Clinical Efficacy and Tolerability of Praziquantel for Intestinal and Urinary Schistosomiasis—A Meta-analysis of Comparative and Non-comparative Clinical Trials
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{"title"=>"Clinical efficacy and tolerability of praziquantel for intestinal and urinary schistosomiasis-a meta-analysis of comparative and non-comparative clinical trials", "type"=>"journal", "authors"=>[{"first_name"=>"Julien", "last_name"=>"Zwang", "scopus_author_id"=>"12809052800"}, {"first_name"=>"Piero L.", "last_name"=>"Olliaro", "scopus_author_id"=>"7005144054"}], "year"=>2014, "source"=>"PLoS neglected tropical diseases", "identifiers"=>{"issn"=>"19352735", "scopus"=>"2-s2.0-84973427306", "pui"=>"610718078", "doi"=>"10.1371/journal.pntd.0003286", "isbn"=>"1935-2735", "sgr"=>"84973427306", "pmid"=>"25412105"}, "id"=>"ad4cc5c9-41ef-3da3-b44a-320267028dd7", "abstract"=>"BACKGROUND: Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma 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%), S. mansoni (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 S. japonicum, 77.1% (68.4-85.1) for S. haematobium, 76.7% (95%CI 71.9-81.2) for S. mansoni, and 63.5% (95%CI 48.2-77.0) for mixed S. haematobium/S. mansoni infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. mansoni and 30 mg/kg for S. haematobium. The mean ERR was 95% for S. japonicum, 94.1% for S. haematobium, and 86.3% for S. mansoni. 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.\\n\\nCONCLUSIONS/SIGNIFICANCE: 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.", "link"=>"http://www.mendeley.com/research/clinical-efficacy-tolerability-praziquantel-intestinal-urinary-schistosomiasisa-metaanalysis-compara", "reader_count"=>53, "reader_count_by_academic_status"=>{"Unspecified"=>6, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Other"=>5, "Student > Master"=>10, "Student > Bachelor"=>2, "Lecturer"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>6, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Other"=>5, "Student > Master"=>10, "Student > Bachelor"=>2, "Lecturer"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>10, "Engineering"=>1, "Environmental Science"=>2, "Nursing and Health Professions"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>19, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>3, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>19}, "Chemistry"=>{"Chemistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>10}, "Environmental Science"=>{"Environmental Science"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "group_count"=>11}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1802027", "https://ndownloader.figshare.com/files/1802028", "https://ndownloader.figshare.com/files/1802029", "https://ndownloader.figshare.com/files/1802030", "https://ndownloader.figshare.com/files/1802031", "https://ndownloader.figshare.com/files/1802032"], "description"=>"<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>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247756, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0003286.s001", "https://dx.doi.org/10.1371/journal.pntd.0003286.s002", "https://dx.doi.org/10.1371/journal.pntd.0003286.s003", "https://dx.doi.org/10.1371/journal.pntd.0003286.s004", "https://dx.doi.org/10.1371/journal.pntd.0003286.s005", "https://dx.doi.org/10.1371/journal.pntd.0003286.s006"], "stats"=>{"downloads"=>15, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_Efficacy_and_Tolerability_of_Praziquantel_for_Intestinal_and_Urinary_Schistosomiasis_8212_A_Meta_analysis_of_Comparative_and_Non_comparative_Clinical_Trials_/1247756", "title"=>"Clinical Efficacy and Tolerability of Praziquantel for Intestinal and Urinary Schistosomiasis—A Meta-analysis of Comparative and Non-comparative Clinical Trials", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802024"], "description"=>"<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>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247753, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.t001", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Main_characteristics_of_the_studies_included_S_haematobium_sh_S_japonicum_sj_and_mixed_infections_S_haematobium_S_intercalatum_si_/1247753", "title"=>"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).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802022"], "description"=>"<p>as, artesunate; ox, oxamniquine; pzq, praziquantel; sp, sulfadoxine-pyrimethamine; mq, mefloquine; comp, comparator; ci, confidence interval; unit next to the drug: dose in mg/kg; RR, risk ratio; I<sup>2</sup> (Higgins' I squared) is calculated for pooled subgroups as  =  100%×(<i>Q</i> - df)/<i>Q</i>, where <i>Q</i> is Cochran's heterogeneity statistic and df the degrees of freedom.</p>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247751, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.g005", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_of_risk_ratio_of_cure_rates_with_95_CIs_S_mansoni_PZQ_40_mg_kg_vs_other_regimens_/1247751", "title"=>"Forest plot of risk ratio of cure rates with 95%CIs, S. mansoni, PZQ 40 mg/kg vs. other regimens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802023"], "description"=>"<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>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247752, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.g006", "stats"=>{"downloads"=>8, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PZQ_egg_reduction_rates_with_95_CIs_by_species_and_dose_/1247752", "title"=>"PZQ egg reduction rates with 95% CIs by species and dose.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802021"], "description"=>"<p>comp, comparator; ci, confidence interval; pzq, praziquantel; unit next to the drug: dose in mg/kg; RR, risk ratio; I<sup>2</sup> (Higgins' I squared) is calculated for pooled subgroups as  =  100%×(<i>Q</i> - df)/<i>Q</i>, where <i>Q</i> is Cochran's heterogeneity statistic and df the degrees of freedom.</p>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247750, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.g004", "stats"=>{"downloads"=>7, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_of_risk_ratios_of_cure_rates_with_95_CIs_S_mansoni_PZQ_40_mg_kg_vs_other_PZQ_regimens_/1247750", "title"=>"Forest plot of risk ratios of cure rates with 95%CIs, <i>S. mansoni</i>, PZQ 40 mg/kg vs. other PZQ regimens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802018"], "description"=>"<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>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247747, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_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_/1247747", "title"=>"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).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802026"], "description"=>"<p>Legend. ci, confidence interval.</p><p>Adverse event incidence, praziquantel 40 mg/kg.</p>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247755, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.t003", "stats"=>{"downloads"=>2, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adverse_event_incidence_praziquantel_40_mg_kg_/1247755", "title"=>"Adverse event incidence, praziquantel 40 mg/kg.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802025"], "description"=>"<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>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247754, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.t002", "stats"=>{"downloads"=>9, "page_views"=>76, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_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_/1247754", "title"=>"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.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802020"], "description"=>"<p>as, artesunate; ol, oltipraz; pzq, praziquantel; sp, sulfadoxine-pyrimethamine; met, metrifonate, mq, mefloquine; p, placebo; comp, comparator; unit next to the drug: dose in mg/kg; RR, risk ratio; I<sup>2</sup> (Higgins' I squared) is calculated for pooled subgroups as  =  100%*(<i>Q</i> - df)/<i>Q</i>, where <i>Q</i> is Cochran's heterogeneity statistic and df the degrees of freedom.</p>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247749, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.g003", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_of_relative_risks_of_cure_rates_with_95_CIs_S_haematobium_PZQ_40_mg_kg_vs_comparators_/1247749", "title"=>"Forest plot of relative risks of cure rates with 95%CIs, <i>S. haematobium</i>, PZQ 40 mg/kg vs. comparators.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-20 02:51:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1802019"], "description"=>"<p>sh, <i>S. haematobium</i>; si, <i>S. intercalatum</i>; sj, <i>S. japonicum</i>; sm, <i>S. mansoni</i>.</p>", "links"=>[], "tags"=>["praziquantel dose", "Schistosoma species", "generalizable conclusions", "subject", "egg reduction rate", "ci", "Clinical Efficacy", "sites efficacy", "cr", "age Effects", "mg", "haematobium", "err", "mansoni", "ae", "273 studies", "control treatment", "cure rate"], "article_id"=>1247748, "categories"=>["Biological Sciences"], "users"=>["Julien Zwang", "Piero L. Olliaro"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0003286.g002", "stats"=>{"downloads"=>9, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_of_praziquantel_PZQ_cure_rates_with_95_CIs_by_species_and_dose_all_age_groups_/1247748", "title"=>"Forest plot of praziquantel (PZQ) cure rates with 95% CIs by species and dose (all age groups).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-20 02:51:03"}

PMC Usage Stats | Further Information

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