Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Eastern Cambodia
| Autor: | Melissa Mairet-Khedim, Denis Mey Bouth, Maria Dorina Bustos, Huch Chea, Nimol Khim, Rithea Leang, Pascal Ringwald, Rekol Huy, Benoit Witkowski |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Primaquine 030231 tropical medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine parasitic diseases medicine Pharmacology (medical) Artemisinin Adverse effect Prospective cohort study Pharmacology Pyronaridine 0303 health sciences biology 030306 microbiology business.industry Plasmodium falciparum medicine.disease biology.organism_classification Infectious Diseases chemistry Artesunate business Malaria medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 63 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.02242-18 |
| Popis: | In Cambodia, multidrug-resistant Plasmodium falciparum undermines the treatment of uncomplicated malaria, and new therapeutic options are needed. Pyronaridine-artesunate has not previously been evaluated in eastern Cambodia. We conducted a single-arm, open-label, prospective study between July and December 2017 at the Koh Gnek (Mondulkiri) and Veun Sai (Rattanakiri) health centers in eastern Cambodia. Eligible patients were aged ≥7 years (females, ages 12 to 18 years, were excluded), weighing ≥20 kg, with microscopically confirmed P. falciparum monoinfection and fever. Oral pyronaridine-artesunate was administered once daily for 3 days, dosed according to body weight, plus a single dose of primaquine on day 0. Sixty patients were recruited to Koh Gnek, and 61 patients were recruited to Veun Sai. The primary outcomes, i.e., the day 42 PCR-adjusted adequate clinical and parasitological responses (ACPRs), were 98.3% (95% confidence interval [CI], 88.4 to 99.8) in Koh Gnek and 96.7% (95% CI, 87.3 to 99.2) in Veun Sai (Kaplan-Meier). In a per-protocol analysis, the proportions of patients with day 42 PCR-adjusted ACPRs were 98.3% (57/58; 95% CI, 90.8 to 100.0) at Koh Gnek and 96.7% (58/60; 95% CI, 88.5 to 99.6) at Veun Sai. The Kelch13 (C580Y) mutation was present in 70.0% (77/110) of isolates. The copy numbers were increased in 61.3% (73/119) of isolates for Pfpm2 and in 1.7% (2/119) for Pfmdr1 There was no relationship between outcome and the 50% inhibitory concentration of pyronaridine. Adverse events were consistent with malaria, and there were no serious adverse events. Pyronaridine-artesunate has high efficacy in eastern Cambodia and could be used to increase the diversity of antimalarial therapy in the region. (This study is registered in the Australian New Zealand Clinical Trials Registry [ANZCTR] under no. ACTRN12618001300268.). |
| Databáze: | OpenAIRE |
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