Praziquantel: Getting the dosage right
For 25 years praziquantel has been the recommended treatment for schistosomiasis, a parasite transmitted by freshwater snails in Africa, Asia and Latin America, and infecting some 200 million people worldwide.
Long experience with the WHO-recommended single dosage of 40 mg/kg has shown it to be safe and relatively efficacious. However, a higher 60 mg/kg single dose has also been used in some endemic countries as have been split doses on certain occasions. This has aimed to improve efficacy, reduce side-effects and reduce rates of reinfection – although systematic evidence on this remains scarce.
To fill in the knowledge gaps, TDR in 2003 launched a series of multi-country clinical trials to optimize the use of praziquantel for the treatment of schistosomiasis. The trials compared the efficacy and safety of the most common single dosages of praziquantel (40 and 60 mg/kg) in patients with the different parasite species in Asia, Africa and the Americas. Results of those trials are now reshaping treatment policies around the world.
- In the Philippines where the parasite Schistosoma japonicum is predominant, the 40 mg/kg dose has now been demonstrated to be as effective and better tolerated than the higher dose 60 mg/kg dose. Results published in JPID (1) have been taken up by national policy-makers, who affirmed their commitment to the lower dosage.
- In Brazil where another species, S. mansoni , is predominant, the reinfection rate post-treatment was lower in the 60 mg/kg group than among those who received the 40 mg/kg dose. Results presented at a recent meeting in Brazil thus support the use of the higher dose in that country (2).
- In the United Republic of Tanzania and Mauritania, where S. mansoni predominates, trials of the two comparative dosages have been concluded, although results are still being analysed.
- All studies will contribute to a meta-analysis of preferred praziquantel dosage by species and region.
Such findings underline the fact that different drug treatments may be required for different environments in light of variations in species, infection rates, social interactions, etc. At the same time, high overall rates of schistosomiasis reinfection (between 30-50% depending on the species and the region) suggest the need to address more directly behavioural and environmental factors in endemic communities, along with the continued search for improved diagnostics, drugs and vaccines.
Contact: Dr Piero Olliaro
References:
1. Belizario VY et al. Efficacy and safety of 40 mg/kg and 60 mg/kg doses of praziquantel in the treatment of schistosomiasis. Journal of Pediatric Infectious Diseases, 2008, 3:27–34.
2. Galvão AF et al. Impact of treatment with praziquantel on Schistosoma mansoni infection in adolescents from an endemic area of north-east Brazil. In: 11° Simpósio internacional sobre esquistossomose [Proceedings of the 11th international symposium on schistosomiasis], 20–22 August 2008, Salvador, Brazil. p. 80.