Efficacy of praziquantel has been maintained over four decades (from 1977 to 2018): A systematic review and meta-analysis of factors influence its efficacy

Author summary Schistosomiasis is a water-borne disease caused by a group of flatworm parasites known as schistosomes. The drug praziquantel has been used since the 1970s to treat schistosomiasis with some variable measures of efficacy reported. Reasons for the variation can be related to host attributes or parasite attributes. We conducted this study to determine factors affecting drug efficacy and if the efficacy has altered in the past four decades. We identified 146 scientific articles that reported efficacy levels of praziquantel treatment for schistosomiasis as determined by cure rate (CR) and/or egg reduction rate (ERR). We conclude that praziquantel treatment is still effective for schistosomiasis even after four decades of usage. Praziquantel efficacy levels increased with drug dose. Our study showed the majority of studies reported high ERR (>80%) even among studies that reported low CR (<50%). Even in the studies reporting low CR, ERR were high indicating that treatment did reduce infection intensity even though it did not completely remove the infection in some people. Since schistosome morbidity is related to infection intensity, our results support the use of ERR as an indicator that helps avoid underestimation of praziquantel treatment efficacy and health impact. Background The antihelminthic drug praziquantel has been used as the drug of choice for treating schistosome infection for more than 40 years. Although some epidemiological studies have reported low praziquantel efficacy in cure rate (CR) and/or egg reduction rate (ERR), there is no consistent robust evidence of the development of schistosome resistance to praziquantel (PZQ). There is need to determine factors that lead to variable treatment CR and/or ERR. Therefore, we conducted a systematic review and meta-analysis to review CR and ERR as well as identify their predictors. Methodology/Principal findings In this systematic review and meta-analysis, a literature review was conducted using Biosis Citation Index, Data Citation Index, MEDLINE, and Web of Science Core Collection all of which were provided through Web of Science. Alongside these, EMBASE, and CAB abstracts were searched to identify relevant articles. Random effect meta-regression models were used to identify the factors that influence CR and/or ERR by considering differences in host characteristics and drug dose. In total, 12,127 potential articles were screened and 146 eligible articles (published from 1979 to 2020) were identified and included for the meta-analysis. We found that there has been no significant reduction in CR or ERR over the study period. The results showed more variability in CR, compared with ERR which was more consistent and remained high. The results showed a positive effect of PZQ treatment dose with the current recommended dose of 40 mg/kg body weight achieving 57% to 88% CR depending on schistosome species, age of participants, and number of parasitological samples used for diagnosis, and ERR of 95%. Conclusions/Significance Based on a review of over 40 years of research there is no evidence to support concerns about schistosomes developing resistance to PZQ. These results indicate that PZQ remains effective in treating schistosomiasis.

Automated summary

The study found that praziquantel treatment for schistosomiasis remains effective even after four decades of usage, with efficacy levels increasing with drug dose. Majority of studies reported high egg reduction rates, even among those with low cure rates. The results support the use of egg reduction rate as an indicator for treatment efficacy and health impact.