AAC:改善疟疾的疗法新进展

2010-05-04 00:00 · Chad

法国和美国科学家日前表示,他们发现了恶性疟原虫对于青蒿素类药物的抗药机制,这一发现将有助于科学家研究疟疾的新疗法。 据法国国家科研中心介绍,每年全世界约有100万人死于疟疾,但医学界至今仍未研制出针对这种传染病的有效疫苗。作为疟原虫的一种,恶性疟原虫致病性极强,它主要存在于非洲、

法国和美国科学家日前表示,他们发现了恶性疟原虫对于青蒿素类药物的抗药机制,这一发现将有助于科学家研究疟疾的新疗法。

据法国国家科研中心介绍,每年全世界约有100万人死于疟疾,但医学界至今仍未研制出针对这种传染病的有效疫苗。作为疟原虫的一种,恶性疟原虫致病性极强,它主要存在于非洲、南美和亚洲的热带地区,并与80%的人类疟疾相关。十几年来,医学界一直使用青蒿素及其衍生产品对病人进行治疗,它不但治愈率高,而且见效很快。但在去年7月,科学家们发现少数恶性疟原虫对青蒿素类药物表现出抗药性,这为疟疾的防治工作敲响了警钟。

为此,该机构与法国健康与医疗研究所、美国国家健康研究所合作,对恶性疟原虫的抗药机制进行了研究。科学家发现,在青蒿素发挥药效的时候,恶性疟原虫就会进入“休眠状态”,等到药效一过,它又会重新“苏醒”过来,不过只有处于红细胞寄生周期第一阶段的恶性疟原虫才具有这种能力。

研究人员认为,这一发现将帮助科学家更好的了解疟原虫的抗药机制,从而改善疟疾的疗法。相关研究成果已公布在最新一期的美国《抗微生物制剂与化学疗法》月刊上。

疟疾是由疟原虫引起的疾病,多由蚊子传播,在热带及亚热带地区发病较多。疟疾症状包括发热、头痛、呕吐等,严重时可引起死亡。


推荐原文出处:

Antimicrobial Agents and Chemotherapy doi:10.1128/AAC.01636-09

Increased Tolerance to Artemisinin in Plasmodium falciparum Is Mediated by a Quiescence Mechanism

Benoit Witkowski,1,2, Joel Lelièvre,1,2,, María José López Barragán,3 Victor Laurent,1,2 Xin-zhuan Su,3 Antoine Berry,2,4, and Fran?oise Benoit-Vical1,2,*

CNRS, Laboratoire de Chimie de Coordination, UPR8241, Toulouse, France, and Université de Toulouse III, Toulouse, France,1 Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse, and Faculté de Médecine de Rangueil, Université de Toulouse III, Toulouse, France,2 Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,3 UMR3 MD-UM-UPS, Université Paul Sabatier Toulouse III, Toulouse, France4

Artemisinin (ART)-based combination therapies (ACTs) are the first-line drugs―and often the last treatments―that can effectively cure Plasmodium falciparum infections. Unfortunately, the decreased clinical efficacy of artesunate, one of the major ART derivatives, was recently reported along the Thailand-Cambodia border. Through long-term artemisinin pressure in vitro, we have obtained an ART-tolerant strain that can survive extremely high doses of ART. We showed that drug pressure could induce a subpopulation of ring stages into developmental arrest, which can explain the ART tolerance in P. falciparum. We also observed interesting transcriptomic modifications possibly associated with the acquisition of ART tolerance. These modifications include the overexpression of heat shock and erythrocyte surface proteins and the downexpression of a cell cycle regulator and a DNA biosynthesis protein. This study highlights a new phenomenon in the Plasmodium response to ART that may explain the delayed clearance of parasites after artesunate treatment observed on the Thailand-Cambodia border and that provides important information for achieving a better understanding of the mechanisms of antimalarial resistance.

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