Baird J K, Leksana B, Masbar S, Fryauff D J, Sutanihardja M A, Wignall F S, Hoffman S L
U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia.
Am J Trop Med Hyg. 1997 Jun;56(6):621-6. doi: 10.4269/ajtmh.1997.56.621.
To develop criteria for the diagnosis of resistance to chloroquine using an in vivo test, we examined published records of early clinical trials of quinine and chloroquine against Plasmodium vivax. These data established the timing of relapse by tropical P. vivax relative to therapy by these drugs. The first relapse occurred 17 days after initiating and three days after terminating quinine therapy. The median day of relapse was day 23, and 59% of the patients had relapsed by day 30 (n = 333). In contrast, no relapse occurred until day 36 following chloroquine treatment (n = 256). Data from our laboratory may help explain this difference; among 91 Indonesian patients with malaria, the mean whole blood levels of chloroquine (CQ) and desethylchloroquine (DCQ) were 141 ng/ml (95% confidence interval = 115-167) on day 28 after initiating standard therapy (25 mg base/kg in three doses over a 48-hr period). This exceeds the estimated minimal effective concentration of chloroquine (100 ng/ml of whole blood). Thus, chloroquine lingering in the blood for at least 28 days after starting standard therapy was sufficient to eliminate or at least suppress chloroquine-sensitive tropical P. vivax. We conclude that a parasitemia by P. vivax recurring in the 28 days after full compliance to standard chloroquine therapy demonstrates resistance. If the recurrence appears before day 16, it is almost certainly a recrudescence and between days 17 and 28 it may be either a recrudescence or a relapse by chloroquine-resistant parasites. Recurrences beyond day 28 could be relapse by chloroquine-sensitive P. vivax.
为了制定使用体内试验诊断氯喹耐药性的标准，我们查阅了奎宁和氯喹针对间日疟原虫的早期临床试验的已发表记录。这些数据确定了热带地区间日疟原虫复发相对于这些药物治疗的时间。首次复发发生在开始奎宁治疗后的17天以及终止奎宁治疗后的3天。复发的中位天数为第23天，59%的患者在第30天前复发（n = 333）。相比之下，氯喹治疗后直到第36天才出现复发（n = 256）。我们实验室的数据可能有助于解释这种差异；在91名印度尼西亚疟疾患者中，开始标准治疗（25毫克碱基/千克，分三次在48小时内给药）后第28天，氯喹（CQ）和去乙基氯喹（DCQ）的全血平均水平为141纳克/毫升（95%置信区间 = 115 - 167）。这超过了氯喹估计的最低有效浓度（全血100纳克/毫升）。因此，在开始标准治疗后氯喹在血液中持续至少28天足以消除或至少抑制对氯喹敏感的热带地区间日疟原虫。我们得出结论，在完全遵循标准氯喹治疗后28天内出现的间日疟原虫血症表明存在耐药性。如果复发出现在第16天之前，几乎肯定是再燃，而在第17天至28天之间，可能是再燃，也可能是对氯喹耐药的寄生虫引起的复发。超过第28天的复发可能是对氯喹敏感的间日疟原虫的复发。
