Antischistosomal Natural Compounds: Present Challenges for New Drug Screens

Schistosomiasis, or bilharzias, is a neglected disease that remains a considerable public health problem in tropical and subtropical regions. This parasitic disease is the most important human helminth infection in terms of morbidity and mortality and is a growing concern worldwide. It is estimated that more than 200 million people have been infected and that 779 million are at risk of infection, resulting in 280,000 deaths annually (van der Werf et al., 2003; Steinmann et al., 2006). Schistosomiasis is caused by blood-dwelling fluke worms of the genus Schistosoma and is endemic in African, Asian and South American countries. The main disease-causing species are S. mansoni, S. haematobium, and S. japonicum. S. mansoni is the most widely distributed, affecting people in Africa, the Middle East, South America, and the Caribbean, while S. japonicum is confined to China, Indonesia, and the Philippines. S. haematobium is found in Africa and the Middle East. The adult worms colonise the veins of either the portal system (S. mansoni and S. japonicum) or the urinary bladder plexus (S. haematobium) and can live for years or even decades in human hosts; thus, the disease runs a chronic and debilitating course. Egg production is responsible for both the transmission of the parasite and the aetiology of the disease. Schistosomal species are distinguished by differences in their morphology, both in their parasite stages and in their eggs; further species distinction is made by the species of intermediate host snails that support transmission of the parasite (Gryseels et al., 2006). The global strategy for the control of schistosomiasis is by chemotherapy. Systematic searching for chemotherapeutic drugs began almost a century ago, and the development of praziquantel (PZQ) in 1970 was essential for a reduction in morbidity and mortality due to schistosomiasis. Currently, treatment is still based on the use of PZQ, but the long-term application of PZQ results in decreased efficiency and serious concerns regarding the onset of resistance. In addition, PZQ has no prophylactic properties and is ineffective against larval stages of parasites (schistosomula), meaning that for effective treatment and sustainable control, PZQ must be given on a regular basis. Thus, it is prudent to search for novel therapeutics, and recent discussions have focused on reawakening the need to search for alternatives to PZQ (Caffrey, 2007; Doenhoff et al., 2008; Fenwick et al., 2003; Hagan et al., 2004; Keiser & Utzinger, 2007).