* By Michael R. Reich, Agnes Brinkmann, and Ramesh Govindaraj.

The most important development in recent decades in the treatment of schistosomiasis is the discovery of praziquantel. This pharmaceutical product is the first anthelminthic drug to fulfill the World Health Organization’s requirements for population-based chemotherapy of a broad range of parasitic infections (Wegner, 1981). This chapter presents some of the therapeutic precursors of praziquantel, and then describes the discovery and initial testing of praziquantel, with particular attention to the role of WHO. Competing drugs for schistosomiasis treatment and the veterinary uses of praziquantel are briefly discussed.

This report does not provide a review of the biology and epidemiology of schistosomiasis, or of the clinical and pharmacological properties of praziquantel, since a vast literature on these topics exists (for a review of schistosomiasis morbidity, see Gryseels, 1989; for a review of praziquantel therapy, see Kumar and Gryseels, 1994). Schistosomiasis is estimated to infect 200 million people in the world today, with an exposed population of about 600 million people, and occurs mainly in rural populations in frequent contact with freshwater. The disease is endemic in 74 tropical countries, and involves five species of schistosome worms: Schistosoma mansoni, S. haematobium, S. japonicum, S. intercalatum, and S. mekongi. Praziquantel is effective treatment for all five species and for both major types of morbidity (urinary lesions for S. haematobium, and hepatic lesions for the other species). The spread of schistosomiasis is often associated with water resource development projects (dams and irrigation schemes) that create new habitats for the snail vectors through ecosystem changes and alter human behaviour and settlement patterns in ways that increase exposure to the parasite (Hunter et al., 1993).

Praziquantel was the result of collaborative work between two German pharmaceutical manufacturers: Bayer A.G., Leverkusen, and E. Merck, Darmstadt. The anthelminthic activity of pyrazinoisoquinoline derivatives was discovered in 1972 in the laboratories of Bayer, and was followed up by J. Seubert and others at E. Merck (Andrews, 1981; Seubert et al., 1977a). Praziquantel’s curative efficacy against a broad spectrum of platyhelminths pathogenic to man was confirmed in testing during the following years (Wegner, 1984). The compound was patented in Germany in December 1973, and in the United States of America in 1977 (Seubert et al., 1977b). Praziquantel became available in Europe after 1978 (King and Mahmoud, 1989), and generally available on the international market in the 1980s. Table 2.1 presents data on Bayer/E. Merck’s registration of praziquantel patents, along with the estimated patent expiry dates.

Table 2.1: Bayer/E. Merck’s praziquantel patents

Source: Bayer AG.

Praziquantel also has significant veterinary uses, and was approved in 1980 for such uses in the United States of America (Scrip, 1981), followed by approval and registration for human use in 1982 by the Food and Drug Administration (Scrip, 1981).