Skip to main content
Top
Published in: Malaria Journal 1/2015

Open Access 01-12-2015 | Research

Artemether-lumefantrine versus artemisinin-naphthoquine in Papua New Guinean children with uncomplicated malaria: a six months post-treatment follow-up study

Authors: Moses Laman, John M Benjamin, Brioni R Moore, Mary Salib, Somoyang Tawat, Wendy A Davis, Peter M Siba, Leanne J Robinson, Timothy ME Davis

Published in: Malaria Journal | Issue 1/2015

Login to get access

Abstract

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 children with Plasmodium falciparum or Plasmodium vivax compared with 2.2% and 30.0%, respectively, in AM-LM-treated children during 42 days of follow-up. To determine whether, consistent with the long elimination half-life of NQ, this difference in efficacy would be more durable, clinical episodes of malaria were assessed in a subset of trial patients followed for six months post-treatment.

Methods

For children completing trial procedures and who were assessable at six months, all within-trial and subsequent clinical malaria episodes were ascertained, the latter by clinic attendances and/or review of hand-held health records. Presentations with non-malarial illness were also recorded. Differences between allocated treatments for pre-specified endpoints were determined using Kaplan-Meier survival analysis.

Results

Of 247 children who were followed to Day 42, 176 (71.3%) were included in the present sub-study, 87 allocated to AM-LM and 89 to artemisinin-NQ. Twenty children in the AM-LM group (32.8%) had a first episode of clinical malaria within six months compared with 10 (16.4%) in the artemisinin-NQ group (P = 0.033, log rank test). The median (interquartile range) time to first episode of clinical malaria was 64 (50–146) vs 116 (77–130) days, respectively (P = 0.20). There were no between-group differences in the incidence of first presentation with non-malarial illness (P = 0.31).

Conclusions

The greater effectiveness of artemisinin-NQ over conventional AM-LM extends to at least six months post-treatment for clinical malaria but not non-malarial illness.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12610000913​077.
Literature
2.
go back to reference World Health Organization. Global report on antimalarial drug efficacy and drug resistance: 2000–2010. Geneva: WHO; 2010. World Health Organization. Global report on antimalarial drug efficacy and drug resistance: 2000–2010. Geneva: WHO; 2010.
3.
go back to reference World Health Organization. Guidelines for the treatment of malaria. 2nd ed. Geneva: WHO; 2010. World Health Organization. Guidelines for the treatment of malaria. 2nd ed. Geneva: WHO; 2010.
4.
go back to reference Stepniewska K, Taylor WR, Mayxay M, Price R, Smithuis F, Guthmann JP, et al. In vivo assessment of drug efficacy against Plasmodium falciparum malaria: duration of follow-up. Antimicrob Agents Chemother. 2004;48:4271–80.CrossRefPubMedCentralPubMed Stepniewska K, Taylor WR, Mayxay M, Price R, Smithuis F, Guthmann JP, et al. In vivo assessment of drug efficacy against Plasmodium falciparum malaria: duration of follow-up. Antimicrob Agents Chemother. 2004;48:4271–80.CrossRefPubMedCentralPubMed
5.
go back to reference Visser BJ, Wieten RW, Kroon D, Nagel IM, Belard S, van Vugt M, et al. Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review. Malar J. 2014;13:463.CrossRefPubMedCentralPubMed Visser BJ, Wieten RW, Kroon D, Nagel IM, Belard S, van Vugt M, et al. Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review. Malar J. 2014;13:463.CrossRefPubMedCentralPubMed
6.
go back to reference Abbey M, Bartholomew LK, Nonvignon J, Chinbuah MA, Pappoe M, Gyapong M, et al. Factors related to retention of community health workers in a trial on community-based management of fever in children under 5 years in the Dangme West District of Ghana. Int Health. 2014;6:99–105.CrossRefPubMed Abbey M, Bartholomew LK, Nonvignon J, Chinbuah MA, Pappoe M, Gyapong M, et al. Factors related to retention of community health workers in a trial on community-based management of fever in children under 5 years in the Dangme West District of Ghana. Int Health. 2014;6:99–105.CrossRefPubMed
7.
go back to reference Laman M, Moore BR, Benjamin J, Yadi G, Bona C, Warrel J, et al. Artemisinin-naphthoquine versus artemether-lumefantrine for uncomplicated malaria in Papua New Guinean children: An open label randomised trial. PLoS Med. 2014;11:e1001773.CrossRefPubMedCentralPubMed Laman M, Moore BR, Benjamin J, Yadi G, Bona C, Warrel J, et al. Artemisinin-naphthoquine versus artemether-lumefantrine for uncomplicated malaria in Papua New Guinean children: An open label randomised trial. PLoS Med. 2014;11:e1001773.CrossRefPubMedCentralPubMed
8.
go back to reference Ezzet F, Mull R, Karbwang J. Population pharmacokinetics and therapeutic response of CGP 56697 (artemether + benflumetol) in malaria patients. Br J Clin Pharmacol. 1998;46:553–61.CrossRefPubMedCentralPubMed Ezzet F, Mull R, Karbwang J. Population pharmacokinetics and therapeutic response of CGP 56697 (artemether + benflumetol) in malaria patients. Br J Clin Pharmacol. 1998;46:553–61.CrossRefPubMedCentralPubMed
9.
go back to reference Batty KT, Salman S, Moore BR, Benjamin J, Lee ST, Page-Sharp M, et al. Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a pharmacokinetic study. Antimicrob Agents Chemother. 2012;56:2472–84.CrossRefPubMedCentralPubMed Batty KT, Salman S, Moore BR, Benjamin J, Lee ST, Page-Sharp M, et al. Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a pharmacokinetic study. Antimicrob Agents Chemother. 2012;56:2472–84.CrossRefPubMedCentralPubMed
10.
go back to reference Michon P, Cole-Tobian JL, Dabod E, Schoepflin S, Igu J, Susapu M, et al. The risk of malarial infections and disease in Papua New Guinean children. Am J Trop Med Hyg. 2007;76:997–1008.PubMedCentralPubMed Michon P, Cole-Tobian JL, Dabod E, Schoepflin S, Igu J, Susapu M, et al. The risk of malarial infections and disease in Papua New Guinean children. Am J Trop Med Hyg. 2007;76:997–1008.PubMedCentralPubMed
11.
go back to reference Cattani JA, Tulloch JL, Vrbova H, Jolley D, Gibson FD, Moir JS, et al. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg. 1986;35:3–15.PubMed Cattani JA, Tulloch JL, Vrbova H, Jolley D, Gibson FD, Moir JS, et al. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg. 1986;35:3–15.PubMed
12.
go back to reference World Health Organization. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. Geneva: WHO; 2003. World Health Organization. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. Geneva: WHO; 2003.
13.
go back to reference Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of MSP-1, MSP-2, and GLURP. Am J Trop Med Hyg. 2003;68:133–9.PubMed Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of MSP-1, MSP-2, and GLURP. Am J Trop Med Hyg. 2003;68:133–9.PubMed
14.
go back to reference Felger I, Beck HP. Genotyping of Plasmodium falciparum. PCR-RFLP analysis. Methods Mol Med. 2002;72:117–29.PubMed Felger I, Beck HP. Genotyping of Plasmodium falciparum. PCR-RFLP analysis. Methods Mol Med. 2002;72:117–29.PubMed
15.
go back to reference Barnadas C, Koepfli C, Karunajeewa HA, Siba PM, Davis TM, Mueller I. Characterization of treatment failure in efficacy trials of drugs against Plasmodium vivax by genotyping neutral and drug resistance-associated markers. Antimicrob Agents Chemother. 2011;55:4479–81.CrossRefPubMedCentralPubMed Barnadas C, Koepfli C, Karunajeewa HA, Siba PM, Davis TM, Mueller I. Characterization of treatment failure in efficacy trials of drugs against Plasmodium vivax by genotyping neutral and drug resistance-associated markers. Antimicrob Agents Chemother. 2011;55:4479–81.CrossRefPubMedCentralPubMed
17.
go back to reference Laman M, Moore BR, Benjamin J, Padapu N, Tarongka N, Siba P, et al. Comparison of an assumed versus measured leucocyte count in parasite density calculations in Papua New Guinean children with uncomplicated malaria. Malar J. 2014;13:145.CrossRefPubMedCentralPubMed Laman M, Moore BR, Benjamin J, Padapu N, Tarongka N, Siba P, et al. Comparison of an assumed versus measured leucocyte count in parasite density calculations in Papua New Guinean children with uncomplicated malaria. Malar J. 2014;13:145.CrossRefPubMedCentralPubMed
18.
go back to reference Paediatrics Society of PNG. Standard Treatment for common illnesses of children in PNG. 9th edition. Port Moresby 2011. Paediatrics Society of PNG. Standard Treatment for common illnesses of children in PNG. 9th edition. Port Moresby 2011.
19.
go back to reference Wong RP, Salman S, Ilett KF, Siba PM, Mueller I, Davis TM. Desbutyl-lumefantrine is a metabolite of lumefantrine with potent in vitro antimalarial activity that may influence artemether-lumefantrine treatment outcome. Antimicrob Agents Chemother. 2011;55:1194–8.CrossRefPubMedCentralPubMed Wong RP, Salman S, Ilett KF, Siba PM, Mueller I, Davis TM. Desbutyl-lumefantrine is a metabolite of lumefantrine with potent in vitro antimalarial activity that may influence artemether-lumefantrine treatment outcome. Antimicrob Agents Chemother. 2011;55:1194–8.CrossRefPubMedCentralPubMed
20.
go back to reference Graham SM, Molyneux EM, Walsh AL, Cheesbrough JS, Molyneux ME, Hart CA. Nontyphoidal Salmonella infections of children in tropical Africa. Pediatr Infect Dis J. 2000;19:1189–96.CrossRefPubMed Graham SM, Molyneux EM, Walsh AL, Cheesbrough JS, Molyneux ME, Hart CA. Nontyphoidal Salmonella infections of children in tropical Africa. Pediatr Infect Dis J. 2000;19:1189–96.CrossRefPubMed
21.
go back to reference Manning L, Laman M, Rosanas-Urgell A, Michon P, Aipit S, Bona C, et al. Severe anemia in Papua New Guinean children from a malaria-endemic area: a case–control etiologic study. PLoS Negl Trop Dis. 2012;6:e1972.CrossRefPubMedCentralPubMed Manning L, Laman M, Rosanas-Urgell A, Michon P, Aipit S, Bona C, et al. Severe anemia in Papua New Guinean children from a malaria-endemic area: a case–control etiologic study. PLoS Negl Trop Dis. 2012;6:e1972.CrossRefPubMedCentralPubMed
22.
go back to reference Walsh AL, Phiri AJ, Graham SM, Molyneux EM, Molyneux ME. Bacteremia in febrile Malawian children: clinical and microbiologic features. Pediatr Infect Dis J. 2000;19:312–8.CrossRefPubMed Walsh AL, Phiri AJ, Graham SM, Molyneux EM, Molyneux ME. Bacteremia in febrile Malawian children: clinical and microbiologic features. Pediatr Infect Dis J. 2000;19:312–8.CrossRefPubMed
23.
go back to reference Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, et al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis. 2009;49:1629–37.CrossRefPubMed Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, et al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis. 2009;49:1629–37.CrossRefPubMed
24.
go back to reference Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, et al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One. 2008;3:e2390.CrossRefPubMedCentralPubMed Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, et al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One. 2008;3:e2390.CrossRefPubMedCentralPubMed
25.
go back to reference Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, et al. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg. 2006;75:219–25.PubMed Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, et al. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg. 2006;75:219–25.PubMed
26.
go back to reference Stepniewska K, White NJ. Pharmacokinetic determinants of the window of selection for antimalarial drug resistance. Antimicrob Agents Chemother. 2008;52:1589–96.CrossRefPubMedCentralPubMed Stepniewska K, White NJ. Pharmacokinetic determinants of the window of selection for antimalarial drug resistance. Antimicrob Agents Chemother. 2008;52:1589–96.CrossRefPubMedCentralPubMed
27.
go back to reference Watkins WM, Sibley CH, Hastings IM. The search for effective and sustainable treatments for Plasmodium falciparum malaria in Africa: a model of the selection of resistance by antifolate drugs and their combinations. Am J Trop Med Hyg. 2005;72:163–73.PubMed Watkins WM, Sibley CH, Hastings IM. The search for effective and sustainable treatments for Plasmodium falciparum malaria in Africa: a model of the selection of resistance by antifolate drugs and their combinations. Am J Trop Med Hyg. 2005;72:163–73.PubMed
28.
go back to reference Al-Yaman F, Genton B, Mokela D, Narara A, Raiko A, Alpers MP. Resistance of Plasmodium falciparum malaria to amodiaquine, chloroquine and quinine in the Madang Province of Papua New Guinea, 1990–1993. P N G Med J. 1996;39:16–22.PubMed Al-Yaman F, Genton B, Mokela D, Narara A, Raiko A, Alpers MP. Resistance of Plasmodium falciparum malaria to amodiaquine, chloroquine and quinine in the Madang Province of Papua New Guinea, 1990–1993. P N G Med J. 1996;39:16–22.PubMed
29.
go back to reference Shanks GD, Edstein MD, Jacobus D. Evolution from double to triple-antimalarial drug combinations. Trans R Soc Trop Med Hyg. 2014;109:182–8.CrossRefPubMed Shanks GD, Edstein MD, Jacobus D. Evolution from double to triple-antimalarial drug combinations. Trans R Soc Trop Med Hyg. 2014;109:182–8.CrossRefPubMed
Metadata
Title
Artemether-lumefantrine versus artemisinin-naphthoquine in Papua New Guinean children with uncomplicated malaria: a six months post-treatment follow-up study
Authors
Moses Laman
John M Benjamin
Brioni R Moore
Mary Salib
Somoyang Tawat
Wendy A Davis
Peter M Siba
Leanne J Robinson
Timothy ME Davis
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2015
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-015-0624-4

Other articles of this Issue 1/2015

Malaria Journal 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.