口服青蒿琥酯早期治疗预防日本血吸虫病的实验研究

本文介绍了青蒿琥酯早期治疗预防动物血吸虫病的疗效.实验动物于感染血吸虫尾蚴后第7d开始喂服青蒿琥酯,剂量分别为小鼠300mg/kg,兔20—40mg/kg及犬30mg/kg,每wk 1次,服用4—6次,对小鼠、兔和犬的减虫率分别为77.50%—90.66%、99.53%和97.10%.青蒿琥酯能杀灭宿主体内尚未发育成熟的血吸虫,可保护肝脏免受血吸虫及其虫卵的危害.并适用于不同感染度及反复感染的实验动物.在几种青蒿素衍生物中,采用同剂量、同疗程青蒿琥酯杀童虫作用优于蒿甲醚和还原青蒿素.     

口服青蒿琥酯对日本血吸虫再感染小鼠的预防效果

目的评估口服青蒿琥酯对日本血吸虫再感染小鼠的预防效果。方法实验鼠分成4组,第一组只感染血吸虫一次,然后从感染血吸虫第7天起,口服青蒿琥酯300mg/kg。一周2次,连续2周,它的对照组只进行血吸虫感染。第三组小鼠进行再感染实验:人工感染血吸虫7天的实验鼠,口服青蒿琥酯300mg/kg。一周2次,连续2周,间隔一周后,再次感染血吸虫,服药的处理同前。最后一次服药后一周,用20条血吸虫尾蚴进行攻击感染。同时,未服药的小鼠作为对照。结果在抗再感染组,减虫率52.6％,减雌率54 3％,肝减卵率96.9％,并且,雌虫长度显著地缩小。预示雌虫的发育被阻碍。结论青蒿琥酯在预防再感染中能有效的减少雌虫和雌虫产卵量,值得进一步研究。     

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。     

双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及伍用治疗小鼠血吸虫病效果观察

目的观察双氢青蒿素、青蒿琥酯和蒿甲醚连续给药或伍用治疗小鼠血吸虫病的效果,为日本血吸虫病病原学治疗提供药物配伍实验依据。方法采用腹部贴片感染法,每鼠感染日本血吸虫尾蚴40±1条,分别于感染后6~8 d(童虫期)和34~36 d(成虫期),以300 mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及3种药物等剂量配伍给药,在感染后50 d解剖小鼠,收集成虫,计算减虫率和减雌率。结果在感染后6~8 d,双氢青蒿素、青蒿琥酯、蒿甲醚连续3 d单独给药和3种药物等剂量配伍给药,小鼠减虫率为79.5%~86.0%;减雌率为79.4%~86.7%,差异均无统计学意义(P均>0.05);在感染后34~36 d给药,减虫率为73.8%~75.8%,减雌率为88.7%~93.1%,差异无统计学意义(P均>0.05)。结论双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及伍用治疗小鼠血吸虫病效果无显著差异。     

青蒿琥酯抗日本血吸虫童虫和成虫作用的研究

目的 观察青蒿琥酯对不同阶段日本血吸虫的损害作用,揭示青蒿琥酯的杀虫机制.方法小鼠感染尾蚴18 d时给予青蒿琥酯300 mg/kg,24 h后灌注法收集童虫,并用紫外吸收法和Bradford标准曲线法测定青蒿琥酯对日本血吸虫18 d童虫DNA和蛋白质含量的影响;分别将10条虫体在含有3H胸腺嘧啶核苷的培养基中培养24 h后,用滤膜法和匀浆法测定青蒿琥酯对标记核苷掺入童虫DNA的影响;感染血吸虫尾蚴21 d的小鼠一次性灌服青蒿琥酯300 mg/kg,给药后21 d,灌注法收集成虫,观察青蒿琥酯对日本血吸虫成虫生殖器官大小及生殖细胞发育的影响;小鼠感染血吸虫33 d时给予同样的青蒿琥酯进行治疗,24 h和48 h后处死小鼠,将肝脏制作组织切片,在光镜下观察同等剂量青蒿琥酯引起的成虫肝移和形态学变化的影响.结果 青蒿琥酯体内作用18 d的虫体,24 h后,童虫的DNA和蛋白质含量均较对照组明显减少,减少率分别为23.0%和33.6%(P＜0.01);在含有3H胸腺嘧啶核苷的培养基中培养24 h后,童虫摄入标记的核苷及核苷掺入童虫DNA的量较对照组也明显减少,减少率分别为61.1%和40.8%(P＜0.01);21 d给药组小鼠体内雌虫卵巢的成熟、发育受到了抑制;药物作用于虫体33 d后能明显引起虫体形态的变化,特别是虫体体表.结论 青蒿琥酯能减少日本血吸虫童虫蛋白质和DNA的含量,能明显抑制虫体对标记核苷的摄入以及标记核苷掺入虫体DNA的量,能引起虫体体表明显的组织形态学变化,并且能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵,能有效减轻血吸虫病的病情和控制传播.     

青蒿琥酯对日本血吸虫作用的研究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2h,1、3、7、12、14、16、25、35d和42d分别一次性灌服500mg/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、42d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7~35d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7~35d龄虫体杀灭效果更为明显。     

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.     

青蒿琥酯对日本血吸虫生殖作用的影响

目的观察青蒿琥酯对日本血吸虫成虫生殖的影响。方法小鼠感染日本血吸虫尾蚴后第20d灌服青蒿琥酯300mg/kg,给药后3周解剖小鼠,用灌注法收集成虫,计算减虫率;取肝右叶做石蜡切片,观察虫卵肉芽肿;剩余肝脏溶解后计数虫卵;收集无损虫体进行体外培养,观察虫卵形态,并计数产卵量;取完好的虫体做石蜡切片,HE染色后镜下观察生殖器官的发育。结果给药组小鼠体内雌虫产卵量与对照组存在显著的差异,体外培养结果与体内产卵结果相一致。给药组小鼠体内的雌虫的卵巢发育缓慢,比对照组的小,且卵巢内多为未成熟的卵细胞。结论青蒿琥酯能抑制雌虫卵巢的发育,降低或抑制雌虫的产卵量,具有抗日本血吸虫雌虫生殖的作用,能有效的减轻血吸虫病的病情和控制传播。     

青蒿琥酯和吡喹酮防治血吸虫病相互作用的研究

本文就血吸虫病防治药青蒿琥酯与血吸虫病防治药吡喹酮的相互作用进行了初步探讨，实验结果表明：小鼠口服青蒿琥酯３００μｇ／ｋｇ对第７天、第８天的童虫有杀灭作用，减虫率为７１．６％，减雌率为７２％；口服吡喹酮３００ｍｇ／ｋｇ对第７天童虫无效，对第３０天成虫有明显杀灭作用，减虫率为７２％，减雌率为７８．３％；青蒿琥酯与吡喹酮同时服，或者先服吡喹酮后服青琥酯均明显影响青琥酯的杀童虫作用；先服青蒿琥酯而后服吡     

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.     

青蒿琥酯与吡喹酮联合应用早期治疗兔血吸虫病的实验观察

目的 观察青蒿琥酯与吡喹酮先、后使用早期治疗兔血吸虫病的效果。方法 实验共分4组，第1组于感染后第7天首服青蒿琥酯，第35天再服吡喹酮，剂量分别为20mg／kg和40mg/kg。第2组为单青蒿琥酯组，于感染后第7天首服青蒿琥酯，剂量为20mg/kg，每周服1次，连服4次。第3组为单用吡喹酮组，于感染后第35天顿服吡喹酮，剂量为40mg/kg。第4组为不服药对照组。各组于停药后4周解剖，检获成虫，比较各组的减虫率、减雌率和肝脏变化。结果 以感染后第7天首服青蒿琥酯，第35天再服吡喹酮的效果最好，减虫率为97．88％、减雌率达98．63％，6只兔中有2只无虫。单青蒿琥酯和单吡喹酮两组的减虫率分别为94．32％和71．67％，减雌率为96．14％和80．75％。结论 青蒿琥酯与吡喹酮先、后用药组明显优于吡喹酮组(P＜0．01)，但与青蒿琥酯组比较差异不显著，然而缩短了疗程，减少了费用，便于现场使用。     

Kinetics of the pulmonary phase of Schistosoma mansoni in mice treated with dexamethasone

In the experimental schistosomiasis mansoni glucocorticoids cause a reduction in the worm burden when administered in the week of infection or, the longest, at the next week. In order to determinate the probable(s) site(s) of reduction of the worm burden, mice were infected with cercariae of LE strain of S. mansoni and dexamethasone was administered daily (50 mg/kg, subcutaneously) starting 1 hour before infection until the eighth day. Mice were sacrificed daily starting on the third day after infection until the ninth day, and schistosomula from lungs were collected. Six weeks after infection, the remaining mice were sacrificed and perfused for adult worm recovery. Analysis of the results showed that the non-treated mice presented larger numbers of lung larvae than the treated ones, and this difference was also found later in the worm burden in the portal system. This difference may reflect the early death of larvae in treated animals, before or after reaching the lungs.     

Prophylactic effect of the anti-inflammatory drug diclofenac in experimental schistosomiasis mansoni.

OBJECTIVES: This study was a trial to demonstrate the prophylactic effect of diclofenac, a widely used anti-inflammatory drug (diclofenac potassium, CAS-15307-81-0, Ciba Geigy, 334.2) in experimental schistosomiasis mansoni. Two different dose regimens were used to explore the effects upon worm load, tissue egg load, and hepatic granuloma size. METHODS: In this study, a group of 50 Swiss albino mice was used. This group was divided into five subgroups: subgroup I constituted infected untreated control mice; subgroup II, infected mice given 0.5 mg diclofenac orally 24 h post infection, then sacrificed three weeks later; subgroup III, infected mice given 0.5 mg diclofenac orally six weeks post infection and sacrificed one week later; subgroup IV, infected mice administered 1mg diclofenac orally 24 h post infection and sacrificed three weeks later; and subgroup V, infected mice given 1mg of the drug orally six weeks post infection and sacrificed one week later. RESULTS: Mice given the high dose regimen (1mg orally/mouse) 24 h post infection, then sacrificed three weeks later, demonstrated a significant reduction in the immature worms recovered, compared to the untreated controls. Animals receiving the high dose of the drug six weeks post infection, then sacrificed one week later, revealed a drop in the number of mature worms and in the tissue egg load (hepatic and intestinal), and the smallest hepatic granuloma measurement compared to the untreated controls. These findings were less conspicuous in animals given the low dose regimen. CONCLUSION: Diclofenac could be used successfully as a preventive agent against schistosomiasis mansoni infection in endemic areas.     

Artemether treatment of prepatent Schistosoma japonicum induces resistance to reinfection in association with reduced pathology

Artemether (ART) is a well-described antimalarial with efficacy against juvenile schistosomes, with 7-day-old schistosomula being particularly susceptible. Both ART-affected worms and parasites developing from irradiated cercariae die at similar times after infection. Our aim was to determine if ART treatment of prepatent schistosomiasis japonica may result in the generation of a protective immune response. Female CBA mice were treated with a single dose of ART at defined time points after percutaneous infection with a virulent Chinese mainland strain of Schistosoma japonicum. Half of the mouse cohorts were subjected to homologous parasite strain reinfection after drug treatment to assess protective effects of ART therapy. Two independent trials demonstrated that a statistically significant (58% and 50%) reduction in challenge worm burden occurred after reinfection of those mice treated with ART at two weeks p.i. A reduction in the IL-4 response to soluble worm antigen preparation (SWAP) was also seen in ART-treated mice but with no correlation to reinfection resistance. In the Chinese mainland strain used, ART treatment of prepatent infection at the appropriate time point induced resistance to reinfection. There was also an anti-pathology effect observed in ART-treated mice that remained significant after reinfection.     

Protection of mice against Schistosoma mansoni infection by passive transfer of sera from infected rabbits

Sera from rabbits infected with unattenuated Schistosoma mansoni cercariae conferred significant levels of protection against S. mansoni challenge ( P  < 0.001) after passive transfer to mice. Infected rabbit sera were only effective in conferring protection when transferred during the first week of infection, and were not effective when administered against liver-stage worms. Immunoglobulins isolated from the infected rabbit sera with Protein A-Sepharose were shown to be responsible for the transfer of protection to mice. Immunofluorescence studies demonstrated that the sera were more reactive against the surface of three hour-old mechanically transformed schistosomula than against the surfaces of lung-stage schistosomula. The sera from infected rabbits reacted polyspecifically against antigens in cercaria, schistosomula, and the worm and egg stages of the S. mansoni life-cycle. The host parasite relationship of S. mansoni in the rabbit is discussed.     

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。     

The immunofluorescence antibody test (IFAT) for the diagnosis of schistosomiasis used in a non-endemic area

OBJECTIVE: To evaluate an immunofluorescence antibody test (IFAT) for diagnosis of schistosomiasis in nonimmune travellers and immigrants from endemic areas. METHODS: 65 patients (48 Danes and 17 immigrants) with schistosomiasis were included. The diagnosis of schistosomiasis was based on the presence of schistosome eggs in faeces, urine, sperm, rectal or bladder biopsies and/or the presence of specific antibodies determined by the serological immunofluorescence antibody test (IFAT). Egg excretion was detected using conventional methods and the IFAT performed on whole S. mansoni schistosomula worms, harvested after 8 weeks from mice. Two patterns of immunofluorescence were observed: Fluorescence in the gut of the schistosome called 'Gut Associated Antigen, GAA', and fluorescence of the surface of the schistosomula called 'Membrane Bound Antigen, MBA'. RESULTS: Eggs were found in 44% of the Danish patients and in 76% of immigrants. The diagnosis was based on a positive IFAT in 48% of the patients. In patients from nonendemic areas, the finding of antibodies against GAA was diagnostic while optimal sensitivity in the immigrants was reached by measuring antibodies against both GAA and MBA. CONCLUSION: In patients from nonendemic areas GAA is a sensitive marker of acute infection with schistosomiasis. In patients from endemic areas the demonstration of both GAA and MBA is necessary to properly identify long-lasting, nonacute infections. Egg-detection and/or measurement of CAA and CCA remain the methods of choice to monitor treatment as the immunofluorescence assay may remain positive for several years after treatment.