Karbwang J, Molunto P, Bunnag D, Harinasuta T
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Southeast Asian J Trop Med Public Health. 1991 Mar;22(1):72-6.
Quinine has been an effective drug for severe chloroquine-resistant falciparum malaria. However, there has been a decline in the sensitivity of Plasmodium falciparum to quinine. In 1978-1979 the cure rate was 94% compared to 86% in 1979-1980 and 76% in 1980-1981. The combination of quinine and tetracycline has improved the cure rate to 95-100%. However, the mechanism responsible for this has not been identified. We have compared plasma quinine levels on day 2, day 5 and day 7 (before and at 2 hours after dosing) in twenty-one patients with acute falciparum malaria who were treated with quinine alone (8 patients) or quinine in combination with tetracycline (8 patients) or quinine with tetracycline and primaquine (5 patients). All patients who received combination of quinine and tetracycline with or without primaquine responded well to the treatment with no recrudescence. Two patients who were treated with quinine alone had RI responses. Plasma quinine concentrations from the quinine alone group were significantly lower than those obtained from combination groups on days 2, 5 and 7. The minimal plasma quinine levels from quinine alone group were all lower than MIC, ie below 10 micrograms/ml while those obtained from the combination group were higher than MIC for 7 days. The results from the present study suggest that tetracycline has influence on the maintenance of plasma quinine levels above MIC throughout the treatment period. Therefore, this must be one possible explanation for the better cure rate.
奎宁一直是治疗严重氯喹耐药恶性疟的有效药物。然而,恶性疟原虫对奎宁的敏感性有所下降。1978 - 1979年治愈率为94%,而1979 - 1980年为86%,1980 - 1981年为76%。奎宁与四环素联合使用使治愈率提高到了95% - 100%。然而,其作用机制尚未明确。我们比较了21例急性恶性疟患者在第2天、第5天和第7天(给药前及给药后2小时)的血浆奎宁水平,这些患者分别接受单独奎宁治疗(8例)、奎宁与四环素联合治疗(8例)或奎宁与四环素及伯氨喹联合治疗(5例)。所有接受奎宁与四环素联合治疗(无论是否加用伯氨喹)的患者对治疗反应良好,无复发。2例单独接受奎宁治疗的患者有复发反应。单独使用奎宁组在第2天、第5天和第7天的血浆奎宁浓度显著低于联合治疗组。单独使用奎宁组的最低血浆奎宁水平均低于最低抑菌浓度,即低于10微克/毫升,而联合治疗组的最低血浆奎宁水平在7天内均高于最低抑菌浓度。本研究结果表明,四环素在整个治疗期间对维持血浆奎宁水平高于最低抑菌浓度有影响。因此,这必定是治愈率更高的一种可能解释。