The online version of this article (doi:10.1186/1475-2875-11-153) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
ET: study conceptualization and design. ET, ARH, HS, BP, RE, EAY, TP, SL, ES, N, EY, LY, JL, BW, FA, TADD, AP performed the study. ET, ARH, HS and ES analysed the data. ET, ARH, ES, T prepared the manuscript. All authors have read and approved the final manuscript.
A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN) with a three-day regimen of dihydroartemisinin-piperaquine (DHP), the existing programme drug, in adults with uncomplicated symptomatic malaria.
This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR) uncorrected and corrected.
There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 ± 11.7 hours vs 25.5 ± 12.2 hours, p = 0.04). There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3–97.2) and 96.3% (95% Cl: 93.6–99.0) in AN, 96.3% (95% Cl: 93.5–99.0) and 97.3% (95% Cl: 95.0–99.6) in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality.
AN and DHP are confirmed very effective, safe and tolerate for treatment of any malaria. Both drugs are promising for multiple first-line therapy policies in Indonesia.
Authors’ original file for figure 112936_2012_2099_MOESM1_ESM.gif
Authors’ original file for figure 212936_2012_2099_MOESM2_ESM.gif
Authors’ original file for figure 312936_2012_2099_MOESM3_ESM.gif
Authors’ original file for figure 412936_2012_2099_MOESM4_ESM.gif
Authors’ original file for figure 512936_2012_2099_MOESM5_ESM.gif
Authors’ original file for figure 612936_2012_2099_MOESM6_ESM.gif
Authors’ original file for figure 712936_2012_2099_MOESM7_ESM.gif
World Health Organization: World Malaria Report 2008. WHO/HTM/GMP/2008.1. 2008, WHO, Geneva
World Health Organization: Antimalarial drug combination therapy. 2001, WHO, Geneva
Nosten F, van Vugt M, Price RN, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looareesuwan S, White NJ: Effects of artesunate-mefloquine combination on incidence ofPlasmodium falciparummalaria and mefloquine resistance in western Thailand: a prospective study. Lancet. 2000, 356: 297-302. 10.1016/S0140-6736(00)02505-8. CrossRefPubMed
Tjitra E, Gunawan S, Laihad F, Marwoto H, Sulaksono S, Arjoso S, Richie TL, Manurung N: Evaluation of antimalaria drugs in Indonesia, 1981–1995. Bull Hlth Studies. 1997, 25: 27-58.
Hasugian AR, Purba HLE, Kenangalem E, Wuwung RM, Ebsworth EP, Maristela R, Penttinen PMP, Laihad F, Anstey NM, Tjitra E, Price RN: Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistantPlasmodium falciparumandPlasmodium vivaxmalaria. Clin Infect Dis. 2007, 44: 1067-1074. 10.1086/512677. PubMedCentralCrossRefPubMed
Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, Ebsworth EP, Anstey NM, Tjitra E, Price RN: Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet. 2007, 369: 757-765. 10.1016/S0140-6736(07)60160-3. PubMedCentralCrossRefPubMed
Pang X, Wang G, Xing Q: Hundred one casesPlasmodium falciparumtreated with naphthoquine phosphate. Chinese J Parasitic Disease. 1999, 17: 20-22.
Wang JY, Shan CQ, Fu D: Clinical trial of co-naphthoquine in the treatment of falciparum malaria. Chin J Parasit Dis Con. 2003, 16: 135-136.
Guo WZ, Zheng Q, Li G, Guo XB: A randomized controlled study of napthoquine and artesunate in the treatment of falciparum malaria. Journal of Guangzhou University Traditional Chinese Medicine. 2003, 17: 235-237.
World Health Organization: Guidelines for the treatment of malaria. WHO/HTM/MAL/2006.1108. 2006, WHO, Geneva
Schulz KF, Grimes DA: The Lancet Handbook of Essential Concepts in Clinical Research. Main edition. 2006, Elsevier, Edinburg, London, New York, Oxford, Philadelphia, St Louis, Sydney, Toronto
World Health Organization: Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. 2003, WHO, Geneva
World Health Organization: Methods and techniques for clinical trials on antimalarial drug efficacy. Genotyping to identify parasite populations. Informal consultation organized by the Medicines for Malaria Venture and cosponsored by the World Health Organization. 29–31 May 2007. 2008, WHO, Amsterdam, The Netherlands
Monitoring and Reporting Adverse Events. World Health Organization: Toxicity Grading Scale for Determining Severity of Adverse Events. 2003, , , [ http://icssc.org/documents/AE%20Manual%202003%20Appendices%20February_06_2003%20final.pdf]
Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WRJ: Amodiaquine-artesunate versus amodiaquine for uncomplicatedPlasmodium falciparummalaria in African children: a randomised, multicentre trial. Lancet. 2002, 359: 1365-1372. 10.1016/S0140-6736(02)08348-4. CrossRefPubMed
World Health Organization: The use of artemisinin and its derivatives as antimalarial drugs: report of a joint CTD/DMP/TDR Informal Consultation, WHO/MAL/98.1086. 1998, WHO, Geneva
Watkins WM, Sibley CH, Hastings IM: The search for effective and sustainable treatment forPlasmodium falciparummalaria in Africa: a model of the selection of resistance by antifolate drugs and their combinations. AmJTrop Med Hyg. 2005, 72: 163-173.
Hombhanje FW, Linge D, Saweri A, Kuanch C, Jones R, Toraso S, Geita J, Masta A, Kevau I, Hiawalyer G, Sapuri M: Artemisinin-naphthoquine combination (ARCOTM) therapy for uncomplicated falciparum malaria in adults of Papua New Guinea: a preliminary report on safety and efficacy. Malar J. 2009, 8: 196-10.1186/1475-2875-8-196. PubMedCentralCrossRefPubMed
Tran TH, Dolecek C, Pham PM, Nguyen TD, Nguyen TT, Le HT, Dong THA, Tran TT, Stepniewska K, White NJ, Farrar J: Dihydroartemisinin-piperaquine against multidrug-resistantPlasmodium falciparummalaria in Vietnam: randomized clinical trial. Lancet. 2004, 363: 18-22. 10.1016/S0140-6736(03)15163-X. CrossRefPubMed
Ashley EA, Krudsood S, Phaiphun L, Srivilairit S, McGready R, Leowattana W, Hutagalung R, Wilairatana P, Brockman A, Looareesuwan S, Nosten F, White NJ: Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. J Infect Dis. 2004, 190: 1773-1782. 10.1086/425015. CrossRefPubMed
Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo APP, Naing AL, Nyo MY, Myint NZH, Imwong M, Ashley E, Lee SJ, White NJ: Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria an open-label randomized comparison. Lancet. 2006, 367: 2075-2085. 10.1016/S0140-6736(06)68931-9. CrossRefPubMed
Mayxay M, Thongpraseuth V, Khanthavong M, Lindegardh N, Barends M, Keola S, Pongvongsa T, Phompida S, Phetsouvanh R, Stepniewska K, White NJ, Newton PN: An open, randomized comparison of artesunate plus mefloquine vs dihydroartemisinin-piperaquine for the treatment of uncomplicatedPlasmodium falciparummalaria in the Lao People’s Democratic Republic (Laos). Trop Med Int Health. 2006, 11: 1157-1165. 10.1111/j.1365-3156.2006.01671.x. CrossRefPubMed
Shanks GD, Wilairatanaporn C: Eosinophilic response to falciparum malaria infections. Southeast Asian J Trop Med Public Health. 1992, 23: 795-797. PubMed
Wang JY, Sun ZW, Fu DD: Efficacy of naphthoquine, artemisinin and combination of the two drugs in the treatment of falciparum malaria. Clin J Parasitic Dis. 2003, 21: 131-133.
Toure OA, Penali LK, Yapi JD, Ako BA, Toure W, Djerea K, Gomez GO, Makaila O: A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one dayversusartemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d’Ivoire. Malar J. 2009, 8: 148-10.1186/1475-2875-8-148. PubMedCentralCrossRefPubMed
Benyamin J, Moore B, Lee ST, Senn M, Griffin S, Lautu D, Salman S, Siba P, Mueller I, Davis TM: Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a tolerability, safety, and preliminary efficacy study. Antimicrob Agents Chemother. 2012, 56: 2465-2471. 10.1128/AAC.06248-11. CrossRef
- Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia
Armedy R Hasugian
Endah A Yusnita
Tersila AD Dedang
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II