中缅边境地区磷酸哌喹和磷酸咯萘啶治疗恶性疟的效果观察  

The therapeutic efficacy of piperaquine and pyronaridine against Plasmodium falciparum in the China-Myanmar border region

作　　者：张苍林[1] 王剑 王微莉 邓艳[1] 吴静 周红宁[1] ZHANG Cang-lin;WANG Jian;WANG Wei-li;DENG Yan;WU Jing;ZHOU Hong-ning(Yunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research,Yunnan Provincial Center for Malaria Research,Yunnan Provincial Collaborative Innovation Center for Public Health and Disease Prevention and Control,(Training of)Innovative Teams in Key Techniques for Vector-borne Disease Control and Prevention,Expert Workstation of Professor Jiarig Lubing,Yiuuian Institute of Parasitic Diseases,Puer,Yunnan,China 665099;Yunnan Institute of Endemic Disease Control and Prevention,Dali,Yunnan,China 671000;Nujiang Center for Disease Control and Prevention,Nujiang,Yunnan,China 673200)

机构地区：[1]云南省虫媒传染病防控研究重点实验室,云南省疟疾研究中心,云南省寄生虫病防治所虫媒传染病防控关键技术省创新团队(培育),普洱市江陆斌专家工作站,云南省寄生虫病防治所,云南普洱665099 [2]云南省地方病防治所 [3]怒江州疾病预防控制中心

出　　处：《中国病原生物学杂志》2020年第9期1075-1079,共5页Journal of Pathogen Biology

基　　金：云南公共卫生与疾病防控协同创新中心项目(No.2014YNPHXT03);国家自然科学基金项目(No.81160357,30960327,30660160)。

摘　　要：目的了解中缅边境地区恶性疟原虫(Plasmodium falciparum)对磷酸哌喹和磷酸咯萘啶药物的敏感性,为当地制定恶性疟药物治疗对策提供依据。方法选取缅甸拉咱市镜检确诊为单一恶性疟原虫感染的现症患者作为观察对象,随机分为A、B两组,分别用磷酸哌喹(piperaquine)和磷酸咯萘啶(pyronaridine)治疗。参照WHO推荐方案,于服药第0、1、2、3、7、14、21和28 d检测原虫密度,并观察患者症状、体温和药物不良反应等。应用SPSS 23.0分析两组患者的治疗效果及用药安全性。结果共收治恶性疟病例66例,其中符合研究要求的病例40例。成功测定病例37例,占92.5%(37/40),平均年龄17.6(4~48)岁;7例出现轻度药物不良反应,占17.5%(7/40)。A组治愈率为72.2%(13/18),具有磷酸哌喹抗性的病例在临床治愈(ACPR)、晚期原虫治疗失败(LPF)、晚期临床失败(LCF)和早期治疗失败(ETF)中占比分别为22.2%、5.6%、16.7%和5.6%,其抗性程度主要是二级抗性(RⅡ),占88.9%;三级抗性(RⅢ)占11.1%;B组治愈率为68.4%(13/19),具有磷酸咯萘啶抗性的病例在临床疗效ACPR、LPF、LCF和ETF中占比分别为21.1%、5.3%、26.3%和0,抗性程度主要是二级抗性(RⅡ),占90.0%、一级抗性(RⅠ)占10.0%。A、B两组中出现LPF、LCF和ETF的病例均为药物抗性病例,除B组1例LPF病例的抗性为RⅠ外,其余病例的抗性均为RⅡ。Spearman秩相关系数检验分析显示,两种药物药效与临床疗效之间存在相关性(r=0.568,P<0.05)。结论磷酸哌喹和磷酸咯萘啶对中缅边境地区恶性疟治疗效果良好,建议缅甸边境地区相关部门应加强恶性疟原虫对抗疟药敏感性的监测。Objective To ascertain the sensitivity of piperaquine and pyronaridine in treating uncomplicated falciparum malaria in the China-Myanmar border region and to assess the efficacy of these antimalarial drugs and guide the use of antimalarials in the area.Methods A clinical trial was conducted in the Town of Laiza,Myanmar in 2009.Subjects were patients infected with P.falciparum that were identified via a microscopic examination.Patients were randomly allocated into group A,which was treated with piperaquine,or group B,which was treated with pyronaridine.Patients were then followed-up on D0,D1,D2,D3,D7,D14,D21,and D28 to observe parasite density,symptoms,body temperature,and adverse drug reactions,drug resistance and efficacy in accordance with the 2003 WHO guidelines.The relationship between drug resistance and efficacy against isolates was calculated in SPSS 23.0 using Spearman’s rank correlation coefficient test.Results A total of 66 patients with a P.falciparum infection were identified via a microscopic examination.Forty patients satisfying the criteria for an in vivo test were randomly allocated into group A and B on average.In total,37 patients(92.5%,37/40)were successfully identified with an in vivo test,with an average age of 17.6 years(range:4-48 years).No serious adverse drug reactions were noted.Mild adverse reactions were noted in 7 patients(17.5%,7/40).An adequate clinical and parasitological response(ACPR)was achieved at a rate of 72.2%(13/18)in group A and 68.4%(13/19)in group.In group A,there were more patients with an RⅡresponse(88.9%)than with an RⅢresponse(11.1%).An ACPR was achieved in 22.2%of piperaquine-resistant patients in group A,late parasitological failure(LPF)occurred in 5.6%,late clinical failure(LCF)occurred in 16.7%,and early treatment failure(ETF)occurred 5.6%.In group B,there were far more patients with an RⅡresponse(90.0%)than patients with an RⅠresponse(10.0%).An ACPR was achieved in 21.1%of pyronaridine-resistant patients in group B,LPF occurred in 5.3%,LCF occurred in

关 键 词：疟原虫 恶性 敏感性 体内检测 磷酸哌喹 磷酸咯萘啶 拉咱市 缅甸 

分 类 号：R531.3[医药卫生—内科学]