Therapeutic response to dihydroartemisinin-piperaquine for P. falciparum and P. Vivax nine years after its introduction in southern Papua, Indonesia

Jeanne Rini Poespoprodjo, Enny Kenangalem, Johny Wafom, Freis Chandrawati, Agatha M. Puspitasari, Benedikt Ley, Leily Trianty, Zoe Korten, Asik S. Surya, Din Syafruddin, Nicholas Anstey, Jutta Marfurt, Rintis Noviyanti, Ric Price

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    Abstract

    Dihydroartemisinin–piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence intervals [CI]: 87.4–99.9) in the 61 patients with P. falciparum malaria, and 98.2% [95% CI: 90.3–100] in the 56 patients with P. vivax malaria. By day 2, 98% (56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of plasmepsin 2–3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.
    Original languageEnglish
    Pages (from-to)677-682
    Number of pages6
    JournalAmerican Journal of Tropical Medicine and Hygiene
    Volume98
    Issue number3
    DOIs
    Publication statusPublished - Mar 2018

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    dihydroartemisinin
    Indonesia
    Plasmodium falciparum
    Malaria
    Vivax Malaria
    Plasmodium vivax
    Parasitemia
    Therapeutics
    Parasites
    Confidence Intervals
    Falciparum Malaria
    piperaquine
    Pharmaceutical Preparations
    Tablets

    Cite this

    Poespoprodjo, Jeanne Rini ; Kenangalem, Enny ; Wafom, Johny ; Chandrawati, Freis ; Puspitasari, Agatha M. ; Ley, Benedikt ; Trianty, Leily ; Korten, Zoe ; Surya, Asik S. ; Syafruddin, Din ; Anstey, Nicholas ; Marfurt, Jutta ; Noviyanti, Rintis ; Price, Ric. / Therapeutic response to dihydroartemisinin-piperaquine for P. falciparum and P. Vivax nine years after its introduction in southern Papua, Indonesia. In: American Journal of Tropical Medicine and Hygiene. 2018 ; Vol. 98, No. 3. pp. 677-682.
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    abstract = "Dihydroartemisinin–piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7{\%} (95{\%} confidence intervals [CI]: 87.4–99.9) in the 61 patients with P. falciparum malaria, and 98.2{\%} [95{\%} CI: 90.3–100] in the 56 patients with P. vivax malaria. By day 2, 98{\%} (56/57) of patients with P. falciparum and 96.9{\%} (63/65) of those with P. vivax had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of plasmepsin 2–3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.",
    author = "Poespoprodjo, {Jeanne Rini} and Enny Kenangalem and Johny Wafom and Freis Chandrawati and Puspitasari, {Agatha M.} and Benedikt Ley and Leily Trianty and Zoe Korten and Surya, {Asik S.} and Din Syafruddin and Nicholas Anstey and Jutta Marfurt and Rintis Noviyanti and Ric Price",
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    Therapeutic response to dihydroartemisinin-piperaquine for P. falciparum and P. Vivax nine years after its introduction in southern Papua, Indonesia. / Poespoprodjo, Jeanne Rini; Kenangalem, Enny; Wafom, Johny ; Chandrawati, Freis ; Puspitasari, Agatha M.; Ley, Benedikt; Trianty, Leily; Korten, Zoe; Surya, Asik S.; Syafruddin, Din; Anstey, Nicholas; Marfurt, Jutta; Noviyanti, Rintis; Price, Ric.

    In: American Journal of Tropical Medicine and Hygiene, Vol. 98, No. 3, 03.2018, p. 677-682.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - Therapeutic response to dihydroartemisinin-piperaquine for P. falciparum and P. Vivax nine years after its introduction in southern Papua, Indonesia

    AU - Poespoprodjo, Jeanne Rini

    AU - Kenangalem, Enny

    AU - Wafom, Johny

    AU - Chandrawati, Freis

    AU - Puspitasari, Agatha M.

    AU - Ley, Benedikt

    AU - Trianty, Leily

    AU - Korten, Zoe

    AU - Surya, Asik S.

    AU - Syafruddin, Din

    AU - Anstey, Nicholas

    AU - Marfurt, Jutta

    AU - Noviyanti, Rintis

    AU - Price, Ric

    PY - 2018/3

    Y1 - 2018/3

    N2 - Dihydroartemisinin–piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence intervals [CI]: 87.4–99.9) in the 61 patients with P. falciparum malaria, and 98.2% [95% CI: 90.3–100] in the 56 patients with P. vivax malaria. By day 2, 98% (56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of plasmepsin 2–3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.

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