Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis.
Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis.
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DOI：
10.1371/journal.pone.0006358
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发表时间：
2009-07-29
期刊：
影响因子：
3.7
通讯作者：
Nosten F
中科院分区：
文献类型：
--
作者：
Zwang J;Ashley EA;Karema C;D'Alessandro U;Smithuis F;Dorsey G;Janssens B;Mayxay M;Newton P;Singhasivanon P;Stepniewska K;White NJ;Nosten F
固定剂量的双氢青蒿素-哌喹(DP)联合抗疟疾是一种很有前途的青蒿素类联合疗法(ACT)。我们提供了一个关于急性无并发症恶性疟疾的疗效和耐受性的个体患者数据分析，这些数据来自于在非洲和东南亚使用预定义的体内方案进行的7个已发表的随机临床试验。参比药物是泰国、缅甸、老挝和柬埔寨的甲氟喹-青蒿琥酯(MAS3)；乌干达的蒿甲醚-鲁米芬曲宁；卢旺达的阿莫地喹+磺胺多辛-乙胺和青蒿琥酯+阿莫地喹。总共有3547名患者入选：1814名患者(32%的5岁以下儿童)接受了DP治疗，1733名患者接受了12个不同地点的对照抗疟药物治疗，并进行了28-63天的随访。试验之间没有显著的异质性。DP耐受性良好，早期呕吐发生率为1.7%。除腹泻外，儿童和成人使用DP的不良事件均低于MAS3，OR值(95%CI)分别为2.74(2.13~3.51)和3.11(2.31~4.18)。DP治疗可使发热和寄生虫血症迅速消失。生存分析显示，DP28天的PCR型校正有效率为98.7%(95%可信区间为97.6~99.8)。DP在预防恶性疟复发和复发方面均优于对照药物(P = 0.001，按部位加权)。DP和MAS3在治疗间日疟原虫合并感染和抑制首次复发方面没有差异(间日疟原虫复发的中位间隔：6周)。5岁以下儿童这两种感染的复发风险更高。配子细胞血症患者的比例(P = 0.002，按部位加权)和随后的配子体携带率，DP(11/1000人配子细胞周)高于MAS3(6/1000PGW，P = 0.001，按部位加权)。在亚洲和非洲，DP被证明是一种安全、耐受性好和高效的治疗恶性疟原虫的药物，但对配子体携带的效果不如MAS3。
The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new artemisinin-based combination therapy (ACT). We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda. In total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28–63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; ORs (95%CI) 2.74 (2.13 to 3.51) and 3.11 (2.31 to 4.18), respectively. DP treatment resulted in a rapid clearance of fever and parasitaemia. The PCR genotype corrected efficacy at Day 28 of DP assessed by survival analysis was 98.7% (95%CI 97.6–99.8). DP was superior to the comparator drugs in protecting against both P.falciparum recurrence and recrudescence (P = 0.001, weighted by site). There was no difference between DP and MAS3 in treating P. vivax co-infections and in suppressing the first relapse (median interval to P. vivax recurrence: 6 weeks). Children under 5 y were at higher risk of recurrence for both infections. The proportion of patients developing gametocytaemia (P = 0.002, weighted by site) and the subsequent gametocyte carriage rates were higher with DP (11/1000 person gametocyte week, PGW) than MAS3 (6/1000 PGW, P = 0.001, weighted by site). DP proved a safe, well tolerated, and highly effective treatment of P.falciparum malaria in Asia and Africa, but the effect on gametocyte carriage was inferior to that of MAS3.
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影响因子：
3
作者：
Mens, Petra F.;Sawa, Patrick;van Amsterdam, Sandra M.;Versteeg, Inge;Omar, Sabah A.;Schallig, Henk D. F. H.;Kager, Piet A.
通讯作者：
Kager, Piet A.
影响因子：
6.4
作者：
Imwong, Mallika;Snounou, Georges;White, Nicholas J.
通讯作者：
White, Nicholas J.
DOI：
10.1371/journal.pctr.0020020
发表时间：
2007-05-18
期刊：
PLoS clinical trials
影响因子：
--
作者：
Kamya, Moses R;Yeka, Adoke;Dorsey, Grant
通讯作者：
Dorsey, Grant
影响因子：
4.9
作者：
Price, R. N.;Hasugian, A. R.;Tjitra, E.
通讯作者：
Tjitra, E.
影响因子：
6.4
作者：
Ashley, EA;Krudsood, S;White, NJ
通讯作者：
White, NJ