Dihydroartemisinin-piperaquine versus artesunate-amodiaquine

Superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria

A HASUGIAN, H PURBA, Enny Kenangalem, R Wuwung, E Ebsworth, R Maristela, P PENTTINEN, F Laihad, Nicholas Anstey, Emiliana Tijitra, Ric Price

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background. Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies. Methods. We conducted a randomized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine (DHP) with artesunate-amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42. Results. Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45% (95% confidence interval [CI], 36%-53%) for AAQ and 13% (95% CI, 7.2%-19%) for DHP (hazard ratio [HR], 4.3; 95% CI, 2.5-7.2; P < .001). Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95% CI, 1.2-9.4] and 4.3 [95% CI, 2.2-8.2], respectively; P < .001). By the end of the study, AAQ recipients were 2.95-fold (95% CI, 1.2- to 4.9-fold) more likely to be anemic and 14.5-fold (95% CI, 3.4- to 61-fold) more likely to have carried P. vivax gametocytes. Conclusions. DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia. � 2007 by the Infectious Diseases Society of America. All rights reserved.
    Original languageEnglish
    Pages (from-to)1067-1074
    Number of pages8
    JournalClinical Infectious Diseases
    Volume44
    Issue number8
    Publication statusPublished - 2007

    Fingerprint

    dihydroartemisinin
    Vivax Malaria
    Plasmodium vivax
    Plasmodium falciparum
    Confidence Intervals
    Malaria
    Recurrence
    Plasmodium
    Indonesia
    Antimalarials
    Therapeutic Uses
    piperaquine
    artesunate drug combination amodiaquine
    Drug Resistance
    Anemia

    Cite this

    HASUGIAN, A ; PURBA, H ; Kenangalem, Enny ; Wuwung, R ; Ebsworth, E ; Maristela, R ; PENTTINEN, P ; Laihad, F ; Anstey, Nicholas ; Tijitra, Emiliana ; Price, Ric. / Dihydroartemisinin-piperaquine versus artesunate-amodiaquine : Superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. In: Clinical Infectious Diseases. 2007 ; Vol. 44, No. 8. pp. 1067-1074.
    @article{820e6844f4f44f698e7c9ac2927f6076,
    title = "Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: Superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria",
    abstract = "Background. Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies. Methods. We conducted a randomized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine (DHP) with artesunate-amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42. Results. Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45{\%} (95{\%} confidence interval [CI], 36{\%}-53{\%}) for AAQ and 13{\%} (95{\%} CI, 7.2{\%}-19{\%}) for DHP (hazard ratio [HR], 4.3; 95{\%} CI, 2.5-7.2; P < .001). Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95{\%} CI, 1.2-9.4] and 4.3 [95{\%} CI, 2.2-8.2], respectively; P < .001). By the end of the study, AAQ recipients were 2.95-fold (95{\%} CI, 1.2- to 4.9-fold) more likely to be anemic and 14.5-fold (95{\%} CI, 3.4- to 61-fold) more likely to have carried P. vivax gametocytes. Conclusions. DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia. � 2007 by the Infectious Diseases Society of America. All rights reserved.",
    keywords = "amodiaquine, antiemetic agent, artekin, artesunate, dihydroartemisinin, dihydroartemisinin plus piperaquine, doxycycline, piperaquine, quinine, unclassified drug, antimalarial agent, artemisinin derivative, dihydroquinghaosu, quinoline derivative, sesquiterpene, adolescent, anemia, anorexia, article, ataxia, child, clinical trial, controlled clinical trial, controlled study, drug efficacy, drug safety, drug tolerability, female, follow up, gametocyte, human, infection risk, major clinical study, malaria, male, multidrug resistance, nausea, open study, Plasmodium falciparum, Plasmodium vivax, priority journal, prophylaxis, prospective study, randomized controlled trial, recurrence risk, recurrent infection, tablet, treatment outcome, treatment response, tremor, vomiting, animal, drug effect, drug tolerance, Indonesia, malaria falciparum, physiology, Amodiaquine, Animals, Antimalarials, Artemisinins, Drug Resistance, Multiple, Drug Tolerance, Humans, Malaria, Falciparum, Malaria, Vivax, Quinolines, Sesquiterpenes, Treatment Outcome",
    author = "A HASUGIAN and H PURBA and Enny Kenangalem and R Wuwung and E Ebsworth and R Maristela and P PENTTINEN and F Laihad and Nicholas Anstey and Emiliana Tijitra and Ric Price",
    year = "2007",
    language = "English",
    volume = "44",
    pages = "1067--1074",
    journal = "Clinical Infectious Diseases",
    issn = "1058-4838",
    publisher = "Oxford University Press",
    number = "8",

    }

    Dihydroartemisinin-piperaquine versus artesunate-amodiaquine : Superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. / HASUGIAN, A; PURBA, H; Kenangalem, Enny; Wuwung, R; Ebsworth, E; Maristela, R; PENTTINEN, P; Laihad, F; Anstey, Nicholas; Tijitra, Emiliana; Price, Ric.

    In: Clinical Infectious Diseases, Vol. 44, No. 8, 2007, p. 1067-1074.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Dihydroartemisinin-piperaquine versus artesunate-amodiaquine

    T2 - Superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria

    AU - HASUGIAN, A

    AU - PURBA, H

    AU - Kenangalem, Enny

    AU - Wuwung, R

    AU - Ebsworth, E

    AU - Maristela, R

    AU - PENTTINEN, P

    AU - Laihad, F

    AU - Anstey, Nicholas

    AU - Tijitra, Emiliana

    AU - Price, Ric

    PY - 2007

    Y1 - 2007

    N2 - Background. Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies. Methods. We conducted a randomized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine (DHP) with artesunate-amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42. Results. Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45% (95% confidence interval [CI], 36%-53%) for AAQ and 13% (95% CI, 7.2%-19%) for DHP (hazard ratio [HR], 4.3; 95% CI, 2.5-7.2; P < .001). Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95% CI, 1.2-9.4] and 4.3 [95% CI, 2.2-8.2], respectively; P < .001). By the end of the study, AAQ recipients were 2.95-fold (95% CI, 1.2- to 4.9-fold) more likely to be anemic and 14.5-fold (95% CI, 3.4- to 61-fold) more likely to have carried P. vivax gametocytes. Conclusions. DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia. � 2007 by the Infectious Diseases Society of America. All rights reserved.

    AB - Background. Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies. Methods. We conducted a randomized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine (DHP) with artesunate-amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42. Results. Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45% (95% confidence interval [CI], 36%-53%) for AAQ and 13% (95% CI, 7.2%-19%) for DHP (hazard ratio [HR], 4.3; 95% CI, 2.5-7.2; P < .001). Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95% CI, 1.2-9.4] and 4.3 [95% CI, 2.2-8.2], respectively; P < .001). By the end of the study, AAQ recipients were 2.95-fold (95% CI, 1.2- to 4.9-fold) more likely to be anemic and 14.5-fold (95% CI, 3.4- to 61-fold) more likely to have carried P. vivax gametocytes. Conclusions. DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia. � 2007 by the Infectious Diseases Society of America. All rights reserved.

    KW - amodiaquine

    KW - antiemetic agent

    KW - artekin

    KW - artesunate

    KW - dihydroartemisinin

    KW - dihydroartemisinin plus piperaquine

    KW - doxycycline

    KW - piperaquine

    KW - quinine

    KW - unclassified drug

    KW - antimalarial agent

    KW - artemisinin derivative

    KW - dihydroquinghaosu

    KW - quinoline derivative

    KW - sesquiterpene

    KW - adolescent

    KW - anemia

    KW - anorexia

    KW - article

    KW - ataxia

    KW - child

    KW - clinical trial

    KW - controlled clinical trial

    KW - controlled study

    KW - drug efficacy

    KW - drug safety

    KW - drug tolerability

    KW - female

    KW - follow up

    KW - gametocyte

    KW - human

    KW - infection risk

    KW - major clinical study

    KW - malaria

    KW - male

    KW - multidrug resistance

    KW - nausea

    KW - open study

    KW - Plasmodium falciparum

    KW - Plasmodium vivax

    KW - priority journal

    KW - prophylaxis

    KW - prospective study

    KW - randomized controlled trial

    KW - recurrence risk

    KW - recurrent infection

    KW - tablet

    KW - treatment outcome

    KW - treatment response

    KW - tremor

    KW - vomiting

    KW - animal

    KW - drug effect

    KW - drug tolerance

    KW - Indonesia

    KW - malaria falciparum

    KW - physiology

    KW - Amodiaquine

    KW - Animals

    KW - Antimalarials

    KW - Artemisinins

    KW - Drug Resistance, Multiple

    KW - Drug Tolerance

    KW - Humans

    KW - Malaria, Falciparum

    KW - Malaria, Vivax

    KW - Quinolines

    KW - Sesquiterpenes

    KW - Treatment Outcome

    UR - http://www.scopus.com/inward/record.url?scp=33947499544&partnerID=8YFLogxK

    M3 - Article

    VL - 44

    SP - 1067

    EP - 1074

    JO - Clinical Infectious Diseases

    JF - Clinical Infectious Diseases

    SN - 1058-4838

    IS - 8

    ER -