塞内加尔达喀尔地区分离的恶性疟原虫对 7 种标准抗疟药物的体外敏感性。
Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs.
机构信息
1Laboratoire d’étude de la chimiosensibilité du paludisme, Fédération deslaboratoires, Hôpital Principal de Dakar, Dakar, Sénégal.
出版信息
Malar J. 2011 Oct 20;10:310. doi: 10.1186/1475-2875-10-310.
BACKGROUND
As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT) (which includes artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar.
METHODS
The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH) ELISA for the following drugs: chloroquine (CQ), quinine (QN), mefloquine (MQ), monodesethylamodiaquine (MDAQ), lumefantrine (LMF), dihydroartemisinin (DHA) and doxycycline (DOX).
RESULTS
After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50), the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P < 0.0001), LMF and QN (r = 0.511; P < 0.0001), LMF and DHA (r = 0.428; P = 0.0001), LMF and MQ (r = 0.413; P = 0.0002), QN and DHA (r = 0.402; P = 0.0003) and QN and MQ (r = 0.421; P = 0.0001).
CONCLUSIONS
The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.
背景
由于氯喹和磺胺多辛-乙胺嘧啶广泛耐药，自 2006 年以来，青蒿素为基础的联合疗法（ACT）（包括青蒿琥酯-咯萘啶和青蒿琥酯-阿莫地喹）已被推荐为塞内加尔的一线抗疟方案。此后，关于疟原虫对抗疟药物的体外敏感性的报道很少。为了研究 ACT 的广泛使用是否影响寄生虫的敏感性，在达喀尔的军事医院评估了当地分离株的体外抗疟药物敏感性。
方法
采用乳酸脱氢酶（pLDH）ELISA 法成功测定了 93 株来自达喀尔的恶性疟原虫分离株对以下药物的体外敏感性：氯喹（CQ）、奎宁（QN）、甲氟喹（MQ）、单去乙基阿莫地喹（MDAQ）、青蒿琥酯（LMF）、双氢青蒿素（DHA）和强力霉素（DOX）。
结果
将分离株的 IC50 按 3D7 参考株的敏感性进行转化（分离株 IC50/3D7 IC50）后，体外耐药分离株的低敏感性的流行率为 MQ 为 50%、CQ 为 22%、DOX 为 12%、QN 和 MDAQ 均为 6%，而 LMF 和 DHA 为 1%。对 CQ 和 MDAQ（r = 0.569；P < 0.0001）、LMF 和 QN（r = 0.511；P < 0.0001）、LMF 和 DHA（r = 0.428；P = 0.0001）、LMF 和 MQ（r = 0.413；P = 0.0002）、QN 和 DHA（r = 0.402；P = 0.0003）和 QN 和 MQ（r = 0.421；P = 0.0001）的反应之间显示出最强的显著正相关。
结论
2002 年 ACT 的引入并没有降低 DHA、MDAQ 和 LMF 等常见 ACT 成分对疟原虫的敏感性。然而，对 MQ 和 DOX 的耐药性降低的恶性疟原虫分离株的流行率有所增加。综上所述，这些数据表明，需要对塞内加尔疟原虫对抗疟药物的体外敏感性进行强化监测。
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