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[氯喹和磺胺多辛-乙胺嘧啶在阿比让北部(科特迪瓦)疗效的局限性:体内和体外联合研究]

[Limits of the efficacy of chloroquine and sulfadoxine-pyrimethamine in Northern Abidjan (Cote d'Ivoire): Combined in vivo and in vitro studies].

作者信息

Djaman Joseph, Abouanou Stéphane, Basco Leonardo, Koné Moussa

机构信息

Unité de parasitologie, Laboratoire de microbiologie de l'Institut national de santé publique (Abidjan), BP V 47 Abidjan Laboratoire de pharmacodynamie-biochimique, UFR Biosciences, Université de Cocody, Abidjan, Côte d'Ivoire.

出版信息

Sante. 2004 Oct-Dec;14(4):205-9.

Abstract

Antimalarial drug resistance in endemic malaria zones is first detected in vitro; when it reaches a certain threshold, it becomes perceptible and is expressed in therapeutic failure among subjects only slightly or not at all immune. This work conducted in northern Abidjan (Cote d'Ivoire) studied children with uncomplicated malaria, who were followed for 14 days (during the year 2000) in accordance with the WHO protocol for surveillance of antimalarial drug resistance. Concomitantly, the Plasmodium falciparum isolates were cultured in the presence of variable concentrations of chloroquine, pyrimethamine and quinine during in vitro chemosensitivity tests. The RPMI 1640 used as medium for the pyrimethamine did not contain PABA (para-amino benzoic acid) or folic acid. In all, 114 in vitro tests were completed, 33 to chloroquine, 32 to pyrimethamine, and 49 to quinine. Therapeutic efficacy was tested in 65 patients: 33 to chloroquine and 32 to sulfadoxine-pyrimethamine (SP). The results found 36% of the isolates were chloroquine-resistant (CQ-R) and 33% of the patients treated with chloroquine did not respond adequately (therapeutic failure, TF). The 12 CQ-R isolates corresponded to 11 TF subjects and 1 patient with adequate clinical and parasitological response. The concordance between the two tests was good (kappa=0.93). For pyrimethamine, 37.5% of the isolates were resistant (PYR-R), and 37.5% of patients responded adequately to SP. The 12 PYR-R isolates were from 12 TF subjects, so that kappa=1.0, when pyrimethamine resistance is defined as IC50 > 2,000 nM. Because of the elevated rate of chloroquine resistance, the national antimalaria program has recommended since July 2003 that amodiaquine be used as a first-line drug, to replace chloroquine. The relatively elevated number of TF with SP are a source of concern, because it is used in Yopougon (Abidjan). Additional studies to assess the prevalence of resistance to this combination in other areas of Abidjan city (Cote d' Ivoire) would be useful.

摘要

疟疾流行区的抗疟药耐药性首先在体外被检测到;当它达到一定阈值时,就会变得明显,并在免疫力较弱或根本没有免疫力的人群的治疗失败中表现出来。这项在阿比让北部(科特迪瓦)开展的研究,按照世界卫生组织抗疟药耐药性监测方案,对患有单纯性疟疾的儿童进行了为期14天(2000年期间)的跟踪。同时,在体外化学敏感性试验中,将恶性疟原虫分离株在不同浓度的氯喹、乙胺嘧啶和奎宁存在的情况下进行培养。用作乙胺嘧啶培养基的RPMI 1640不含对氨基苯甲酸(PABA)或叶酸。总共完成了114次体外试验,其中33次针对氯喹,32次针对乙胺嘧啶,49次针对奎宁。在65名患者中测试了治疗效果:33名使用氯喹,32名使用磺胺多辛-乙胺嘧啶(SP)。结果发现36%的分离株对氯喹耐药(CQ-R),33%接受氯喹治疗的患者反应不佳(治疗失败,TF)。12株CQ-R分离株对应11名治疗失败患者和1名临床及寄生虫学反应良好的患者。两项试验之间的一致性良好(kappa=0.93)。对于乙胺嘧啶,37.5%的分离株耐药(PYR-R),37.5%的患者对SP反应良好。12株PYR-R分离株来自12名治疗失败患者,因此当将乙胺嘧啶耐药性定义为IC50>2000 nM时,kappa=1.0。由于氯喹耐药率升高,自2003年7月起,国家抗疟规划建议使用阿莫地喹作为一线药物,以取代氯喹。使用SP治疗失败的人数相对较多令人担忧,因为它在约普贡(阿比让)使用。在阿比让市(科特迪瓦)其他地区评估这种联合用药耐药性流行情况的更多研究将很有用。

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