How improvements to drug effectiveness impact mass drug administration for control and elimination of schistosomiasis

Schistosomiasis affects more than 230 million people worldwide. Control and elimination of this parasitic infection is based on mass drug administration of praziquantel (PZQ), which has been in use for several decades. Because of the limitations of the efficacy of PZQ especially against juvenile worms, and the threat of the emergence of resistance, there is a need to consider alternative formulations or delivery methods, or new drugs that could be more efficacious. We use an individual-based stochastic model of parasite transmission to investigate the effects of possible improvements to drug efficacy. We consider an increase in efficacy compared to PZQ, as well as additional efficacy against the juvenile life stage of schistosome parasites in the human host, and a slow-release formulation that would provide long-lasting efficacy for a period of time following treatment.

Analyses suggest a drug with a high efficacy of 99%, or with efficacy lasting 24 weeks after treatment, are the two most effective individual improvements to the drug profile of PZQ. A drug with long lasting efficacy is most beneficial when MDA coverage is low. However, when prevalence of infection has already been reduced to a low level, a high efficacy is the most important factor to accelerate interruption of transmission. Our results indicate that increased efficacy against juvenile worms can only result in modest benefits, but the development of a new drug formulation with higher efficacy against adult worms or long-lasting efficacy would create an improvement to the community impact over the currently used formulation.

Author summary

The World Health Organization has set the target of elimination of schistosomiasis as a public health problem by 2030. Currently, praziquantel is the sole drug used in mass drug administration (MDA) for schistosomiasis, raising concerns about the potential evolution of resistance and whether an improved drug profile would be necessary to achieve elimination and the more ambitious goal of interruption of transmission. We present the results from an individual-based stochastic mathematical model that simulates schistosome transmission and the impact of MDA. Three potential improvements to the properties of the drug are considered: improved efficacy, long lasting efficacy post a single treatment and improved efficacy against the juvenile life stage of the schistosome. Our findings reveal that with good coverage, an improved drug efficacy is best at reducing prevalence and achieving interruption of transmission. However, when MDA quality is compromised due to low coverage, infrequent treatment or high rates of non-adherence, then a long-lasting efficacy performs best. There is only a modest benefit of improved drug efficacy against juvenile schistosomes. These results highlight the importance of good MDA program and inform future drug development aims.