Efficacy of Two versus Three-Day Regimens of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Military Personnel in Northern Cambodia: An Open-Label Randomized Trial
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{"title"=>"Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for uncomplicated malaria in military personnel in Northern Cambodia: An open-label randomized trial", "type"=>"journal", "authors"=>[{"first_name"=>"Chanthap", "last_name"=>"Lon", "scopus_author_id"=>"36704891200"}, {"first_name"=>"Jessica E.", "last_name"=>"Manning", "scopus_author_id"=>"55917203300"}, {"first_name"=>"Pattaraporn", "last_name"=>"Vanachayangkul", "scopus_author_id"=>"26023960900"}, {"first_name"=>"Mary", "last_name"=>"So", "scopus_author_id"=>"56147086500"}, {"first_name"=>"Darapiseth", "last_name"=>"Sea", "scopus_author_id"=>"55250459800"}, {"first_name"=>"Youry", "last_name"=>"Se", "scopus_author_id"=>"25926030000"}, {"first_name"=>"Panita", "last_name"=>"Gosi", "scopus_author_id"=>"14119855700"}, {"first_name"=>"Charlotte", "last_name"=>"Lanteri", "scopus_author_id"=>"7004704455"}, {"first_name"=>"Suwanna", "last_name"=>"Chaorattanakawee", "scopus_author_id"=>"55250823400"}, {"first_name"=>"Sabaithip", "last_name"=>"Sriwichai", "scopus_author_id"=>"15835566400"}, {"first_name"=>"Soklyda", "last_name"=>"Chann", "scopus_author_id"=>"55250764000"}, {"first_name"=>"Worachet", "last_name"=>"Kuntawunginn", "scopus_author_id"=>"39061415000"}, {"first_name"=>"Nillawan", "last_name"=>"Buathong", "scopus_author_id"=>"8232553000"}, {"first_name"=>"Samon", "last_name"=>"Nou", "scopus_author_id"=>"55774777800"}, {"first_name"=>"Douglas S.", "last_name"=>"Walsh", "scopus_author_id"=>"7402052368"}, {"first_name"=>"Stuart D.", "last_name"=>"Tyner", "scopus_author_id"=>"55249604400"}, {"first_name"=>"Jonathan J.", "last_name"=>"Juliano", "scopus_author_id"=>"16444870200"}, {"first_name"=>"Jessica", "last_name"=>"Lin", "scopus_author_id"=>"35763356600"}, {"first_name"=>"Michele", "last_name"=>"Spring", "scopus_author_id"=>"36882063300"}, {"first_name"=>"Delia", "last_name"=>"Bethell", "scopus_author_id"=>"56456096600"}, {"first_name"=>"Jaranit", "last_name"=>"Kaewkungwal", "scopus_author_id"=>"6701733827"}, {"first_name"=>"Douglas", "last_name"=>"Tang", "scopus_author_id"=>"36746996100"}, {"first_name"=>"Char Meng", "last_name"=>"Chuor", "scopus_author_id"=>"53879450600"}, {"first_name"=>"Prom", "last_name"=>"Satharath", "scopus_author_id"=>"56146748100"}, {"first_name"=>"David", "last_name"=>"Saunders", "scopus_author_id"=>"35228043400"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84899754743", "doi"=>"10.1371/journal.pone.0093138", "pui"=>"373008410", "pmid"=>"24667662", "scopus"=>"2-s2.0-84899754743", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"51ce8bbd-0639-3ada-91c3-6adc43621f1e", "abstract"=>"INTRODUCTION: Emerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.\\n\\nMETHODS: Efficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were compared as a nested open-label evaluation within a malaria cohort study in 222 otherwise healthy volunteers (18% malaria-infected at baseline). The first 80 volunteers with slide-confirmed Plasmodium falciparum or vivax malaria were randomized 1:1 to receive either regimen (total dose 360 mg dihydroartemisinin and 2880 mg piperaquine) and followed weekly for up to 6 months. The primary endpoint was malaria recurrence by day 42. Volunteers with vivax infection received primaquine at study discharge with six months follow-up.\\n\\nRESULTS: Eighty patients (60 vivax, 15 falciparum, and 5 mixed) were randomized to dihydroartemisinin-piperaquine. Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen (95% CI 69-94) and 90% for the three-day regimen (95% CI 75-97). PCR-adjusted falciparum efficacy was 75% in both groups with nearly half (45%) still parasitemic at Day 3. Plasma piperaquine levels were comparable to prior published reports, but on the day of recrudescence were below measurable in vitro piperaquine IC50 levels in all falciparum treatment failures.\\n\\nCONCLUSIONS: In the brief period since introduction of dihydroartemisinin-piperaquine, there is early evidence suggesting declining efficacy relative to previous reports. Parasite IC50 levels in excess of plasma piperaquine levels seen only in treatment failures raises concern for clinically significant piperaquine resistance in Cambodia. These findings warrant improved monitoring of clinical outcomes and follow-up, given few available alternative drugs.\\n\\nTRIAL REGISTRATION: ClinicalTrials.gov NCT01280162.", "link"=>"http://www.mendeley.com/research/efficacy-two-versus-threeday-regimens-dihydroartemisininpiperaquine-uncomplicated-malaria-military-p", "reader_count"=>46, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>7, "Other"=>6, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>7, "Other"=>6, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>2, "Nursing and Health Professions"=>3, "Biochemistry, Genetics and Molecular Biology"=>7, "Mathematics"=>1, "Medicine and Dentistry"=>23, "Agricultural and Biological Sciences"=>5, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>23}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Brazil"=>1, "United Kingdom"=>2, "Spain"=>1}, "group_count"=>6}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1435274"], "description"=>"<p>*Randomization goal met, 2 withdrew. **Prolonged QTc. <sup>¥</sup>PCR-corrected speciation. <sup>a</sup>Not included are 2<sup>nd</sup> recurrences (1 Pf, 1 Pv, 1 mixed). <sup>b</sup>Not included are 2nd recurrences (2 Pf, 5 Pv) and a 3<sup>rd</sup> recurrence (1 Pv). <sup>#</sup>Study discharge varied, median 115 days follow-up.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "schematic", "inset"], "article_id"=>974337, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_Schematic_Inset_and_Trial_Profile_/974337", "title"=>"Study Schematic Inset and Trial Profile.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435275"], "description"=>"<p>(A) Concentration–time profiles (geometric mean concentrations with 95% CI) for ACPR and recrudescent groups. There were no statistically significant differences beween groups at any timepoint. (B) AUC<sub>0-∞</sub> (2 compartment analysis) in ACPR and LTF groups. Black lines represent geomean with 95%CI. Note that AUC could not be calculated in 4 and 2 patients in the ACPR and LTF groups, respectively due to limited timepoints (only 3) in the terminal phase.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "plasma", "piperaquine", "acpr", "recrudescent"], "article_id"=>974338, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_plasma_piperaquine_levels_between_ACPR_and_recrudescent_patients_/974338", "title"=>"Comparison of plasma piperaquine levels between ACPR and recrudescent patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435279"], "description"=>"<p>(A) No statistical difference between regimens for all-species recurrence at primary endpoint Day 42 (p = 0.63) and at day of discharge (p = 0.84). (B) In persons with an initial <i>falciparum</i> parasitemia (alone or mixed), there was no difference in true <i>falciparum</i> recrudescence at Day 42 (p = 0.73) and at day of study discharge (p = 0.91). (C) In persons with an initial <i>vivax</i> parasitemia (alone or mixed), there was no difference in <i>vivax</i> recurrence at Day 42 (0.94) and at day of study discharge (p = 0.22).</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "incidence", "recurrence", "modified", "intention-to-treat", "42"], "article_id"=>974342, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cumulative_incidence_of_recurrence_by_modified_intention_to_treat_analysis_at_Day_42_and_study_discharge_/974342", "title"=>"Cumulative incidence of recurrence by modified intention-to-treat analysis at Day 42 and study discharge.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435282"], "description"=>"<p>The pink line represents the plasma piperaquine concentration, and the green line represents Day 0 IC<sub>50</sub>, with time of recurrence noted by arrows. Plasma piperaquine is shown as piperaquine phosphate salt concentration (MW 999·56) to match IC<sub>50</sub> calculation method. NI = new infection in case 091. The IC<sub>50</sub> for 149RC could not be assessed due to non-recovery of parasites from the clinical sample.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "plasma", "concentration-time", "profiles", "cases"], "article_id"=>974345, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Piperaquine_plasma_concentration_time_profiles_in_relation_to_IC_50_for_cases_of_P_falciparum_recrudescence_/974345", "title"=>"Piperaquine plasma concentration-time profiles in relation to IC<sub>50</sub> for cases of <i>P. falciparum</i> recrudescence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435284"], "description"=>"<p>Error bars indicate +1 standard deviation.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "trough", "qtcf", "intervals", "patients", "treated", "dha-piperaquine", "mg", "divided", "days"], "article_id"=>974347, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mean_trough_QTcF_intervals_for_patients_treated_daily_with_DHA_piperaquine_360_2880_mg_cumulative_divided_over_2_or_3_days_n_8202_8202_40_in_each_group_/974347", "title"=>"Mean trough QTcF intervals for patients treated daily with DHA-piperaquine (360/2880 mg cumulative) divided over 2 or 3 days (n = 40 in each group).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435288"], "description"=>"<p>Cumulative incidence (Kaplan-Meier) of reported <i>vivax</i> recurrence in 2-day (n = 37) versus 3-day (n = 29) regimens following primaquine (PQ) administration at study discharge by monthly follow-up in 66 volunteers over 6 months (P = 0.62). Six cohort volunteers who were not randomized to dihydroartemisinin-piperaquine treatment also developed vivax infection and received primaquine, but are not included in analysis above. *G6PD-normal volunteers received daily primaquine30mg for 14 days whereas G6PD-deficient volunteers received a weekly regimen of 45mg for 8 weeks.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "cumulative", "incidence", "vivax", "recurrence", "primaquine"], "article_id"=>974351, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Six_month_cumulative_incidence_of_reported_vivax_recurrence_following_primaquine_administration_/974351", "title"=>"Six-month cumulative incidence of reported vivax recurrence following primaquine administration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435289"], "description"=>"<p>All data are number (%) unless otherwise indicated. There were no statistical or clinically significant differences between groups. *Non-PCR adjusted. **Only 1 sample in this subgroup so actual parasitemia reported.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "enrolled", "patients"], "article_id"=>974352, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Baseline_characteristics_of_enrolled_patients_according_to_treatment_arm_/974352", "title"=>"Baseline characteristics of enrolled patients according to treatment arm.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435290"], "description"=>"<p>All data are number [%(95% CI)] unless otherwise indicated; CIs are based on binomial (exact) calculations; p-values are for Fisher’s exact test. *Wilcoxon test was used for comparing parasite and fever clearance times. <sup>¥</sup><i>Vivax</i> recurrence in those with initial <i>vivax</i> infection. <b><sup>€</sup></b><i>Falciparum</i> recurrences in volunteers with initial <i>falciparum</i> or mixed infections (n = 2 in each arm) were all true recrudescences by PCR. One subject with initial <i>falciparum</i> infection developed <i>vivax</i> infection at Day 42 and was counted as failure in the all-species analysis only. *PP analysis excludes subjects withdrawn or lost-to-follow-up. **ITT analysis treats subjects withdrawn or lost-to-follow-up as treatment failures. ***Mean (median) follow-up duration 102 days (115 days).</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "responses", "pcr-corrected", "outcomes"], "article_id"=>974353, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Therapeutic_responses_and_PCR_corrected_outcomes_by_treatment_regimen_/974353", "title"=>"Therapeutic responses and PCR-corrected outcomes by treatment regimen.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435291"], "description"=>"<p>*Mann-Whitney U test comparing 2 and 3 day treatment groups. **PK analysis could not be performed in 10 and 7 subjects from Group 1 and 2, respectively due to insufficient time points. PK Parameters are expressed as medians and <i>(25–75% percentiles)</i>, with significantly different values in <b>bold</b>.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "calculated", "2-compartment", "comparing", "three-day", "courses"], "article_id"=>974354, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pharmacokinetic_parameters_calculated_from_a_2_compartment_model_comparing_two_versus_three_day_courses_of_DHA_piperaquine_/974354", "title"=>"Pharmacokinetic parameters calculated from a 2-compartment model comparing two versus three-day courses of DHA-piperaquine.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435292"], "description"=>"<p>Mean changes from baseline in QTcB and QTcF following daily treatment with DHA-piperaquine (360/2880 mg cumulative dose) divided over 2 versus 3 days.</p>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "qtcf"], "article_id"=>974355, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_QTcB_and_QTcF_interval_changes_according_to_treatment_arm_/974355", "title"=>"QTcB and QTcF interval changes according to treatment arm.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 04:22:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435298", "https://ndownloader.figshare.com/files/1435299", "https://ndownloader.figshare.com/files/1435300", "https://ndownloader.figshare.com/files/1435301", "https://ndownloader.figshare.com/files/1435302", "https://ndownloader.figshare.com/files/1435303", "https://ndownloader.figshare.com/files/1435304"], "description"=>"<div><p>Introduction</p><p>Emerging antimalarial drug resistance in mobile populations remains a significant public health concern. We compared two regimens of dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian border to evaluate national treatment policy.</p><p>Methods</p><p>Efficacy and safety of two and three-day regimens of dihydroartemisinin-piperaquine were compared as a nested open-label evaluation within a malaria cohort study in 222 otherwise healthy volunteers (18% malaria-infected at baseline). The first 80 volunteers with slide-confirmed <i>Plasmodium falciparum</i> or <i>vivax</i> malaria were randomized 1:1 to receive either regimen (total dose 360mg dihydroartemisinin and 2880mg piperaquine) and followed weekly for up to 6 months. The primary endpoint was malaria recurrence by day 42. Volunteers with <i>vivax</i> infection received primaquine at study discharge with six months follow-up.</p><p>Results</p><p>Eighty patients (60 <i>vivax</i>, 15 <i>falciparum</i>, and 5 mixed) were randomized to dihydroartemisinin-piperaquine. Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen (95% CI 69–94) and 90% for the three-day regimen (95% CI 75–97). PCR-adjusted <i>falciparum</i> efficacy was 75% in both groups with nearly half (45%) still parasitemic at Day 3. Plasma piperaquine levels were comparable to prior published reports, but on the day of recrudescence were below measurable <i>in vitro</i> piperaquine IC<sub>50</sub> levels in all <i>falciparum</i> treatment failures.</p><p>Conclusions</p><p>In the brief period since introduction of dihydroartemisinin-piperaquine, there is early evidence suggesting declining efficacy relative to previous reports. Parasite IC<sub>50</sub> levels in excess of plasma piperaquine levels seen only in treatment failures raises concern for clinically significant piperaquine resistance in Cambodia. These findings warrant improved monitoring of clinical outcomes and follow-up, given few available alternative drugs.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href=\"http://clinicaltrials.gov/ct2/show/NCT01280162\" target=\"_blank\">NCT01280162</a></p></div>", "links"=>[], "tags"=>["organisms", "protozoans", "Parasitic protozoans", "Malarial parasites", "Plasmodium falciparum", "Plasmodium malariae", "Plasmodium vivax", "cardiology", "Cardiovascular pharmacology", "Clinical medicine", "clinical trials", "Infectious diseases", "Parasitic diseases", "malaria", "pharmacology", "Clinical pharmacology", "Pharmacodynamics", "Tropical diseases", "research design", "Clinical research design", "three-day", "regimens", "dihydroartemisinin-piperaquine", "uncomplicated", "open-label", "randomized"], "article_id"=>974361, "categories"=>["Biological Sciences"], "users"=>["Chanthap Lon", "Jessica E. Manning", "Pattaraporn Vanachayangkul", "Mary So", "Darapiseth Sea", "Youry Se", "Panita Gosi", "Charlotte Lanteri", "Suwanna Chaorattanakawee", "Sabaithip Sriwichai", "Soklyda Chann", "Worachet Kuntawunginn", "Nillawan Buathong", "Samon Nou", "Douglas S. Walsh", "Stuart D. Tyner", "Jonathan J. Juliano", "Jessica Lin", "Michele Spring", "Delia Bethell", "Jaranit Kaewkungwal", "Douglas Tang", "Char Meng Chuor", "Prom Satharath", "David Saunders"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0093138.s001", "https://dx.doi.org/10.1371/journal.pone.0093138.s002", "https://dx.doi.org/10.1371/journal.pone.0093138.s003", "https://dx.doi.org/10.1371/journal.pone.0093138.s004", "https://dx.doi.org/10.1371/journal.pone.0093138.s005", "https://dx.doi.org/10.1371/journal.pone.0093138.s006", "https://dx.doi.org/10.1371/journal.pone.0093138.s007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Efficacy_of_Two_versus_Three_Day_Regimens_of_Dihydroartemisinin_Piperaquine_for_Uncomplicated_Malaria_in_Military_Personnel_in_Northern_Cambodia_An_Open_Label_Randomized_Trial_/974361", "title"=>"Efficacy of Two versus Three-Day Regimens of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Military Personnel in Northern Cambodia: An Open-Label Randomized Trial", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-03-25 04:22:17"}

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