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泰国耐多药恶性疟原虫感染中抗疟药预处理的发生率及体外药物敏感性

Incidence of antimalarial pretreatment and drug sensitivity in vitro in multidrug-resistant Plasmodium falciparum infection in Thailand.

作者信息

Congpuong K, Sirtichaisinthop J, Tippawangkosol P, Suprakrob K, Na-Bangchang K, Tan-ariya P, Karbwang J

机构信息

Department of Communicable Diseases Control, Ministry of Public Health, Bangkok, Thailand.

出版信息

Trans R Soc Trop Med Hyg. 1998 Jan-Feb;92(1):84-6. doi: 10.1016/s0035-9203(98)90967-1.

DOI:10.1016/s0035-9203(98)90967-1
PMID:9692163
Abstract

Blood samples for determination of baseline antimalarial levels and sensitivity testing in vitro were collected from 411 patients with uncomplicated multidrug-resistant Plasmodium falciparum malaria (365 males, 46 females) before starting antimalarial treatment (62 in hospital and 349 as out-patients). Three hundred and eighty-two were successfully tested, and 110 (28.8%) and 20 (5.2%) patients, respectively, had detectable baseline blood mefloquine and quinine levels. Thirty-nine (10.2%), 44 (11.5%), 23 (6.0%) and 4 (1.1%) cases, respectively, had mefloquine concentrations in whole blood of < 100, 100-500, > 500-1000 and > 1000 ng/mL; the corresponding values for baseline plasma quinine levels were 0 (0%), 9 (2.4%), 3 (0.8%) and 9 (2.4%). None had detectable baseline artemether or artesunate. Sensitivity tests in vitro of pretreatment P. falciparum isolates showed the median IC50, IC90 and IC99 values (ranges in parentheses) for mefloquine, quinine and artemisinin to be 0.121 (0.046-0.715), 0.333 (0.085-3.0) and 0.64 (0.16-1.28) microM, 0.256 (0.064-1.315), 1.10 (0.154-20.49) and 2.56 (0.64-5.12) microM, and 0.02 (0.003-0.382), 0.112 (0.015-4.3) and 0.3 (0.03-3.0) microM, respectively. There was no difference in the sensitivity of P. falciparum isolates to these antimalarial compounds, regardless of the areas where patients had contracted the infection. Previous treatment with mefloquine or quinine was not statistically associated with a high incidence of resistance to these compounds.

摘要

在开始抗疟治疗前,从411例非复杂性耐多药恶性疟原虫疟疾患者(365例男性,46例女性)中采集血样,用于测定基线抗疟水平和体外敏感性试验(62例住院患者,349例门诊患者)。382例成功进行了检测,分别有110例(28.8%)和20例(5.2%)患者的基线血液中可检测到甲氟喹和奎宁水平。全血中甲氟喹浓度分别为<100、100 - 500、>500 - 1000和>1000 ng/mL的病例分别有39例(10.2%)、44例(11.5%)、23例(6.0%)和4例(1.1%);基线血浆奎宁水平的相应值分别为0(0%)、9例(2.4%)、3例(0.8%)和9例(2.4%)。无一例患者的基线蒿甲醚或青蒿琥酯可检测到。治疗前恶性疟原虫分离株的体外敏感性试验显示,甲氟喹、奎宁和青蒿素的IC50、IC90和IC99值中位数(括号内为范围)分别为0.121(0.046 - 0.715)、0.333(0.085 - 3.0)和0.64(0.16 - 1.28)μM,0.256(0.064 - 1.315)、1.10(0.154 - 20.49)和2.56(0.64 - 5.12)μM,以及0.02(0.003 - 0.382)、0.112(0.015 - 4.3)和0.3(0.03 - 3.0)μM。无论患者感染疟原虫的地区如何,恶性疟原虫分离株对这些抗疟化合物的敏感性均无差异。既往使用甲氟喹或奎宁治疗与对这些化合物的高耐药发生率无统计学关联。

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引用本文的文献

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Malar J. 2010 Feb 4;9:43. doi: 10.1186/1475-2875-9-43.
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Malar J. 2002 Oct 14;1:12. doi: 10.1186/1475-2875-1-12.
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Absence of significant pharmacokinetic and pharmacodynamic interactions between artemether and quinoline antimalarials.
蒿甲醚与喹啉类抗疟药之间不存在显著的药代动力学和药效学相互作用。
Eur J Drug Metab Pharmacokinet. 2000 Jul-Dec;25(3-4):171-8. doi: 10.1007/BF03192310.