Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Infect Dis. 2013 Jun 1;207(11):1655-63. doi: 10.1093/infdis/jit082. Epub 2013 Feb 28.
Artemisinin resistance, a long parasite clearance half-life in response to artemisinin, has been described in patients with Plasmodium falciparum malaria in southeast Asia. Few baseline half-lives have been reported from Africa, where artemisinins were recently introduced.
We treated P. falciparum malaria in 215 Malian children aged 0.5-15 years with artesunate (0, 24, 48 hours) and amodiaquine (72, 96, 120 hours). We estimated half-life by measuring parasite density every 6 hours until undetectable and evaluated the effects of age, sex, ethnicity, and red blood cell (RBC) polymorphisms on half-life. We quantified the proportion of parasitized RBCs recognized by autologous immunoglobulin G (IgG).
The geometric mean half-life was 1.9 hours (95% confidence interval, 1.8-2.0) and did not correlate with parasite ex vivo susceptibility to artemisinins. In a linear model accounting for host factors, half-life decreased by 4.1 minutes for every 1-year increase in age. The proportion of parasitized RBCs recognized by IgG correlated inversely with half-life (r = -0.475; P = .0006).
Parasite clearance in response to artesunate is faster in Mali than in southeast Asia. IgG responses to parasitized RBCs shorten half-life and may influence this parameter in areas where age is not an adequate surrogate of immunity and correlates of parasite-clearing immunity have not been identified.
NCT00669084.
青蒿素耐药性是指疟原虫对青蒿素的清除半衰期延长，已在东南亚的恶性疟患者中有所描述。在青蒿素最近引入的非洲，报道的基线半衰期较少。
我们用青蒿琥酯（0、24、48 小时）和阿莫地喹（72、96、120 小时）治疗了 215 名 0.5-15 岁的马里儿童恶性疟。我们通过每 6 小时测量一次寄生虫密度直到无法检测到的方法来估计半衰期，并评估年龄、性别、种族和红细胞（RBC）多态性对半衰期的影响。我们量化了被自身免疫球蛋白 G（IgG）识别的寄生 RBC 的比例。
几何平均半衰期为 1.9 小时（95%置信区间，1.8-2.0），与寄生虫对青蒿素的体外敏感性无关。在一个考虑宿主因素的线性模型中，年龄每增加 1 岁，半衰期就会减少 4.1 分钟。被 IgG 识别的寄生 RBC 的比例与半衰期呈负相关（r = -0.475；P =.0006）。
与东南亚相比，青蒿琥酯在马里的寄生虫清除速度更快。对寄生 RBC 的 IgG 反应缩短了半衰期，并且在年龄不是免疫的充分替代物的地区，以及尚未确定清除寄生虫免疫的相关因素的地区，可能会影响这一参数。
NCT00669084。
