Dose Ranging Studies of New Artemisinin-Piperaquine Fixed Combinations Compared to Standard Regimens.
By Artemisinin Combination Therapies For Acute Uncomplicated Falciparum Malaria. Srivicha Krudsood1,
Noppadon Tangpukdee1, Vipa Thanchatwet1, Polrat Wilairatana1, Siripan Srivilairit1, Nantaporn Pothipak1,
Song Jianping2, Li Guoqiao2, Gary M Brittenham3 and Sornchai Looareesuwan1
Abstract: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 2Guangzhou
University of Traditional Chinese Medicine, Guangzhou, PR China; 3Pediatrics and Medicine (GMB), Columbia
University College of Physicians and Surgeons, New York, USA Abstract. To determine the optimum dose of
artemisinin-piperaquine combination therapies for acute uncomplicated Plasmodium falciparum malaria, we
examined 7 candidate regimens in 411 patients admitted to the Bangkok Hospital for Tropical Diseases. The
studies were performed from May 2005 to October 2005 and November 2005 to June 2006. We compared 3-day
courses of artesunate-mefloquine, artemether-lumefantrine (Coartem®) and of dihydroartemisinin-piperaquine
(Artekin®) as reference antimalarial treatments, with candidate regimens using 2-3 day courses of
artemisinin-piperaquine, Artequick®. Initially, patients receiving each of the regimens had a rapid clinical
and parasitological response. All treatments were well tolerated and no serious adverse effects occurred.
The 28-day cure rates were <80% for the 2-day treatments with artemisinin-piperaquine at 2.4 mg/kg
and 14.4 mg/kg, respectively, in the first study period and artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg,
respectively, but >98% for the 3-day regimens. These results suggest that a 3-day course of
artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, deserve further evaluation as an
alternative treatment for multidrug-resistant P. falciparum malaria.
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By Chantal M Morel, Jeremy A Lauer, David B Evans. This article is part of a series examining the cost
effectiveness of strategies to achieve the millennium development goals for health.
Abstract: Objective: To determine the cost effectiveness of selected malaria
control interventions in the context of reaching the millennium development goals for malaria.
Design: Generalised cost effectiveness analysis.
Data Sources: Efficacy data came from the literature and authors’ calculations supported by expert
opinion. Quantities for resource inputs came from the literature and from expert opinion; prices came from the WHO-CHOICE database.
Methods: Costs were assessed in year 2000 international dollars, and effects were assessed as disability adjusted
life years averted by a 10 year implementation programme. Analysis was restricted to sub-Saharan regions where the most
deadly form of malaria, Plasmodium falciparum, is most prevalent. The impact on population health for various interventions,
and their combinations, was evaluated at selected coverage levels by using a state-transition model. Sensitivity
analysis was done for age weights and discounting.
Results: High coverage with artemisinin based combination treatments was found to be the most cost
effective strategy for control of malaria in most countries in sub-Saharan Africa.
Conclusions: A much larger infusion of resources than those currently available is needed to
make headway in the fight to rollback malaria. On cost effectiveness grounds, in most areas in sub-Saharan
Africa greater coverage with highly effective combination treatments should be the cornerstone of malaria
control. However, treatment alone can achieve less than half the total benefit obtainable through a
combination of interventions —scaling up the use of impregnated mosquito nets or indoors praying with
insecticides is also critical. Intermittent presumptive treatment of pregnant women can bring as mall
but important additional health gain at relatively low-cost.
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By Noppadon Tangpukdee1, Srivicha Krudsood1, Vipa Thanachartwet1, Chaweewan Pengruksa1, Nanthaporn Phophak1, Shigeyuki Kano2,
Guoqiao Li3, Gary M Brittenham4, Sornchai Looareesuwan1* and Polrat Wilairatana1,5
Abstract: To determine the efficacy, safety and tolerability of an alternative short-course,
artemisinin-based combination therapy for acute uncomplicated Plasmodium falciparum malaria, we compared
Artequick®–a fixed-dosed combination of artemisinin (80 mg), piperaquine (400 mg), and primaquine (4 mg),
per tablet–with a standard regimen of artesunate-mefloquine. A total of 130 patients were randomly
assigned to treatment with an orally administered, once-daily, 3-day regimen of either Artequick®
(Group A: 3.2 mg/kg/day of artemisinin, 16 mg/kg/ day of piperaquine, and 0.16 mg/kg/day of primaquine)
or artesunate-mefloquine (Group B: artesunate, 4 mg/kg/day, with mefloquine, 8 mg/kg/day). Patients
receiving each regimen had a rapid clinical and parasitological response. All treatments were well
tolerated, and no serious adverse effects occurred. No significant differences were found in fever- and
parasite-clearance times between the two study groups. The 28-day cure rates were similarly high,
at 98.5% and 100%, in groups A and B, respectively. We conclude that Artequick® was as effective and
well tolerated as artesunate-mefloquine and could be used as an alternative treatment for
multidrug-resistant Plasmodium falciparum malaria in Southeast Asia.
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Dose ranging studies of new artemisinin-piperaquine fixed combinations compared to standard regimens of artemisisnin combination therapies for acute uncomplicated falciparum malaria.
Krudsood S, Tangpukdee N, Thanchatwet V, Wilairatana P, Srivilairit S, Pothipak N, Jianping S, Guoqiao L, Brittenham GM, Looareesuwan S.
Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Bangkok 10400, Thailand. tmsks@mahidol.ac.th
To determine the optimum dose of artemisinin-piperaquine combination therapies for acute uncomplicated Plasmodium falciparum malaria, we examined 7 candidate regimens in 411 patients admitted to the Bangkok Hospital for Tropical Diseases. The studies were performed from May 2005 to October 2005 and November 2005 to June 2006. We compared 3-day courses of artesunate-mefloquine, artemether-lumefantrine (Coartem) and of dihydroartemisinin-piperaquine (Artekin) as reference antimalarial treatments, with candidate regimens using 2-3 day courses of artemisinin-piperaquine, Artequick. Initially, patients receiving each of the regimens had a rapid clinical and parasitological response. All treatments were well tolerated and no serious adverse effects occurred. The 28-day cure rates were < 80% for the 2-day treatments with artemisinin-piperaquine at 2.4 mg/kg and 14.4 mg/kg, respectively, in the first study period and artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, but > 98% for the 3-day regimens. These results suggest that a 3-day course of artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg, respectively, deserve further evaluation as an alternative treatment for multidrug-resistant P. falciparum malaria. MORE
A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria.
Trung TN, Tan B, Van Phuc D, Song JP.
Institute of Malariology, Parasitology and Entomology-Qui Nhon, Ministry of Health, Vietnam.
OBJECTIVE: The study aimed to evaluate and compare the efficacy and safety of dihydroartemisinin-piperaquine phosphate (Artekin) and artemisinin-piperaquine (Artequick) in the treatment of uncomplicated falciparum malaria. METHODS: A total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups: 52 cases in the Artequick group, and 51 cases in the Artekin group. The patients in the Artequick group were administered with Artequick, twice in 24 h, whereas the patients in the Artekin group were given Artekin 4 times in 2 days. The mean parasite clearance time, mean fever clearance time, 28-day cure rate and parasite recrudescence rates of the two groups were then compared. RESULTS: The mean parasite clearance time and the mean fever clearance time were 43.2+/-13.9 h and 24.7+/-9.9 h, in the Artequick group, and 36.5+/-17.1 h and 22.7+/-11.2 h, in the Artekin group. In both groups the 28-day cure rate was 100%, and the parasite recrudescence rate was 0. CONCLUSION: Both medicines had high cure rates, low recrudescence rates, and no serious adverse reactions. The administration of Artequick, however, was more convenient and lower incidence of gastrointestinal side effects than that of Artekin, so as to increase the efficacy in the malaria population. MORE