Mwangi Victor Irungu, Mumo Ruth Mwende, Kiboi Daniel Muthui, Omar Sabah Ahmed, Ng'ang'a Zipporah Waithera, Ozwara Hastings Suba
Institute of Primate Research, Nairobi, Kenya.
J Infect Dev Ctries. 2016 Jun 30;10(6):635-42. doi: 10.3855/jidc.7556.
Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei.
Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined.
At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed.
Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine-resistant parasites.
化疗仍然是控制疟疾的最有效方法，疟疾是撒哈拉以南非洲的一个主要公共卫生问题。在非洲大规模使用蒿甲醚-本芴醇联合疗法治疗疟疾使本芴醇容易产生耐药性。有必要确定可作为本芴醇替代品用于联合疗法的药物。亚甲蓝是一种合成的抗高铁血红蛋白血症药物，已被证明具有抗疟特性，使其成为药物重新利用的候选药物。本研究旨在确定亚甲蓝对伯氏疟原虫耐本芴醇和耐乙胺嘧啶菌株的抗疟原虫作用。
使用经典的四天试验评估亚甲蓝对感染耐本芴醇和耐乙胺嘧啶伯氏疟原虫的小鼠体内的活性。45毫克/千克/天的剂量对测试ED90有效。测定了疟原虫血症和小鼠存活率。
在45毫克/千克/天的剂量下，亚甲蓝在治疗后至少6天内对耐本芴醇和耐乙胺嘧啶的伯氏疟原虫持续产生显著的寄生虫抑制作用，超过99%（分别为p = 0.0086和p = 0.0191）。未观察到严重不良反应。
我们的结果表明，浓度为45毫克/千克/天的亚甲蓝对耐本芴醇和耐乙胺嘧啶的伯氏疟原虫有超过99%的抑制作用，持续6天。这表明亚甲蓝在开发针对耐本芴醇和耐乙胺嘧啶寄生虫的抗疟药物方面具有潜在用途。
