Current global estimates are that at least 750 million people are at risk of food-borne trematodiasis (>10% of the world’s population) with more than 40 million people infected. Over 100 species of food-borne trematodes are known to parasitize humans, many of which also infect domestic animals. However, food-borne trematodiasis is a truly neglected tropical disease.

Humans become infected when eating raw or undercooked aquatic products (e.g. fish, crustacean and water plants) that contain metacercariae. Half a dozen of food-borne trematodes pose a significant public-health and economic problem. These include the liver flukes (Clonorchis sinensis, Fasciola hepatica, F. gigantica, Opisthorchis felineus and O. viverrini) and the lung flukes (Paragonimus spp.). Whilst the majority of infections are asymptomatic and usually characterized by a small parasite load, patients with high infection intensities are at risk of morbidity. The public-health impact of food-borne trematodiasis is considerable and is primarily driven by morbid sequelae due to inflammatory lesions and damage of tissues and target organs. The most serious complication in clonorchiasis and opisthorchiasis patients is cholangiocarcinoma. The annual mortality rate due to food-borne trematodiasis is difficult to quantify, but has been estimated at 10,000. New research is needed to estimate the global burden of food-borne trematodiasis, and this should embrace a societal perspective (e.g. burden in livestock to be included).

There are only two drugs currently recommended for the treatment and control of food-borne trematodiasis, praziquantel and triclabendazole. Discovery and development research on novel trematocidal drugs has been neglected over the past decades. There is one notable exception, namely the recent advances made at STI with peroxidic compounds, (i) artemisinin and its semi-synthetic derivatives (e.g. artemether and artesunate); (ii) a synthetic peroxide, the 1,2,4-trioxolane OZ78; and (iii) the Chinese anthelminthic tribendimidine. We found that the artemisinins, OZ78 and tribendimidine have a broad spectrum of trematocidal activity in rodent models. These promising findings prompted us to launch studies in a larger animal model, hence studies testing the efficacy of artemether and OZ78 in F. hepatica-infected sheep are ongoing with our partners at the University of Naples in Italy and from Novartis Animal Health here in Basel. It is also important to note that, since artemether is a highly efficacious and safe antimalarial drug that has been administered to millions of patients the world over, phase II clinical testing on fascioliasis has been initiated with Prof. Sanaa Botros from the Theodor Bilharz Institute in Cairo, Egypt. Finally, two PhD students will embark on this project shortly with an emphasis on mechanism of action and preclinical studies.

 

Prof. Dr. Jennifer Keiser

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Further reading

Keiser & Utzinger (2007). Advances in the discovery and development of trematocidal drugs. Expert Opinion in Drug Discovery 2 (suppl. 1), S9-23.

Keiser & Utzinger (2007). Food-borne trematodiasis: current chemotherapy and advances with artemisinins and synthetic trioxolanes. Trends in Parasitoloy 23 (in press)

photo left: Sheep liver containing F. hepatica
photo right: Scanning electron microscopy of a F. hepatica trematode treated with OZ78. Blebbing and roughening visible on the dorsal anterior part of the tegument.

 

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