Suwanarusk Rossarin, Russell Bruce, Ong Alice, Sriprawat Kanlaya, Chu Cindy S, PyaePhyo Aung, Malleret Benoit, Nosten François, Renia Laurent
Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, Singapore.
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
J Antimicrob Chemother. 2015 Jan;70(1):124-9. doi: 10.1093/jac/dku326. Epub 2014 Aug 21.
Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine.
To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser.
P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule.
Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria.
亚甲蓝曾因具有令人不安但较为轻微的副作用而被弃用，如今在现代医学药典中重新获得了一席之地。间日疟原虫和恶性疟原虫耐药性的持续传播也促使近期对亚甲蓝强大的抗疟特性进行了重新审视。在此，我们研究疟原虫分离株对亚甲蓝的体外敏感性概况；这些分离株来自泰国 - 缅甸边境地区，在该地区用氯喹治疗间日疟时治疗失败率不断上升。
为此，我们使用了一种新开发的体外敏感性检测方法，该方法利用流式细胞术以及一台配备近紫外激光的便携式流式细胞仪。
间日疟原虫（亚甲蓝半数抑制浓度（IC50）中位数为3.1纳摩尔，四分位间距为1.7 - 4.3纳摩尔）和恶性疟原虫（亚甲蓝IC50中位数为1.8纳摩尔，四分位间距为1.6 - 2.3纳摩尔）在生理相关水平下对亚甲蓝治疗敏感。遗憾的是，在亚甲蓝联合治疗中添加氯喹会显著降低该分子的体外有效性。
我们的数据支持进一步努力将亚甲蓝用作一种安全、低成本的抗疟药物来治疗耐药性疟疾。
