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疟原虫对常用抗疟药物的体外敏感性:以马里疟疾流行村庄肯涅罗巴为例。

Ex-vivo Sensitivity of Plasmodium falciparum to Common Anti-malarial Drugs: The Case of Kéniéroba, a Malaria Endemic Village in Mali.

机构信息

Malaria Research and Training Center, Mali International Center for Excellence in Research (Mali-ICER), University of Sciences, Techniques and Technologies of Bamako (USTTB), BP 1805, Bamako, Mali.

Hospital of Point-G/University of Sciences, Techniques and Technologies of Bamako (USTTB), Bamako, Mali.

出版信息

Drugs R D. 2020 Sep;20(3):249-255. doi: 10.1007/s40268-020-00313-4.

Abstract

BACKGROUND

In 2006, the National Malaria Control Program in Mali recommended artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. Since the introduction of artemisinin-based combination therapy, few reports are available on the level of resistance of Plasmodium falciparum to the most common anti-malarial drugs in Mali.

METHODS

From 2016 to 2017, we assessed the ex-vivo drug sensitivity of P. falciparum isolates in Kéniéroba, a village located in a rural area of southern Mali. We collected P. falciparum isolates from malaria-infected children living in Kéniéroba. The isolates were tested for ex-vivo sensitivity to commonly used anti-malarial drugs, namely chloroquine, quinine, amodiaquine, mefloquine, lumefantrine, dihydroartermisinin, and piperaquine. We used the 50% inhibitory concentration determination method, which is based on the incorporation of SYBR Green into the parasite's genetic material.

RESULTS

Plasmodium falciparum isolates were found to have a reduced ex-vivo sensitivity to quinine (25.7%), chloroquine (12.2%), amodiaquine (2.7%), and mefloquine (1.3%). In contrast, the isolates were 100% sensitive to lumefantrine, dihydroartermisinin, and piperaquine. A statistically significant correlation was found between 50% inhibitory concentration values of quinine and amodiaquine (r = 0.80; p < 0.0001).

CONCLUSIONS

Plasmodium falciparum isolates were highly sensitive to dihydroartermisinin, lumefantrine, and piperaquine and less sensitive to amodiaquine (n = 2), mefloquine (n = 1), and quinine (n = 19). Therefore, our data support the previously reported increasing trend in chloroquine sensitivity in Mali.

摘要

背景

2006 年,马里国家疟疾控制规划推荐青蒿素为基础的联合疗法作为治疗无并发症疟疾的一线药物。自引入青蒿素为基础的联合疗法以来,马里最常见抗疟药物对恶性疟原虫的耐药水平鲜有报道。

方法

2016 年至 2017 年,我们评估了位于马里南部农村地区肯涅罗巴村的恶性疟原虫分离株的体外药物敏感性。我们从肯涅罗巴村感染疟疾的儿童中采集恶性疟原虫分离株。对分离株进行体外药敏试验,检测常用抗疟药物的敏感性,包括氯喹、奎宁、阿莫地喹、甲氟喹、青蒿琥酯、双氢青蒿素和哌喹。我们使用 50%抑制浓度测定法,该方法基于将 SYBR Green 掺入寄生虫的遗传物质中。

结果

恶性疟原虫分离株对奎宁(25.7%)、氯喹(12.2%)、阿莫地喹(2.7%)和甲氟喹(1.3%)的体外敏感性降低。相比之下,分离株对青蒿琥酯、双氢青蒿素和哌喹 100%敏感。奎宁和阿莫地喹的 50%抑制浓度值之间存在显著的相关性(r=0.80;p<0.0001)。

结论

恶性疟原虫分离株对双氢青蒿素、青蒿琥酯和哌喹高度敏感,对阿莫地喹(n=2)、甲氟喹(n=1)和奎宁(n=19)的敏感性较低。因此,我们的数据支持了之前报道的马里氯喹敏感性增加的趋势。

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