NDLI: Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia

Content Provider	Springer Nature : BioMed Central
Author	Nelwan, Erni J. Ekawati, Lenny L. Tjahjono, Bagus Setiabudy, Rianto Sutanto, Inge Chand, Krisin Ekasari, Tyas Djoko, Dwi Basri, Hasan Taylor, W. Robert Duparc, Stephan Subekti, Decy Elyazar, Iqbal Noviyanti, Rintis Sudoyo, Herawati Baird, J. Kevin
Abstract	Background Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy. A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide. Methods During March to July 2013, an open-label, randomized trial enrolled Indonesian soldiers with vivax malaria at Sragen, Central Java, after six months duty in malarious Papua, Indonesia. No malaria transmission occurred at the study site and P. vivax recurrences in the 12 months following therapy were classified as relapses. A historic relapse control derived from a cohort of soldiers who served in the same area of Papua was applied to estimate risk of relapse among randomized treatment groups. Those were: 1) AS followed 2d later by PQ (0.5 mg/kg daily for 14d); 2) co-formulated AS-PYR concurrent with the same regimen of PQ; or 3) co-formulated DHA-PP concurrent with the same regimen of PQ. Results Among 532 soldiers, 219 had vivax malaria during the four months following repatriation to Java; 180 of these were otherwise healthy and G6PD-normal and enrolled in the trial. Subjects in all treatment groups tolerated the therapies well without untoward events and cleared parasitemia within three days. First relapse appeared at day 39 post-enrollment, and the last at day 270. Therapeutic efficacy of PQ against relapse by incidence density analysis was 92 % (95 %CI = 83–97 %), 94 %(95 %CI = 86–97 %), and 95 %(95 %CI = 88–98 %) when combined with AS, AS-PYR, or DHA-PP, respectively. Conclusions This trial offers evidence of good tolerability and efficacy of PQ against P. vivax relapse when administered concurrently with DHA-PP or AS-PYR. These offer alternative partner drugs for radical cure with primaquine. The AS arm demonstrated efficacy with a total dose of 7 mg/kg PQ without concurrently administered blood schizontocide, another option when primaquine therapy is removed in time from the treatment of the acute malaria or applied presumptively without an attack. Trial registration Current Controlled Trials ISRCTN82366390 , assigned 20 March 2013.
Related Links	https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-015-0535-9.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	17417015
DOI	10.1186/s12916-015-0535-9
Journal	BMC Medicine
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2015-12-11
Access Restriction	Open
Subject Keyword	Medicine Public Health Biomedicine Plasmodium vivax Malaria Relapse Primaquine Efficacy Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	7.1/2023
5-Year Journal Impact Factor	8.8/2023

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