Fascioliasis Rebecca Flint

Fascioliasis has world wide effects WHO designated extremely neglected disease Cases in 51 different countries 17 million people affected WHO has designated fascioliasis as one of the extremely neglected diseases. Cases have been seen in 51 different countries in the past 25 years. The highest known rates of human infection are in the Andean highlands of Bolivia and Peru. It is the second most common trematode infection in the Middle East and North Africa. It mainly affects children in poor rural areas. The estimated number of infected people is at least 2.4 million and might be as high as 17 million.

Oral-fecal transmission route Reservoir in livestock Watercress The fasciola is a liver fluke that is passed through the oral-fecal route. It most commonly occurs where cattle or sheep vectors contaminate water and people become infected by drinking water carrying the worm or eating raw vegetables, specifically watercress, that are exposed to the contaminated water and not cooked prior to eating.

1. Unfertilized eggs are released in stool usually from cattle or sheep and fertilized in water. 2. Miracidia hatch and invade the snail intermediate host where they continue to develop Parasite goes through 3 developmental stages in the snail, the sporocysts then rediae and last the free- swimming cercariae are released from the snail the metacercariae encyst on water plants 5. Humans become sick by eating metacercariae that have attached to plants 6. The metacercariea move into the duodenum and migrate to the biliary ducts where they mature and eventually are excreted in the stool

Disease manifests in the liver Chronic phase Producing eggs in bile ducts Asymptomatic Symptomatic Acute phase Flukes traveling to bile ducts Nausea, vomiting, abdominal pain Inflammation and bleeding Liver tissue destruction The acute phase of the disease occurs when the flukes are traveling through the small intestinal wall into the liver and the bile duct. It usually begins 4 to 7 days after ingestion of the fasciola and may last from weeks to months. This phase is often asymptomatic, but patients who do experience symptoms may experience gastrointestinal bleeding, inflammation, abdominal pain, nausea, vomiting and diarrhea. Patients may also experience destruction of the liver tissue. The chronic disease occurs when the flukes have made it to the bile ducts and begin producing eggs. symptomatic disease causes Severe, lasting damage while many patients in the chronic phase remain asymptomatic

Diagnosis can be difficult Stool ova test ELISA or Western Blot Liver ultrasound

Few drugs have been used for treatment Bithionol - Less effective Triclabendazole - 1983 - Effective against early stage parasites - Inhibits parasitic microtubule formation - Resistance in 1995 Bithionol causes morphological changes

Cathepsin L proteases vaccine testing Fascilitate in tissue penetration, feeding, and immune system evasion Cathepsin L1 and L2 are the major fasciola proteases Secreted from the epithelial cells lining the gut of fasciola. Only tested in sheep and cattle

FhSAP2 as a potential vaccine Potential to protect against subsequent fasciola hepatica metacercariae infections Fluke burden Reduced 83.3% with cDNA-FhSAP2 Reduced 60% with FhSAP2 protein FhSAP2 is a Fasciola antigen. All vaccinated animals had less liver damage

Kapplan-Meier analysis to estimate the survival probability over the time after challenge in mice vaccinated with FhSAP2 or cDNA-FhSAP2 compared to positive controls. PC includes mice vaccinated with PBS in FA and vaccinated with the empty pFLAG-CMV−2 plasmid. Log-rank test determined that there are statistical differences (P<.05) between survival probability of DNA-FhSAP2-vaccinated group compared to the PC group

Difficulty controlling Fasciola spread Individualized control plans Separation of livestock and farming Sanitation Cooked vegetables

References http://www.stanford.edu/class/humbio103/ParaSites2006/Fascioliasis/index.htm http://perutravelnews.info/Peru_geography.html http://www.dpd.cdc.gov/dpdx/html/fascioliasis.htm http://www.bvgh.org/Biopharmaceutical-Solutions/Global-Health-Primer/Diseases/cid/ViewDetails/ItemID/23.aspx Farid Z, Kamal M, Woody J (1988). Treatment of acute toxemic fascioliasis. Trans R Soc Trop Med Hyg, 82, 299. Dawes B. Some apparent effects of Bithionol (Actamer) on Fasciola hepatica. Nature. 209. 424–425. http://www.cdc.gov/parasites/fasciola.html http://www.sciencedirect.com/science/article/pii/S0020751903001711 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260556/ http://www.who.int/foodsafety/foodborne_disease/Fascioliasis.pdf http://www.who.int/bulletin/archives/77(4)340.pdf Neglected tropical diseases of the Middle East and North Africa: Review of their prevalence, distribution and opportunities for control http://ac.els-cdn.com/S001448000700010X/1-s2.0-S001448000700010X-main.pdf?_tid=82eb0beb26d3784c63b3fcd658db039e&acdnat=1333563684_9e8fd6d27e3ffb1fd0161e28213982e4 http://ac.els-cdn.com/S0020751903001711/1-s2.0-S0020751903001711-main.pdf?_tid=34f4d59141feb9d940a11d5c27187d3b&acdnat=1333563744_ba4fe537c7008eb34a64f709d662597b http://ac.els-cdn.com/S0304401709001642/1-s2.0-S0304401709001642-main.pdf?_tid=2428d0ca1d59c164e22da2549d1bead9&acdnat=1333563799_59532b3db68dd198cec5000e8417e16d http://ac.els-cdn.com/S1090023399903775/1-s2.0-S1090023399903775-main.pdf?_tid=241c67a32596ceb3ca75909744fc71c6&acdnat=1333563903_2ff3d34d9679ff21d2ec7451b180156a