Suwandittakul Nantana, Chaijaroenkul Wanna, Harnyuttanakorn Pongchai, Mungthin Mathirut, Na Bangchang Kesara
Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani, Thailand.
Korean J Parasitol. 2009 Jun;47(2):139-44. doi: 10.3347/kjp.2009.47.2.139. Epub 2009 May 27.
The aim of the present study was to investigate antimalarial drug pressure resulting from the clinical use of different antimalarials in Thailand. The phenotypic diversity of the susceptibility profiles of antimalarials, i.e., chloroquine (CQ), quinine (QN), mefloquine (MQ), and artesunate (ARS) in Plasmodium falciparum isolates collected during the period from 1988 to 2003 were studied. P. falciparum isolates from infected patients were collected from the Thai-Cambodian border area at different time periods (1988-1989, 1991-1992, and 2003), during which 3 different patterns of drug use had been implemented: MQ + sulphadoxine (S) + pyrimethamine (P), MQ alone and MQ + ARS, respectively. The in vitro drug susceptibilities were investigated using a method based on the incorporation of [(3)H] hypoxanthine. A total of 50 isolates were tested for susceptibilities to CQ, QN, MQ, and ARS. Of these isolates, 19, 16, and 15 were adapted during the periods 1988-1989, 1991-1993, and 2003, respectively. P. falciparum isolates collected during the 3 periods were resistant to CQ. Sensitivities to MQ declined from 1988 to 2003. In contrast, the parasite was sensitive to QN, and similar sensitivity profile patterns were observed during the 3 time periods. There was a significantly positive but weak correlation between the IC(50) values of CQ and QN, as well as between the IC(50) values of QN and MQ. Drug pressure has impact on sensitivity of P. falciparum to MQ. A combination therapy of MQ and ARS is being applied to reduce the parasite resistance, and also increasing the efficacy of the drug.
本研究的目的是调查泰国临床使用不同抗疟药物所产生的抗疟药压力。研究了1988年至2003年期间收集的恶性疟原虫分离株中抗疟药(即氯喹(CQ)、奎宁(QN)、甲氟喹(MQ)和青蒿琥酯(ARS))敏感性谱的表型多样性。在不同时间段(1988 - 1989年、1991 - 1992年和2003年)从泰国 - 柬埔寨边境地区收集感染患者的恶性疟原虫分离株,在此期间分别实施了3种不同的用药模式:MQ + 磺胺多辛(S)+ 乙胺嘧啶(P)、单独使用MQ以及MQ + ARS。使用基于掺入[(3)H]次黄嘌呤的方法研究体外药物敏感性。总共测试了50株分离株对CQ、QN、MQ和ARS的敏感性。在这些分离株中,分别有19株、16株和15株是在1988 - 1989年、1991 - 1993年和2003年期间获得的。在这3个时间段收集的恶性疟原虫分离株对CQ耐药。从1988年到2003年,对MQ的敏感性下降。相反,该寄生虫对QN敏感,并且在这3个时间段观察到相似的敏感性谱模式。CQ和QN的半数抑制浓度(IC50)值之间以及QN和MQ的IC50值之间存在显著的正相关,但相关性较弱。药物压力对恶性疟原虫对MQ的敏感性有影响。正在应用MQ和ARS的联合疗法来降低寄生虫耐药性,并提高药物疗效。