Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon:: implications for the validity of tests in vitro vs. in vivo
Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon:: implications for the validity of tests in vitro vs. in vivo
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DOI：
10.1016/s0035-9203(02)90345-7
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发表时间：
2002-11-01
影响因子：
2.2
通讯作者：
Kremsner, PG
中科院分区：
文献类型：
--
作者：
Borrmann, S;Binder, RK;Kremsner, PG
恶性疟原虫对抗疟药物的抗药性日益增强，是生活在热带非洲疟疾流行地区的人们面临的一个主要风险因素。在加蓬的兰巴内，自1992年以来一直使用世卫组织标准微量试验定期监测体外恶性疟原虫对氯喹的敏感性。结果表明，从1994年起，体外氯喹抗性显着下降，到2000年，约70%的寄生虫分离株似乎是敏感的体外氯喹。2001年，我们进行了一项临床研究，重新评估氯喹在体内治疗无并发症恶性疟原虫疟疾的疗效。本研究纳入了26例4 - 15岁的患者。最出乎意料的是，该研究证明了体内对氯喹的高度耐药性（第28天的失败率为100%）。因此，使用相同的方案重复体外寄生虫对氯喹的敏感性试验，不同之处在于将先前使用的市售预给药WHO培养平板替换为独立给药平板。所有检测的恶性疟原虫分离株均对氯喹高度耐药，与我们的临床结果相关性良好。我们的结论是，恶性疟原虫氯喹的高水平的耐药性持续在研究区域。对基本试验材料进行质量控制的疏忽或缺失可能导致无效的研究结果和错误的结论，在抗疟药物体外敏感性模式出现重大波动的情况下，应始终予以怀疑。此外，我们的研究结果突出了体内试验在提供抗疟药在特定区域的疗效的可靠估计方面的最高价值。
Increasing resistance of Plasmodium falciparum to antimalarial drugs presents a major risk factor for people living in endemic areas of tropical Africa. In Lambarene, Gabon, regular surveillance of chloroquine sensitivity of P. falciparum in vitro has been carried out since 1992 using the WHO standard microtest. Results indicated that from 1994 onwards chloroquine resistance in vitro decreased significantly and that by 2000, about 70% of parasite isolates seemed to be sensitive to chloroquine in vitro. In 2001, we conducted a clinical study to reassess the efficacy of chloroquine in vivo for the treatment of uncomplicated P. falciparum malaria. Twenty-six patients aged 4-15 years were included in this study. Most unexpectedly, the study demonstrated high-grade resistance to chloroquine in vivo (failure rate on day 28 of 100%). As a consequence, tests of parasite susceptibility to chloroquine in vitro were repeated using the same protocol except for the replacement of previously used commercially available predosed WHO culture plates by independently dosed plates. All tested P. falciparum isolates were highly resistant to chloroquine, correlating well with our clinical findings. We concluded that high level resistance of P. falciparum to chloroquine persists in the study area. Neglect or absence of quality controls of essential test material can lead to invalid study results and wrong conclusions and should always be suspected in the case of major fluctuations in the sensitivity patterns of an antimalarial drug in vitro. In addition, our results highlight the supreme value of tests in vivo in providing reliable estimates of the efficacy of an antimalarial in a specific area.