Abstract

Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies. Given the heavy reliance on PZQ for mass drug administration, there has been considerable research on the potential of parasites developing resistance to the drug, resulting in decreased drug efficacy. However, there have been comparatively fewer studies of other factors that can potentially alter PZQ efficacy. Here, we investigate whether host PZQ metabolism contributes towards variable cure rates. We evaluate factors that can influence the metabolism of PZQ and the resultant effect on the efficacy of PZQ treatment to determine factors that potentially influence an individual’s response to the drug. The literature search was directed at published studies from three online databases: Web of Science, PubMed, and EMBASE. The search terms for the review comprised of ([praziquantel OR PZQ] AND [schistosom* OR bilharzia] AND [pharmaco*]) and included studies evaluating PZQ metabolism. Publications were categorised into pharmacokinetics, drug–drug interactions, pharmacogenetics, and metabolite analysis. Forty publications describing human and experimental studies fitted the inclusion criteria and were subjected to data extraction and analysis. The analyses showed that variable exposure to PZQ was associated with alterations in the liver’s capacity to metabolise PZQ and observed drug–drug interactions. Other factors influencing the efficacy of PZQ were brand, formulation, and co-administered food. Although some work has been performed on metabolite identification, there was minimal information on PZQ’s metabolic pathway, and no pharmacogenetics studies were identified. The study indicated that in both human and experimental studies alterations in the liver’s capacity to metabolise PZQ as well as drug–drug interactions affected systemic levels of PZQ that could result in variable cure rates. The study confirmed previous findings of higher antischistosomal activity of (R)-PZQ enantiomer when administered alone compared to the racemate at the same dose as well as improved efficacy when the drug is administered with food. The study also highlighted the need for more comprehensive studies of the PZQ metabolic pathway and PZQ pharmacogenetic studies in humans.

Highlights

  • Schistosomiasis is a prominent public health problem [1], with the majority of affected people residing in Africa [2]

  • Schistosomiasis is a neglected tropical disease caused by parasitic worms, and its control is heavily reliant on the drug praziquantel (PZQ)

  • Reports of individuals not being cured of schistosomiasis after a treatment have raised concerns about drug efficacy and the potential for the development of drug resistance

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Summary

Introduction

Schistosomiasis is a prominent public health problem [1], with the majority of affected people residing in Africa [2]. Praziquantel (PZQ) is the drug of choice to treat schistosomiasis and is widely used in preventive chemotherapy (PCT) programs (as defined by WHO) [3] across Africa to treat intestinal and urogenital schistosomiasis infections caused by Schistosoma mansoni and S. haematobium parasites, respectively [4]. Mass drug administration (MDA) of PZQ in PCT to treat schistosome infection and reduce associated morbidity has been a success, with an estimated 235 million people treated with PZQ in 2018 alone [5]. Studies suggest that its action arises from the (R)-PZQ enantiomer disrupting the schistosome calcium ion homeostasis causing uncontrolled muscle contraction and death in adult worms [9, 10]. PZQ targets only adult schistosomes; the drug is not effective against the larval stages infections [11]

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