蒿甲醚对曼氏血吸虫的作用:剂量与效应的关系和虫的形态学和组织病理学的变化

目的　应用感染曼氏血吸虫 (利比里亚株 )的小鼠观察蒿甲醚单剂量与效应的关系,虫体肝移及蒿甲醚所引起的虫的形态学和组织病理学变化。　方法　感染21d童虫的小鼠一次口服蒿甲醚12.5mg/kg至600mg/kg不同剂量 ,治后28d剖检观察各组虫数。感染46d或70d成虫的小鼠一次口服蒿甲醚40 0mg/kg后8～14d ,观察虫体肝移及其形态和组织病理学变化。　结果　蒿甲醚对21d童虫的最低有效剂量为200mg/kg ,减虫率为 81%。用蒿甲醚治疗后8h成虫开始肝移,3～7d全部肝移,14d有31%的虫返回肠系膜静脉。成虫虫体萎缩,咽部扩大,肠管膨胀及其色素减少。雌虫局部体表受损,白细胞附着,卵巢及卵黄腺变性退化,以及雄虫睾丸萎缩等。在肝内的虫体被嗜酸粒细胞为主的炎细胞包围和浸润。　结论　蒿甲醚对小鼠曼氏血吸虫21d童虫的最低有效剂量为200mg/kg ,可引起曼氏血吸虫成虫萎缩、退化或死亡。在肝内受损的虫体主要是被嗜酸粒细胞包围和侵袭所致。     

感染日本血吸虫小鼠用双氢青蒿素连续给药及与吡喹酮伍用的疗效观察

目的观察双氢青蒿素连续多次给药及与吡喹酮伍用对日本血吸虫童虫和成虫的杀灭效果。方法采用腹部贴片感染小鼠,每鼠感染日本血吸虫尾蚴(40±1)条后随机分组。分别在感染后第6天或第34天,用双氢青蒿素200、300、400mg/kg或600mg/kg灌服治疗,日1次,连服3d。在小鼠感染后第7天或第35天,分别灌服双氢青蒿素或吡喹酮各300mg/kg以及2种药物剂量同时灌服,或双氢青蒿素于小鼠感染后第7天或第35天灌服,而吡喹酮则在感染后第6天或第8天,以及第34天或第36天给药。2次试验各设有1组不治疗的对照。治疗组和对照组小鼠均于感染后50d解剖,收集成虫,计算减虫率和减雌率。结果在感染后第6天,连续3次灌服剂量分别为200、300、400mg/kg和600mg/kg双氢青蒿素,小鼠减虫率分别为69.16%、80.68%、87.11%和90.62%,减雌率分别为62.19%、75.61%、83.65%和92.16%。在感染后第34天,连续3次灌服给药组小鼠减虫率分别为73.90%、74.99%、84.19%和85.49%,减雌率分别为83.84%、92.91%、94.05%和95.27%。在童虫期(感染后7d),单剂量双氢青蒿素(300mg/kg)与吡喹酮(300mg/kg)联合给药组小鼠减虫率为19.66%;单剂量双氢青蒿素(300mg/kg)第7天服用,吡喹酮第6天或第8天给药组小鼠减虫率分别为42.96%和57.46%。在成虫期(感染后35d),双氢青蒿素(300mg/kg)与吡喹酮(300mg/kg)联合给药组小鼠减虫率为70.21%,吡喹酮第34天或第36天给药组小鼠减虫率分别为60.82%和81.51%。结论双氢青蒿素在童虫期和成虫期连续给药可增强其抗日本血吸虫作用效果。在童虫期,双氢青蒿素与吡喹酮伍用或吡喹酮第6天用药可降低抗日本血吸虫作用效果;在成虫期,双氢青蒿素与吡喹酮伍用或吡喹酮第36天用药可增强抗日本血吸虫效果。     

3种青蒿素衍生物对日本血吸虫吡喹酮抗性株童虫的体内作用效果观察

目的观察3种青蒿素衍生物双氢青蒿素、青蒿琥酯和蒿甲醚对日本血吸虫吡喹酮抗性株童虫的体内作用效果。方法以经11轮亚治疗剂量吡喹酮筛选的日本血吸虫为吡喹酮抗性株,以未暴露于吡喹酮的日本血吸虫作为吡喹酮敏感株,收集2虫株尾蚴感染小鼠,以300mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚对感染后7~8 d童虫分别进行2次灌服用药(总剂量600 mg/kg),所有小鼠于感染后45 d解剖,收集小鼠体内成虫并计数,计算减虫率和减雌率。结果 300 mg/kg双氢青蒿素、蒿甲醚和青蒿琥酯2日疗法(总剂量600 mg/kg)对日本血吸虫吡喹酮敏感株7~8 d童虫的减虫率为69.8%~71.0%,减雌率为75.4%~79.8%;对日本血吸虫吡喹酮抗性株7~8 d童虫的减虫率为64.6%~66.1%,减雌率为69.3%~71.1%,差异均无统计学意义(均p0.05)。结论 日本血吸虫吡喹酮抗性株对青蒿素类衍生物双氢青蒿素、青蒿琥酯和蒿甲醚依然敏感,青蒿素衍生物与吡喹酮在日本血吸虫中不存在交叉抗药性。     

血吸虫对吡喹酮抗药性的研究ⅩⅢ日本血吸虫吡喹酮抗药性的实验诱导

目的实验研究在吡喹酮药物压力下中国大陆日本血吸虫对吡喹酮产生抗药性的可能性。方法取采自湖南省血吸虫病流行区湖滩现场和江苏省实验室传代的感染性钉螺实验室逸蚴,获得日本血吸虫尾蚴感染小鼠,从感染鼠肝脏分离成熟虫卵孵化毛蚴感染湖北钉螺,建立现场采集株和实验室传代株日本血吸虫小鼠钉螺实验室生活史循环。用定量尾蚴（40条/鼠）感染小鼠,感染35d后将小鼠随机分为对照组和抗性诱导组：对照组小鼠感染后45d解剖收集肠系膜静脉和肝门脉静活虫体,计算虫负荷（条/鼠）;抗性诱导组小鼠采用灌胃法一次口服亚治疗剂量吡喹酮进行治疗,服药22d后解剖收集肠系膜静脉和肝门脉静存活虫体。计算虫负荷（条/鼠）和减虫率,完成首轮诱导。取抗性诱导组小鼠肝脏,分离虫卵,实验室孵化出毛蚴重新感染钉螺,感染后的钉螺经25℃生化培养箱内饲养60~70d后,分离感染性钉螺并逸蚴,用成熟尾蚴感染小鼠,开始新一轮循环诱导。首轮诱导吡喹酮口服剂量为100mg/kg,后每循环2~3轮增加100mg/kg口服剂量。取完成8轮诱导后和未经诱导原代虫株的尾蚴感染小鼠,感染35d后分别采用300mg/kg和600mg/kg吡喹酮一次性灌胃治疗感染小鼠,服药后14d解剖感染鼠,收集活虫,计算各虫株减虫率,评价虫株经8轮诱导后对吡喹酮敏感性的变化。结果在实验室内建立了江苏实验室传代株和湖南现场采集株2个虫株,并对其实施了8轮诱导。江苏实验室传代株在小鼠体内经第1轮口服100mg/kg吡喹酮治疗后减虫率为22.3%,第8轮口服300mg/kg吡喹酮治疗后减虫率为53.7%,减虫率随口服吡喹酮剂量增加而增加;湖南现场采集株在小鼠体内经第1轮口服100mg/kg吡喹酮治疗后减虫率为66.8%,第8轮口服300mg/kg吡喹酮治疗后减虫率仅为20.6%,减虫率随口服吡喹酮剂量增加而显著降低。未经吡喹酮诱导的江苏实验室传代株在小鼠体内经300mg/kg和600mg/kg吡喹酮治疗后,减虫率分别为71.5%和97.4%;经8轮吡喹酮筛选治疗后该虫株减虫率降至32.6%和68.1%。未经吡喹酮诱导的湖南现场采集株在小鼠体内经300mg/kg和600mg/kg吡喹酮治疗后,减虫率分别为70.8%和97.5%;经8轮吡喹酮筛选治疗后该虫株减虫率降至45.7%和61.9%。结论中国大陆日本血吸虫在吡喹酮持续药物压力下可产生抗药性,但不同虫株间对吡喹酮敏感性存在差异,药物压力下产生抗性的潜能也存在差异。中国大陆日本血吸虫吡喹酮抗性株的建立,可为研究日本血吸虫吡喹酮抗性机制及其检测和监测技术奠定基础。     

Schistosoma japonicum and S. mansoni: ultrastructural damage in the tegument and reproductive organs after treatment with levo- and dextro-praziquantel

Ultrastructural observations were made of changes in the tegument and reproductive organs of Schistosoma japonicum and S. mansoni from ICR mice after treatment with praziquantel (PZQ), levo-PZQ, and dextro-PZQ at a single oral dose of 500 mg/kg body weight. No marked difference in types and extent of lesions of the tegument of S. japonicum was found between the compounds regardless of the time of worm recovery after treatment. This was equally true of S. mansoni. Degeneration of the testis, ovary, and vitelline gland of S. japonicum was more prominent in worms administered PZQ and levo-PZQ than in those receiving dextro-PZQ. In S. mansoni, extensive regression of the reproductive organs was observed in male and female worms treated with PZQ and dextro-PZQ, while no serious damage was seen in worms treated with levo-PZQ.     

蒿甲醚和青蒿琥酯对感染曼氏血吸虫小鼠治疗作用的初步研究

目的了解蒿甲醚和青蒿琥酯对小鼠曼氏血吸虫作用的效果.方法将小鼠随机分成12个实验组及1个对照组,以皮下注射的方法,每鼠接种约80条尾蚴,接种尾蚴46 d后,分别以蒿甲醚或青蒿琥酯灌胃治疗,第1天,分别以400、300、200 mg/kg的剂量1次灌胃;第2～7天,则每天分别按以上剂量的半量灌胃,7 d灌胃的总剂量分别为1 600、1 200、800 mg/kg.总量1剂组,在第7天,分别按1 600、1 200、800 mg/kg剂量1次灌胃.另设感染阳性对照组,不加治疗. 结果蒿甲醚7日疗法1 600、1 200、800 mg/kg剂量组减虫率分别为53.0%、49.0%和53.0%,减雌率为78.0%～82.0%,总量1剂组效果与7日疗法基本相同.青蒿琥酯7日疗法相应剂量减虫率分别为16.0%、37.0%和49.0%.结论蒿甲醚和青蒿琥酯对小鼠曼氏血吸虫具有一定的杀虫效果,蒿甲醚在疗效和毒性方面稍佳.     

双氢青蒿素抗日本血吸虫作用的体内实验观察

目的观察不同发育阶段日本血吸虫对双氢青蒿素的敏感性,探索双氢青蒿素抗日本血吸虫的效果。方法采用尾蚴腹部贴片法感染小鼠,每鼠感染日本血吸虫尾蚴40条;在血吸虫不同发育阶段灌服用药,于感染后50 d解剖小鼠,收集成虫,计算减虫率和减雌率。①在小鼠感染后2 h,3、5、7、10、14、18、21、28 d和35 d灌服双氢青蒿素（300 mg/kg）,观察双氢青蒿素对不同发育阶段血吸虫的作用效果。②以不同剂量双氢青蒿素分别给感染后7 d或35 d的小鼠用药,观察双氢青蒿素抗日本血吸虫作用的量-效关系。③以不同药物剂量分别在感染后第7天和第35天给药（共2次）,观察双氢青蒿素对日本血吸虫的作用效果。结果300 mg/kg双氢青蒿素一次灌服用药对7 d龄童虫和35 d龄成虫有明显杀灭作用,减虫率分别为64.81%和60.47%,减雌率分别为73.81%和90.48%。以200、300、400 mg/kg和600 mg/kg双氢青蒿素治疗感染后7 d小鼠,减虫率分别为46.84%、60.63%、59.55%和60.21%,减雌率分别为59.73%、72.29%、72.58%和76.61%;治疗感染后35 d小鼠,减虫率分别为47.23%、62.33%、76.31%和83.63%,减雌率分别为59.73%、89.36%、89.65%和93.96%;在感染后第7天和第35天共治疗2次,减虫率分别为58.16%、82.66%、83.42%和83.79%,减雌率分别为68.69%、90.43%、93.74%和94.63%。结论双氢青蒿素具有一定的抗日本血吸虫作用,对7 d童虫和35 d成虫较为敏感。     

血吸虫对吡喹酮抗药性的研究XⅧ日本血吸虫吡喹酮抗性株与敏感株混合感染子代成虫对吡喹酮的敏感性

目的　测定实验诱导产生的日本血吸虫吡喹酮抗性株与实验室保种传代的日本血吸虫吡喹酮敏感株混合感染后产生的子代成虫对吡喹酮的敏感性。方法　取实验室诱导产生的日本血吸虫吡喹酮抗性株[吡喹酮半数有效剂量（ED50值）为277.4 mg/kg]尾蚴与实验室传代保种的日本血吸虫吡喹酮敏感株（吡喹酮ED50值为99.6 mg/kg）尾蚴,分别按1∶1和2∶1混合后感染小鼠。后在实验室经小鼠⁃钉螺循环8代后,取尾蚴感染小鼠。感染35 d后将小鼠分为对照组及5个给药组。5个给药组分别按37.5、75、150、300 mg/kg和600 mg/kg剂量一次性灌胃给予吡喹酮,对照组给予2.5%聚氧乙烯蓖麻油。给药14 d后解剖鼠并以静脉灌注法收集成虫,计算减虫率及吡喹酮对虫株的ED50值。取经12轮亚治疗剂量吡喹酮诱导筛选的日本血吸虫吡喹酮抗性株,置实验室经小鼠⁃钉螺循环常规传代,取子8代日本血吸虫尾蚴感染实验鼠,测定吡喹酮对此子代成虫的ED50值。结果　日本血吸虫吡喹酮抗性株与敏感株尾蚴按1∶1混合感染小鼠后,吡喹酮对子8代成虫ED50值为135.2 mg/kg;日本血吸虫吡喹酮抗性株与敏感株尾蚴按2∶1混合感染小鼠后,吡喹酮对子8代成虫ED50值为129.2 mg/kg;日本血吸虫吡喹酮抗性株未予吡喹酮压力传代,吡喹酮对子8代后成虫ED50值为208.4 mg/kg。 结论　与实验室诱导的抗性株相比,日本血吸虫吡喹酮抗性株与敏感株尾蚴混合感染同一宿主后所获的子代成虫对吡喹酮抗性有所降低。日本血吸虫吡喹酮抗性株不经药物压力传代,其子代成虫仍可能够维持对吡喹酮的抗性。     

三苯双脒、青蒿琥酯、蒿甲醚和吡喹酮单剂、多剂或联合用药治疗大鼠华支睾吸虫感染的实验研究

目的 观察三苯双脒、青蒿琥酯、蒿甲醚、或吡喹酮单剂、多剂给药,及其伍用治疗感染华支睾吸虫大鼠的疗效。 方法 147只SD大鼠各感染50个华支睾吸虫囊蚴,于感染后42～44 d分组治疗。各药物采用灌胃给药。①60只感染大鼠随机分为11组（每组4～5只）,分别为三苯双脒150 mg/kg（顿服）、75 mg/（kg·d）×2 d、50 mg/（kg·d）×3 d和25 mg/kg（tid）×2 d组;吡喹酮150 mg/kg（顿服）、75 mg/（kg·d）×2 d和25 mg/kg（tid）×2 d;青蒿琥酯或蒿甲醚75 mg/kg（顿服）和37.5 mg/（kg·d）×2 d组。②另87只感染大鼠随机分为15组（每组4～6只）,用青蒿琥酯或蒿甲醚（30 mg/kg）分别与吡喹酮（150 mg/kg）、三苯双脒（50 mg/kg和75 mg/kg）伍用组;三苯双脒（50 mg/kg）与吡喹酮（150 mg/kg）伍用组;三苯双脒（75 mg/kg）与吡喹酮（187.5 mg/kg）伍用组,及各药的单用组。并设同批感染未治疗对照组。受治鼠于治疗后2周剖杀,收集胆管和肝组织内的残留华支睾吸虫,计算各组的平均虫数和减虫率,用非参数统计方法（Mann-Whitney秩和检验）对相应组间的平均虫数进行分析。 结果 感染华支睾吸虫的大鼠口服单剂三苯双脒或吡喹酮（150 mg/kg）的减虫率分别为57.2%和63.8%。三苯双脒各小剂量多次给药组的减虫率稍高,达77.1%～79.4%,而吡喹酮小剂量多次给药组的减虫率则为50.6%～54.2%。但两种药物各组间的平均虫数的差异无统计学意义。青蒿琥酯和蒿甲醚各单剂给药组与小剂量多次给药组的减虫率均较高,分别为90.4%～98.5%和100%。三苯双脒小剂量（50或75 mg/kg）与吡喹酮（150 mg/kg 或187.5 mg/kg）伍用治疗,减虫率为74.9%～100%,高于其各单药组的减虫率（26.9%～79.6%）。青蒿琥酯或蒿甲醚小剂量（30 mg/kg）与吡喹酮（150 mg/kg）或三苯双脒（50或75 mg/kg）伍用治疗,减虫率为74.9%～97.9%,亦高于其各药组的减虫率（24.8%～79.6%）。 结论 青蒿琥酯、蒿甲醚、吡喹酮和三苯双脒均为有效的抗华支睾吸虫药物,各药物小剂量伍用具有增效作用。     

Randomized,double-blind,placebo-controlled trial of oral artemether for the prevention of patent Schistosoma haematobium infections

Artemether is an efficacious antimalarial drug that also displays antischistosomal properties. Laboratory studies have found that artemether curtails the development of adult worms of Schistosoma japonicum, S. mansoni and S. haematobium, and thus prevents morbidity. These findings have been confirmed in clinical trials for the former two parasites; administered orally once every 2-3 weeks, artemether significantly reduced the incidence and intensity of patent infections. Here, we present the first randomized, double-blind, placebo-controlled trial of artemether against S. haematobium, done in a highly endemic area of C?te d'Ivoire. Urine specimens from 440 schoolchildren were examined over 4 consecutive days, followed by two systematic praziquantel treatments 4 weeks apart. S. haematobium-negative children were randomized to receive 6 mg/kg artemether (N = 161) or placebo (N = 161). Medication was administered orally for a total of six doses once every 4 weeks. Adverse events were assessed 72 hours after medication, and perceived illness episodes were monitored throughout the study period. Incidence and intensity of S. haematobium infections, and microhematuria and macrohematuria were assessed 3 weeks after the final dosing. We also monitored malaria parasitemia and treated positive cases with sulfadoxine-pyrimethamine (SP). Oral artemether was well tolerated. The incidence of patent S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08-0.38, P = 0.007). The geometric mean infection intensity in the artemether group was less than half that of the placebo recipients (3.4 versus 7.4 eggs/10 mL urine, P < 0.001). Heavy S. haematobium infections, microhematuria and macrohematuria, and the incidence of malaria parasitemia were all significantly lower in artemether recipients. In conclusion, previous findings of efficacy of artemether against S. japonicum and S. mansoni were confirmed for S. haematobium, although the protective efficacy was considerably lower. These findings enlarge the scope and potential of artemether and further contribute to discussions of its role as an additional tool for integrated schistosomiasis control.     

青蒿琥酯对日本血吸虫作用的研究Ⅰ小鼠体内不同发育阶段虫体对青蒿琥酯的敏感性

目的观察小鼠体内不同发育阶段日本血吸虫童虫与成虫对青蒿琥酯的敏感性.方法用定量日本血吸虫尾蚴感染小鼠,感染2 h,1、3、7、12、14、16、25、35 d和42 d分别一次性灌服500 mg/kg青蒿琥酯.给药后4周解剖小鼠,采用门静脉灌注法收集虫体,计算减虫率.结果青蒿琥酯对1、3、7、12、14、16、25、35、42 d龄童虫或成虫的减虫率分别为16.9%、18.0%、71.3%、50.2%、36.9%、31.3%、45.3%、58.0%、26.4%,其中以7～35 d龄虫对该药最敏感.结论青蒿琥酯对小鼠体内日本血吸虫不同发育阶段均有杀灭作用,对7～35 d龄虫体杀灭效果更为明显.     

Failure to induce resistance of Schistosoma japonicum to praziquantel

In order to explore the possible occurrence of inducing resistance of Schistosoma japonicum to praziquantel (PZQ), a set of animal experiments were carried out. Outbred mice (NIH strain), Anhui isolates of S. japonicum and Oncomelania hupensis were used. In one protocol five weeks after being infected with 48-52 cercariae, mice were orally dosed with PZQ 300 mg/kg, and killed 82 days later to isolate eggs from the liver. Snails were exposed to miracidia released from egg-hatching. F1 progeny were thus obtained through cercarial inoculation. The same scheme was applied for the establishment of the F2 generation. In another protocol two weeks after infection, PZQ 50 mg/kg/day was given to mice for 5 days. Eggs were collected 26-27 days post treatment and the identical procedures were adopted for F1 and F2 generations successively. Analysis of total worm and female worm reduction rates indicated that there was no significant difference between the sensitivity to PZQ of F1 and F2 progenies of S. japonicum and the parent worms.     

吡喹酮影响日本血吸虫病兔血清Ca2+变化的实验研究

目的：探讨吡喹酮用药前后血清Ca^2 浓度的变化并观察疗效。方法：使用吡喹酮100mg/kg和50mg/kg剂量于用药前后不同时间取血清检测Ca^2 浓度，用灌流法检获虫体，计算减虫率及减雌率。结果：不同剂量用药后2，4，8，24h的血清Ca^2 浓度均明显低于正常水平，30d后血清Ca^2 浓度基本恢复正常；100mg/kg剂量减虫率为89．7％，50mg/kg为72．2％，减雌率均为100％，结论：日本血吸虫病兔经吡喹酮治疗期间的血清Ca^2 浓度低于正常。     

花生四烯酸对小鼠日本血吸虫病治疗效果观察

目的 观察花生四烯酸对小鼠体内日本血吸虫的杀虫效果.方法 小鼠感染日本血吸虫尾蚴后,被随机分为给药组、溶剂组和未处理组.给药组小鼠在不同给药时间点,以300 mg/kg的剂量连续2d或连续7d灌服花生四烯酸溶液,溶剂组小鼠在相应时间点灌服玉米油,各组小鼠于感染后42 d解剖,收集小鼠体内成虫、肝内虫卵并计数,计算减虫率...     

三苯双脒、青蒿琥酯和吡喹酮治疗感染华支睾吸虫金色仓鼠的疗效观察

目的 观察三苯双脒、青蒿琥酯和吡喹酮对感染华支睾吸虫金色仓鼠的疗效。 方法 93只仓鼠各感染30个华支睾吸虫囊蚴, 分组后灌胃顿服给药治疗, 观察各组疗效。① 31只感染仓鼠中, 20只于感染后14 d随机均分为4组, 分别为青蒿琥酯300 mg/kg组、三苯双脒100 mg/kg和200 mg/kg组、吡喹酮200 mg/kg组, 观察药物对华支睾吸虫童虫的作用;另6只于感染后24 d随机均分为2组, 分别为三苯双脒200 mg/kg组和青蒿琥酯300 mg/kg组;余5只作对照组。② 22只仓鼠于感染后28 d随机分成5组（每组4～5只）, 分别为三苯双脒25 mg/kg和50 mg/kg组、青蒿琥酯25 mg/kg组、吡喹酮50 mg/kg组, 以及对照组。③ 40只仓鼠于感染后28 d随机分成8组（每组4～6只）, 分别为三苯双脒50 mg/kg、100 mg/kg和200 mg/kg组, 青蒿琥酯100 mg/kg和200 mg/kg组, 吡喹酮100 mg/kg和200 mg/kg组, 以及对照组。各组受治鼠于治疗后2周剖杀, 收集胆道系统内的残留华支睾吸虫, 计算各组的平均虫数和减虫率。 结果 仓鼠感染华支睾吸虫囊蚴后14 d, 三苯双脒100 mg/kg和200 mg/kg组, 以及吡喹酮200 mg/kg组的平均虫数均显著低于对照组（P<0.05）, 减虫率分别为90.6%、85.9%和71.9%;青蒿琥酯300 mg/kg组平均虫数与对照组差异无统计学意义（P>0.05）。感染后24 d, 童虫已发育为成虫, 三苯双脒200 mg/kg组平均虫数显著低于对照组（P<0.01）, 减虫率为89.8%;青蒿琥酯300 mg/kg组的减虫率为100%。感染后28 d, 三苯双脒25 mg/kg组平均虫数显著低于对照组（P<0.05）, 减虫率为71.8%, 剂量增至100 mg/kg时, 减虫率为100%;青蒿琥酯25 mg/kg和100 mg/kg组的减虫率分别为20.0%和56.4%, 剂量增至200 mg/kg时, 减虫率为98.5%, 其平均虫数显著低于对照组（P<0.01）。吡喹酮100 mg/kg和200 mg/kg组的减虫率分别为78.9%和83.5%, 其平均虫数均与对照组的差异有统计学意义（P<0.05）。 结论 三苯双脒和吡喹酮对感染华支睾吸虫童虫和成虫的仓鼠均有较好的疗效, 青蒿琥酯仅对成虫有效。     

Susceptibility of Schistosoma japonicum to praziquantel in China

To look for possible evidence of the development of resistance in Schistosoma japonicum to praziquantel, we conducted a field study in China. During the non-transmission period of schistosomiasis a random sample of 2860 individuals from six villages in three provinces of China were examined using a parasitological stool examination. Of the 372 stool-positive subjects, 363 subjects were treated with a single oral dose of 40 mg/kg of praziquantel. Six to Seven weeks after treatment, of 334 subjects examined using the same stool examination, stool-negative results were found in 319 patients which represents a 95.5% parasitologic cure rate. Fifteen subjects still excreting eggs were treated a second time with the same dose of praziquantel. All stool samples, including those from participants re-treated with praziquantel, were re-examined 12 weeks after the first treatment and no stool-positive subjects were found. The results indicate that there was no evidence for reduced susceptibility of S. japonicum to praziquantel despite its extensive use in the main endemic areas of China for more than 10 years. The in vitro responses to praziquantel of cercariae, miracidia and eggs of S. japonicum compared with S. mansoni demonstrate that the cercariae, miracidia and eggs of S. japonicum are more sensitive to praziquantel than those of S. mansoni. More sensitive worms would be less likely to develop resistance and this could explain why no evidence for resistance was found in S. japonicum in China.     

Histopathological changes in juvenile Schistosoma haematobium harboured in hamsters treated with artemether

Histopathological changes in juvenile Schistosoma haematobium, caused by artemether administered to the infected hamsters, were studied. Hamsters were infected with S. haematobium cercariae, and after 28 days, a single dose of artemether (300 mg/kg) was administered intragastrically. After 24 h, 72 h and 7 days, groups of two hamsters were sacrificed, and livers were removed, fixed and processed routinely, and examined by light microscopy. After 24 h, 93% of the schistosomulae examined showed degeneration, which included swelling of the tegument, adherence of inflammatory cells to the damaged tegument, collapsed and damaged intestine, and infiltration of inflammatory cells, predominantly lymphocytes. After 72 h, the intensity of damage increased, including severe swelling of the tegument, loss of definition in the internal structures, collapse of intestine accompanied by release of pigment particles to the parenchymal tissues, and emergence of dead schistosomulae. Seven days after treatment, the number of dead schistosomulae increased, and most of them developed to an early- or late stage of dead worm granuloma. Meanwhile, 12% of the schistosomulae showed a normal appearance, which suggested that those schistosomulae that had survived the treatment were recovered to normal. The results demonstrated that artemether effectively acts against the juvenile stages of S. haematobium and confirms earlier results with S. japonicum and S. mansoni.     

吡喹酮透皮给药对日本血吸虫成虫的治疗效果

摘要： 目的 本文旨在探究吡喹酮（Praziquantel,PZQ）透皮剂不同透皮剂量和次数的治疗效果,以及吡喹酮透皮剂对发育成熟前后日本血吸虫的治疗效果,为日本血吸虫病提供更加便利的治疗途径。方法 试验中每组昆明小鼠均感染日本血吸虫尾蚴40±2条,感染后21d、28d和35d采用不同透皮剂量的吡喹酮透皮剂和不同透皮次数治疗昆明小鼠,各试验组均设对照组,感染后42d解剖冲虫,计算减虫率、减肝卵率和减毛蚴孵化率,评价透皮剂的治疗效果。结果 感染日本血吸虫35d后吡喹酮透皮剂透皮高剂量减虫率为56.92%,低剂量透皮3次减虫率为56.15%,效果较好,减肝卵率都在70%以下;对21d、28d透皮三次的减虫率都在65%以上,减肝卵率基本接近100%。结论PZQ透皮制剂对日本血吸虫有一定的杀灭作用,杀灭效果具有剂量和次数依赖性,少量多次治疗效果较好。     

Triclabendazole and its two main metabolites lack activity against Schistosoma mansoni in the mouse model

Some have claimed that triclabendazole, a safe and efficacious drug for the treatment of fascioliasis, also exhibits antischistosomal properties, but results are conflicting. We assessed the effect of triclabendazole and its two main metabolites against two different strains of Schistosoma mansoni harbored in mice. Low worm burden reductions (18.6-35.9%) were observed in mice infected with an Egyptian strain of S. mansoni and treated with a single dose of 120 mg/kg 3 days before infection or single/double doses of 120-200 mg/kg 7 weeks after infection. Triclabendazole failed to significantly reduce hepatic and intestinal tissue egg loads, and eggs of all developmental stages were observed. Administration of 400 mg/kg of either triclabendazole, triclabendazole sulphone, or triclabendazole sulfphoxide to mice infected with a Liberian strain of S. mansoni resulted in worm burden reductions < 10%. In comparison, high worm burden reductions (82-100%) were observed in S. mansoni-infected mice treated with single oral doses of 400, 500, or 500 mg/kg twice a day praziquantel, regardless of the S. mansoni strain. We conclude that triclabendazole and its main metabolites display weak and inconsistent schistosomicidal activities.     

Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence

This paper summarizes and concludes in-depth field investigations on suspected resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70-90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitologically negative 12 weeks after treatment, although the reduction in mean egg counts was within normal ranges (86%). Among other hypotheses to explain the observed low cure rate in this focus, the possibility of drug resistance or tolerance had to be considered. Subsequent field trials with a shorter follow-up period (6-8 weeks) yielded cure rates of 31-36%. Increasing the dose to 2 x 30 mg/kg did not significantly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resulted in a normal cure rate of 79%. The efficacy of praziquantel in this focus could be related to age and pre-treatment intensity but not to other host factors, including immune profiles and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an urban region with no transmission, and re-treatment after 3 weeks of non-cured individuals within the area resulted in normal cure rates (78-88%). The application of an epidemiological model taking into account the relation between egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reduction after treatment with praziquantel; in average endemic situations, such a drug efficacy would result in normal cure rates. Laboratory studies by others on the presence or absence of praziquantel resistance in Senegalese schistosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel-resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and intense transmission in this area.