Future directions: The road to elimination

Considerable optimism surrounds Mass Drug Administration (MDA) for the control of schistosomiasis globally, for which praziquantel (PZQ) has served as the cornerstone since its inception in 1979. Numerous studies have claimed that preventive chemotherapy (i.e. 40 mg/kg of praziquantel), given annually or biannually, can significantly reduce the prevalence and intensity of infection and control morbidity in the long term (Molyneux 2004; Molyneux and Hotez 2005; Brady et al. 2006; Engels et al. 2006; Fenwick 2006; Kabatereine et al. 2007; Hotez 2008; Hotez et al. 2009; Bockarie et al. 2013). In the last decade, close to one billion US dollars has been raised for MDA campaigns against neglected tropical diseases (NTDs) largely from international donors (e.g., Merck KgaA, World Bank, Unites States Agency for International Development (USAID), British Department for International Development (DIFD), Geneva Global and the Bill and Melinda Gates Foundation) and delivered vertically to local endemic communities through national health care services largely using unpaid volunteers (Brady et al. 2006; Merck 2013). In total, 28 million children have been treated for schistosomiasis to date through the Merck Praziquantel Donation Program (Merc 2013). Since 2007, Merck has been providing WHO annually (free of charge) with up to 25 million tablets (Hotez et al. 2009). In the medium term, the company will increase that number tenfold to 250 million tablets per year (Rollinson et al. 2013). The donation commitment for the entire continent of Africa amounts to € 17.2 million Euros (Rollinson et al. 2013). 1 Tropical Medicine and Global Health, Griffith University, Logan Campus, University Drive, Meadowbrook QLD. Despite the commitment to MDA programs, it is becoming increasingly clear that the sustainable control of schistosomiasis will require an integrated, inter-sectorial approach that goes beyond deworming (Parker and Tim 2011). While the global use of PZQ is being scaled up, there are also growing concerns about inadequate drug coverage, low cure rates, poor drug compliance, lack of baseline information prior to the commencement of MDA programs, their inadequate monitoring and evaluation once commenced and the potential for the development of drug resistance (Parker and Tim 2011). PZQ is effective against all the human schistosome species and is currently the drug of choice to treat infection (Liu et al. 2011; Olliaro et al. 2011). However, parasitological cure depends on the treatment dose. A recent systematic review and meta-analysis of 52 clinical trials showed that, compared with placebo, a dosage of 30-60 mg/kg PZQ produced a cure rate of around 76% (range from 67-83%) for human schistosomiasis (Liu et al. 2011). No significant differences in cure rates were found among subjects infected with S. haematobium, S. japonicum or S. mansoni. The cure rate of the drug at a 40 mg/kg dosage (which is the current dose recommended by the WHO) was 52% (range from 49-55%) compared with 91% (range from 88%-92%) when dosages were increased to 60, 80, 100 mg/kg, divided into two or more doses (Liu et al. 2011. In the early 1980s and again in 2011, WHO, in an attempt to optimize PZQ use for the treatment of schistosomiasis, launched a series of multi-country trials, comparing the efficacy and safety of 40 mg/kg and 60 mg/kg in schistosome-infected patients in Asia, Africa and the Americas (Olliaro et al. 2011). In these clinical trials the 40 mg/kg dose was found to be effective (92% cure rate) and better tolerated than the higher 60 mg/kg dose (Olliaro et al. 2011). However, given the small sample size in each country (approximately 200 per site) the generalizability of these findings are questionable.