Artemisinin-Naphthoquine versus Artemether-Lumefantrine for Uncomplicated Malaria in Papua New Guinean Children: An Open-Label Randomized Trial
MetadataShow full item record
This open access article is distributed under the Creative Commons licensehttps://creativecommons.org/licenses/by/4.0/
© 2014 Laman et al. Artemisinin combination therapies (ACTs) with broad efficacy are needed where multiple Plasmodium species are transmitted, especially in children, who bear the brunt of infection in endemic areas. In Papua New Guinea (PNG), artemether-lumefantrine is the first-line treatment for uncomplicated malaria, but it has limited efficacy against P. vivax. Artemisinin-naphthoquine should have greater activity in vivax malaria because the elimination of naphthoquine is slower than that of lumefantrine. In this study, the efficacy, tolerability, and safety of these ACTs were assessed in PNG children aged 0.5–5 y.An open-label, randomized, parallel-group trial of artemether-lumefantrine (six doses over 3 d) and artemisinin-naphthoquine (three daily doses) was conducted between 28 March 2011 and 22 April 2013. Parasitologic outcomes were assessed without knowledge of treatment allocation. Primary endpoints were the 42-d P. falciparum PCR-corrected adequate clinical and parasitologic response (ACPR) and the P. vivax PCR-uncorrected 42-d ACPR. Non-inferiority and superiority designs were used for falciparum and vivax malaria, respectively. Because the artemisinin-naphthoquine regimen involved three doses rather than the manufacturer-specified single dose, the first 188 children underwent detailed safety monitoring. Of 2,542 febrile children screened, 267 were randomized, and 186 with falciparum and 47 with vivax malaria completed the 42-d follow-up. Both ACTs were safe and well tolerated. P. falciparum ACPRs were 97.8% and 100.0% in artemether-lumefantrine and artemisinin-naphthoquine-treated patients, respectively (difference 2.2% [95% CI -3.0% to 8.4%] versus -5.0% non-inferiority margin, p?=?0.24), and P. vivax ACPRs were 30.0% and 100.0%, respectively (difference 70.0% [95% CI 40.9%–87.2%], p<0.001). Limitations included the exclusion of 11% of randomized patients with sub-threshold parasitemias on confirmatory microscopy and direct observation of only morning artemether-lumefantrine dosing.Artemisinin-naphthoquine is non-inferior to artemether-lumefantrine in PNG children with falciparum malaria but has greater efficacy against vivax malaria, findings with implications in similar geo-epidemiologic settings within and beyond Oceania.Australian New Zealand Clinical Trials Registry ACTRN12610000913077.Please see later in the article for the Editors' Summary.
Showing items related by title, author, creator and subject.
Gametocyte clearance kinetics determined by quantitative magnetic fractionation in Melanesian children with uncomplicated malaria treated with artemisinin combination therapyKarl, S.; Laman, M.; Moore, Brioni; Benjamin, J.; Koleala, T.; Ibam, C.; Kasian, B.; Siba, P.; Waltmann, A.; Mueller, I.; Woodward, R.; St Pierre, T.; Davis, T. (2015)Copyright © 2015, American Society for Microbiology. All Rights Reserved.Quantitative magnetic fractionation and a published mathematical model were used to characterize between-treatment differences in gametocyte density ...
Artemether-lumefantrine versus artemisinin-naphthoquine in Papua New Guinean children with uncomplicated malaria: A six months post-treatment follow-up studyLaman, M.; Benjamin, J.; Moore, Brioni; Salib, M.; Tawat, S.; Davis, W.; Siba, P.; Robinson, L.; Davis, T. (2015)Background: In a recent trial of artemisinin-naphthoquine (artemisinin-NQ) and artemether-lumefantrine (AM-LM) therapy in young children from Papua New Guinea (PNG), there were no treatment failures in artemisinin-NQ-treated ...
Risk factors for Plasmodium falciparum and Plasmodium vivax gametocyte carriage in Papua New Guinean children with uncomplicated malariaKarl, S.; Laman, M.; Moore, Brioni; Benjamin, J.; Salib, M.; Lorry, L.; Maripal, S.; Siba, P.; Robinson, L.; Mueller, I.; Davis, T. (2016)© 2016.There are limited data on gametocytaemia risk factors before/after treatment with artemisinin combination therapy in children from areas with transmission of multiple Plasmodium species. We utilised data from a ...