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在磺胺多辛-乙胺嘧啶被采用作为一线治疗之前,坦桑尼亚农村地区恶性疟原虫的耐药模式及二氢叶酸还原酶/二氢蝶酸合酶基因型

Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.

作者信息

Eriksen J, Mwankusye S, Mduma S, Kitua A, Swedberg G, Tomson G, Gustafsson L L, Warsame M

机构信息

Division of Clinical Pharmacology, Karolinska Institute at Karolinska University Hospital, Stockholm, Sweden.

出版信息

Trans R Soc Trop Med Hyg. 2004 Jun;98(6):347-53. doi: 10.1016/j.trstmh.2003.10.010.

Abstract

A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine.

摘要

在坦桑尼亚将磺胺多辛-乙胺嘧啶(SP)作为单纯性疟疾的一线治疗药物之前,开展了一项研究,以评估恶性疟原虫的耐药模式以及二氢叶酸还原酶/二氢蝶酸合酶(DHFR/DHPS)基因型的出现情况。117名患有临床单纯性疟疾的五岁以下儿童被随机分配接受氯喹(CQ)(25毫克/千克)或SP(25毫克磺胺多辛和1.25毫克乙胺嘧啶/千克)的标准治疗。对患者进行了28天的监测。SP组和CQ组分别有98%(n = 58)和90%(n = 59)的患者实现了临床康复。在寄生虫学方面,SP组14%的患者和CQ组51%的患者表现出RII/RIII耐药性。当将治疗前的血药水平与治疗结果以及寄生虫耐药程度与突变数量相关联时,未发现相关性。两组患者从第0天到第28天血红蛋白水平总体均有显著升高。磺胺多辛-乙胺嘧啶产生了可接受的临床反应,但在该药物作为一线治疗药物引入前两年就观察到的高度寄生虫耐药性(RII/RIII)令人担忧,尤其是考虑到磺胺多辛和乙胺嘧啶的长半衰期。

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