Chloroquine resistance before and after its withdrawal in Kenya.
Chloroquine resistance before and after its withdrawal in Kenya.
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DOI：
10.1186/1475-2875-8-106
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发表时间：
2009-05-18
期刊：
影响因子：
3
通讯作者：
Nzila A
中科院分区：
文献类型：
--
作者：
Mwai L;Ochong E;Abdirahman A;Kiara SM;Ward S;Kokwaro G;Sasi P;Marsh K;Borrmann S;Mackinnon M;Nzila A
20世纪90年代，对氯喹耐药性的蔓延导致撒哈拉以南非洲大多数国家停止使用氯喹。在马拉维，在停药之后，耐药频率迅速降低，现在认为该药在停药仅仅九年之后再次有效。在本报告中，研究了1993年（CQ退出前）至2006年（CQ退出7年后）肯尼亚沿海地区（Kilifi）恶性疟原虫分离物对CQ耐药相关标记物的多态性。还比较了对替代药物乙胺嘧啶/磺胺嘧啶产生耐药性的二氢叶酸还原酶基因（dhfr）发生的变化。采用pcr -限制性内切酶法分析了与CQ抗性相关的突变，pfcrt密码子76、pfmdr1密码子86和dhfr密码子51、59和164。pfcrt-76、pfmdr1-86和dhfr基因分型分别为406株、240株和323株。从1993年到2006年，pfcrt-76突变体的频率从95%左右显著下降到60%左右，而pfmdr1-86突变体的频率没有下降，仍保持在75%左右。虽然在研究开始时dhfr突变的频率已经很高（约80%），但在研究期间这一频率增加到95%以上。对2006份样本进行了dhfr密码子164突变分析，均未发现该突变。与马拉维的研究一致，发现1999年正式停用CQ后，对CQ的耐药性下降，但与马拉维不同，基利菲对CQ的耐药性下降要慢得多。据估计，按照目前的下降速度，还需要13年的时间才能在基利菲恢复CQ的临床疗效。此外，在该药正式下架之前，CQ的耐药性正在下降，这表明在官方禁止之前，CQ的使用已经减少，可能是由于其临床疗效较差。
The spread of resistance to chloroquine (CQ) led to its withdrawal from use in most countries in sub-Saharan Africa in the 1990s. In Malawi, this withdrawal was followed by a rapid reduction in the frequency of resistance to the point where the drug is now considered to be effective once again, just nine years after its withdrawal. In this report, the polymorphisms of markers associated with CQ-resistance against Plasmodium falciparum isolates from coastal Kenya (Kilifi) were investigated, from 1993, prior to the withdrawal of CQ, to 2006, seven years after its withdrawal. Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared. Mutations associated with CQ resistance, at codons 76 of pfcrt, at 86 of pfmdr1, and at codons 51, 59 and 164 of dhfr were analysed using PCR-restriction enzyme methods. In total, 406, 240 and 323 isolates were genotyped for pfcrt-76, pfmdr1-86 and dhfr, respectively. From 1993 to 2006, the frequency of the pfcrt-76 mutant significantly decreased from around 95% to 60%, while the frequency of pfmdr1-86 did not decline, remaining around 75%. Though the frequency of dhfr mutants was already high (around 80%) at the start of the study, this frequency increased to above 95% during the study period. Mutation at codon 164 of dhfr was analysed in 2006 samples, and none of them had this mutation. In accord with the study in Malawi, a reduction in resistance to CQ following official withdrawal in 1999 was found, but unlike Malawi, the decline of resistance to CQ in Kilifi was much slower. It is estimated that, at current rates of decline, it will take 13 more years for the clinical efficacy of CQ to be restored in Kilifi. In addition, CQ resistance was declining before the drug's official withdrawal, suggesting that, prior to the official ban, the use of CQ had decreased, probably due to its poor clinical effectiveness.
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影响因子：
3
作者：
Briolant S;Parola P;Fusaï T;Madamet-Torrentino M;Baret E;Mosnier J;Delmont JP;Parzy D;Minodier P;Rogier C;Pradines B
通讯作者：
Pradines B
DOI：
10.1098/rstb.1999.0425
发表时间：
1999-04-29
影响因子：
6.3
作者：
Austin, DJ;Anderson, RM
通讯作者：
Anderson, RM
影响因子：
6.4
作者：
Cortese, JF;Caraballo, A;Plowe, CV
通讯作者：
Plowe, CV
影响因子：
64.8
作者：
FOOTE, SJ;KYLE, DE;COWMAN, AF
通讯作者：
COWMAN, AF
影响因子：
6.4
作者：
Lynch, Caroline;Pearce, Richard;Roper, Cally
通讯作者：
Roper, Cally