Clinical Efficacy and Tolerability of Praziquantel for Intestinal and Urinary Schistosomiasis—A Meta-analysis of Comparative and Non-comparative Clinical Trials

<div><p>Background</p><p>Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different <i>Schistosoma</i> species.</p><p>Methodology/Principal Findings</p><p>A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any <i>Schistosoma</i> species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo). Most studied were in school-aged children (64%), <i>S. mansoni</i> (58%), and the 40 mg/kg dose (56%); 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n = 17,017) and egg reduction rate (ERR, n = 13,007); safety as adverse events (AE) incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2–98.0) for <i>S. japonicum</i>, 77.1% (68.4–85.1) for <i>S. haematobium</i>, 76.7% (95%CI 71.9–81.2) for <i>S. mansoni, and</i> 63.5% (95%CI 48.2–77.0) for mixed <i>S. haematobium/S. mansoni</i> infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. <i>mansoni</i> and 30 mg/kg for <i>S. haematobium.</i> The mean ERR was 95% for <i>S. japonicum</i>, 94.1% <i>for S. haematobium</i>, and 86.3% for <i>S. mansoni</i>. No significant relationship between dose and ERR was detected. Tolerability was assessed in 40 studies (12,435 subjects). On average, 56.9% (95%CI 47.4–67.9) of the subjects receiving praziquantel 40 mg/kg experienced an AE. The incidence of AEs ranged from 2.3% for urticaria to 31.1% for abdominal pain.</p><p>Conclusions/Significance</p><p>The large number of subjects allows generalizable conclusions despite the inherent limitations of aggregated-data meta-analyses. The choice of praziquantel dose of 40 mg/kg is justified as a reasonable compromise for all species and ages, although in a proportion of sites efficacy may be lower than expected and age effects could not be fully explored.</p></div

Flow chart of the number of studies and patients screened and eligible for the efficacy analyses of cure rate (CR) and egg reduction rates (ERR).

<p>Of the 41 comparative studies identified, 19 directly compared different doses and schedules of PZQ; 7 compared praziquantel with artesunate combined with praziquantel, sulfalene, sulfamethoxypyrazine/pyrimethamine, or mefloquine; 6 with artesunate alone; 3 with metrifonate; 1 with nitrifonate and 1 with metrifonate+nitrifonate; 6 with oxamniquine, 4 with oltipraz, 1 with albendazole, 1 with mefloquine, and 3 with PZQ in combination with artemether, albendazole, or metrifonate.</p

Adverse event incidence, praziquantel 40 mg/kg.

<p>Legend. ci, confidence interval.</p><p>Adverse event incidence, praziquantel 40 mg/kg.</p

PZQ egg reduction rates with 95% CIs by species and dose.

<p>ci, confidence interval; sh, <i>S. haematobium</i>; si, <i>S. intercalatum</i>; sj, <i>S. japonicum</i>; sm, <i>S. mansoni</i>.</p

Main characteristics of the studies included – <i>S. haematobium</i> (sh), <i>S. japonicum</i> (sj) and mixed infections <i>S. haematobium-S. intercalatum</i> (si).

<p>Main characteristics of the studies included – <i>S. haematobium</i> (sh), <i>S. japonicum</i> (sj) and mixed infections <i>S. haematobium-S. intercalatum</i> (si).</p

Cure rates (CR) and egg reduction rates (ERR) with 95% confidence intervals (95%CI) calculated by boot-strapping by age-group, species and praziquantel dose.

<p>Legend: sh, <i>S. haematobium</i>; si, <i>S. intercalatum</i>; sj, <i>S. japonicum</i>; sm, <i>S. mansoni</i>.</p><p>Cure rates (CR) and egg reduction rates (ERR) with 95% confidence intervals (95%CI) calculated by boot-strapping by age-group, species and praziquantel dose.</p

Number of people invited to provide feedback and number of responses received.

<p>Of the 53 total responses received, 47 were comprehensive, and 6 were void.</p

TPP for a point-of-care test for the detection of <i>Taenia solium</i> taeniasis in humans.

<p>TPP for a point-of-care test for the detection of <i>Taenia solium</i> taeniasis in humans.</p

Characteristics of <i>Taenia solium</i> cysticerci in the brain with respect to cyst viability and diagnostic parameters.

<p>Characteristics of <i>Taenia solium</i> cysticerci in the brain with respect to cyst viability and diagnostic parameters.</p

TPP for a point-of-care test for the diagnosis of human neurocysticercosis.

<p>TPP for a point-of-care test for the diagnosis of human neurocysticercosis.</p