosomiasisEggs carried by portal circulation liverGranulomatous responseGranulomas are walled off with fibrous tissue fibrosis obstructs portal veins portal hypertensionEsophageal varices (dilated esophageal veins, which drain the liver bursting can cause bleeding to death. Caused directly by portal hypertension.)Splenomegaly (enlarged spleen, due to fibrosis)gradient greater than 10 mmHg is considered portal hypertension. At gradients greater than 10 mmHg, blood flow though the hepatic portal system is redirected from the liver into areas with lower venous pressures eg. The esophageal vein, which usually drains blood from the esophagus.
16Chronic Infection (When eggs meet the meet the heart) In those with severe hepatosplenic schistosomiasisBlood gets shunted directly back to the heart (doesn’t pass through liver).Eggs accumulate in heart, sometimes lodged in pulmonary arterioles.Form granulomas block pulmonary circulation pulmonary hypertension.Can lead to right ventricular strain, and eventually cardiovascular collapse.
17Chronic Infection (When eggs meet the meet the genitourinary areas & CNS) Genitourinary complicationsEggs lodge themselves in wall of bladder & can develop into polypsPolyps can erode, ulcerate & cause hematuria (blood cells in urine)Eggs lodge in ureters and urethra, cause lumps and lesions kidney failureEggs lodge into ovaries, the uterus, cervix, fallopian tubes lumps complications incl. infertility(For the men: eggs can also lodge into the testes and the prostate )CNS complicationsS. haematobium and S. mansoni can migrate to the spineS. japonicum found in the brain and causes encephalopathy (general brain dysfunction)
18Diagnosis Microscopic Detection Take stool or urine sample to detect eggsS. haematobium eggs are oval and have a spike at the tipS. japonicum eggs small and almost spherical with tiny spineS. mansoni eggs have a spike on the side (spine)S. mansoniS. japonicumS. haematobium
19Diagnosis Antibody tests An earlier and more sensitive form of detectionSome complicationsCross-reactivity with other helminthic infections (other flatworm parasites)Can’t tell the difference between current and old infections as antibodies stay long after infection is over.Can’t tell you anything about overall worm burden so we can’t tell how serious the infection is
20Diagnosis Antigen tests: Detect antigens in blood with immunoelectrophoresis2 types are detected though share similar complications with antibody testsMolecular detection:20-25% of schistosomiasis genome has been sequenced can use 2 probes to detect S. mansoni DNA in human bloodGenome sequencing has the potential to yield DNA vaccines
21PreventionFor travelers it’s easy- don’t swim in fresh, stagnant water (running water is better, still not safe).Harder in endemic areas people are dependent on nearby freshwater.Focused on education, eliminating snail nesting groundsMolluscicides can be used to eliminate snails.Proper irrigation systems and engineering are keyThere are ways to build irrigation and canalization systems that don’t allow snails to inhabit the surrounding areaHowever, many irrigation/canalization projects since the 50s have ignored UN instructions, may have contributed to spread of the parasite
22TreatmentSwimmer’s itch and Katayama Fever are usually treated symptomatically.Chemotherapy is treatment of choice - Praziquantel is most widely used drug.PraziquantelExtremely well tolerated, few side effectsBroad-spectrum antihelminthic drug (antihelminthic= drugs that expel parasitic worms)Cures schistosomiasis in 80–90% of patients, 90% reduction in egg excretion in those not curedCauses worm muscles contract – cannot hold onto human tissuesResistance has been reported in Egypt and Senegal
23Treatment Others: Metrifonate against S. haematobium Niridazole against S. japonicumOxamniquine against S. mansoniWHO recently approved use of combo of 3 drugs at once (rule is always no more than 2) to cure a few related diseases (incl. Schistosomiasis) in hopes that eradication will be faster.ComplicationsDrugs ineffective when fibrosis has developed - treatment is then focused on managing the complications (e.g. portal hypertension)Anticonvulsants may be needed in patients with CNS complications (S. japonicum).
24VaccinationHumoural environment hostile to parasites, but eggs stay in blood for weeks without significant attackIrradiated cercariae vaccine very effective in clinical trials. Delivery complications & difficulty in establishing proper safety standards make it problematic as human vaccine.Currently testing combination-protein and combination DNA vaccines but so far unsuccessful. Some issues:Co-evolution: disease has existed since 4000 BC – has developed ways to evade human immune responses.Antigen sharing - we share a number of antigens with the parasite; difficult to create vaccine that doesn’t cross-react with our own cells.Evidence suggests that our immune response actually helps mature female lay eggs
25Discussion Why isn’t there a vaccine yet? What factors make vaccine development difficult?Should we focus on vaccine development and if so, who should shoulder the cost?Some have argued that wide-scale treatment of schistosomiasis should not be a priority- what factors can affect this decision?Since the 1950’s, specifications and design criteria have been made available by the United Nations (UN) which show how dams, irrigation schemes, and similar projects an be constructed so that they are not suitable habitats for the snails and also make it more difficult for the local population to come into contact with the water. Unfortunately, many projects have been completed without taking these specifications and design criteria into account.Q: Should we put more emphasis on this?