阿苯达唑对曼氏裂头蚴感染小鼠的疗效观察

为观察不同剂量阿苯达唑对感染曼氏裂头蚴小鼠的疗效,将72只小鼠随机均分为A～H等8组,每鼠经口感染5条裂头蚴。感染后1周,A～C组小鼠应用阿苯达唑灌胃治疗1个疗程(2次/d×7d),阿苯达唑1个疗程的总剂量分别为1700、2500和3300mg/kg,治疗后1周剖杀;E～G组小鼠治疗1个疗程后间隔7d,再治疗1个疗程,总剂量同A～C组,第2疗程结束后1周剖杀;D、H组小鼠仅灌服蒸馏水,分别作为A～C组和E～G组小鼠的对照组。检获裂头蚴,计算各组小鼠的平均虫数和减虫率。结果发现,A～C组小鼠的减虫率分别为20.0%、20.0%和24.9%,差异无统计学意义(χ~2=0.351,P>0.05)。E～G组小鼠的减虫率分别为22.3%、36.4%和31.9%,差异亦无统计学意义(χ~2=1.812,P>0.05);应用相同阿苯达唑剂量治疗1个与2个疗程后,小鼠减虫率的差异均无统计学意义(P>0.05)。表明阿苯达唑对裂头蚴感染小鼠无明显的治疗效果。     

Therapeutic effect of subcurative dose praziquantel on Schistosoma mansoni infected mice and resistance to challenge infection after treatment

The therapeutic effect of a subcurative dosage of praziquantel (PZQ) on Schistosoma mansoni infected mice and resistance to challenged worm infection after treatment were assessed and compared with conventional treatment using a curative dosage of PZQ. S. mansoni infected mice were treated with PZQ at a curative dosage (600 mg kg(-1)) or a subcurative dosage (300 mg kg(-1)) at 9 weeks after infection. Untreated mice and non-infected mice were added as controls. The therapeutic effect of the drug was evaluated in terms of the mortality of mice after treatment, and the parasitological and pathological findings in mice sacrificed at 1 week, 1 month, or 3 months after treatment. Another sample of mice was not killed but challenged with S. mansoni cercariae at 1 week, 1 month, or 3 months after treatment. Resistance to re-infection was evaluated by the extent of challenged worm reduction. In conclusion, there was no significant difference in mortality, or parasitological and pathological findings between mice treated with PZQ at the two dosages. However, resistance to challenged worm infection was more sustained in the group treated with subcurative dose PZQ, especially at 3 months after treatment.     

吡喹酮对曼氏裂头蚴感染小鼠治疗效果的进一步观察

目的进一步观察吡喹酮对曼氏裂头蚴感染小鼠的疗效。方法将72只小鼠分为8组（每组9只）,每只小鼠经口感染5条裂头蚴,感染后1周1-3组分别应用2 000、2 800、3 600mg/kg吡喹酮治疗1个疗程（每日3次,疗程3d）后1周剖杀,4-6组治疗2个疗程后1周剖杀,7、8组为对照组。另选40只小鼠分为4组（每组10只）,每只经口感染5条裂头蚴,感染后14周1～3组应用2 000mg/kg吡喹酮治疗后1、3、5周剖杀;4组为对照组。各组小鼠剖杀后收集裂头蚴数并计算各组的平均检出虫数和减虫率,光镜下观察虫体形态变化。结果小鼠感染裂头蚴后1周,应用2 000、2 800、3 600mg/kg吡喹酮治疗1个疗程后的减虫率分别为70.6%、77.3%及84%（P〉0.05）,治疗2个疗程后的减虫率分别为57.1%、54.6%及54.6%（P〉0.05）。小鼠感染裂头蚴后14周,应用2 000mg/kg吡喹酮治疗后1、3及5周的减虫率分别只有28%、20%及20%（P〉0.05）;虽然治疗后裂头蚴虫体有断裂现象,体壁上出现突起、溃烂及溶解等,但虫体头部无明显破坏。结论增加剂量与疗程不能提高吡喹酮对裂头蚴感染小鼠的疗效;吡喹酮对裂头蚴病的治疗效果可能与感染后的治疗时间有关。     

口服三苯双脒不同疗程抗小鼠旋毛虫成囊期幼虫的效果观察

目的比较以不同疗程口服300mg/（kg.d）三苯双脒抗小鼠横纹肌中旋毛虫成囊期幼虫的效果。方法 40只8周龄BALB/c小鼠被随机均分为5组,每只小鼠口饲感染旋毛虫成囊期幼虫50条。感染后第29d,分别以不同疗程（连续给药2、4、6、8 d）口服三苯双脒300mg/（kg.d）治疗,对照组不治疗。记录小鼠健康状况。停药后第7d,颈椎脱臼处死小鼠。肌肉压片法观察小鼠膈肌、咬肌、胸肌、腓肠肌中成囊期幼虫存活情况,计数总虫数、活虫数和死虫数。另取40只8周龄BALB/c小鼠,随机均分为5组,分别用不同疗程治疗后的小鼠膈肌成囊期幼虫50条口饲感染,感染后第29d,肌肉压片法计数膈肌中成囊期幼虫。结果实验期间,各组小鼠健康状况良好,未见药物不良反应。随着疗程的增加,4个部位肌肉中幼虫总虫荷和活虫数均呈下降趋势,而死虫数呈上升趋势。与对照组相比,2 d及2 d以上疗程组膈肌、咬肌和腓肠肌中成囊期幼虫总虫数和存活虫数均显著减少（P〈0.05、P〈0.01）,6 d疗程组和8 d疗程组胸肌总虫数显著减少（P〈0.05、P〈0.01）。随着疗程的增加,膈肌、咬肌、胸肌和腓肠肌的幼虫死亡率呈上升趋势,其中6 d疗程组分别为96.16%、98.06、99.13%和98.56%（P〈0.01）,8 d疗程组为99.62%~100%（P〈0.01）。疗效验证性感染表明,6 d（37.5%）和8 d（12.5%）的感染率显著低于对照组（100%）和2 d（100%）疗程组（P〈0.01）。2 d及以上疗程组小鼠平均虫荷和平均减虫率均显著低于对照组（P〈0.01）。结论口服TBD 300mg/（kg.d）,连续给药6 d或8 d,无不良药物反应,可有效杀死肌肉中的成囊期幼虫,为适宜疗程。     

三苯双脒对小鼠感染3个旋毛虫分离株的疗效观察

目的观察三苯双脒对感染3个分离株旋毛虫小鼠的疗效。方法将144只昆明小鼠随机均分为A组和B组,每组72只。A组小鼠再随机均分为12组,即河南分离株(以下简称河南株)、云南分离株(以下简称云南株)和黑龙江分离株(以下简称黑龙江株)旋毛虫感染组各4组,每组小鼠各感染旋毛虫分离株幼虫200条/只,感染后5 d(即成虫期)分别顿服三苯双脒10、20和30mg/kg,同时设未服药对照组。B组的分组和感染同A组,感染后53 d(即幼虫成囊期)分别灌胃三苯双脒100、200和300mg/(kg.d),1次/d×7d。A组治疗后2d处死,计数小肠内成虫数。B组治疗后10d处死,剖取全部膈肌,经消化液消化后计数幼虫。计算各组平均虫数和减虫率。结果A组中,河南株和云南株各治疗组平均虫数均低于对照组(P<0.01),河南株3个治疗组的减虫率分别为39.0%、57.9%和86.0%,云南株的减虫率分别为34.9%、69.3%和92.2%,分别随服用三苯双脒剂量的增加,减虫率呈增高的趋势,其中30 mg/kg组各有2只鼠被治愈。黑龙江株10 mg/kg组的平均虫数与对照组的差异无统计学意义(P>0.05),其他2个剂量组平均虫数均显著少于对照组(P<0.01),3组的减虫率分别为27.9%、57.4%和60.7%,亦随服用三苯双脒剂量的增加,减虫率呈增高的趋势。B组各治疗组小鼠的平均虫数均低于对照组(P<0.05),河南株的减虫率分别为57.8%、75.4%和87.5%,云南株的分别为74.5%、92.4%和99.1%,黑龙江株的分别为50.5%、53.3%和61.6%。可见3个旋毛虫感染组均随服药剂量的增加,减虫率相应增高。30 mg/kg剂量组中,云南株的减虫率与河南株的和黑龙江株的比较,差异有统计学意义(P<0.05)。结论三苯双脒对小鼠体内3个地域分离株旋毛虫成虫和成囊期幼虫均有一定的疗效,对云南株旋毛虫疗效更明显。     

不同剂量吡喹酮治疗曼氏裂头蚴感染小鼠的疗效观察

目的观察不同剂量吡喹酮对曼氏裂头蚴感染小鼠的疗效。方法156只昆明小鼠分2批感染,每只经口(灌胃)接种感染5条裂头蚴。第1批36只小鼠分为6组(每组6只),1-5组小鼠分别接种含不同浓度吡喹酮培养液中培养3d的裂头蚴,6组小鼠接种正常培养液中培养3d的裂头蚴,作为对照组;第2批120只小鼠分成12组(每组10只),分别接种青蛙或蝌蚪体内的裂头蚴,1-9组于感染后1周或5周用不同剂量的吡喹酮灌胃治疗,10-12组为对照组。各组小鼠于治疗结束后1周或2周剖杀,收集裂头蚴数并计算各组的平均检出虫数和减虫率。结果第1批小鼠接种在10-40μg/ml吡喹酮中培养3d的裂头蚴后,检出虫数与对照组相比差异无统计学意义(P0.05),接种在50μg/ml吡喹酮中培养3d的裂头蚴后,减虫率仅为16.60%,各剂量组减虫率之间差异无统计学意义(P0.05)。第2批小鼠感染青蛙体内裂头蚴1周后,用200、400、800mg/kg吡喹酮治疗后1周和2周的检出虫数与对照组相比,差异均无统计学意义(P均0.05),相同剂量组治疗后1周和2周后减虫率差异均无统计学意义(P均0.05);感染蝌蚪体内裂头蚴1周后,200、400mg/kg吡喹酮治疗后1周检出虫数与对照组相比差异均无统计学意义(P均0.05),800mg/kg治疗后1周减虫率为17.02%,各剂量组减虫率之间差异无统计学意义(P0.05)。小鼠感染青蛙体内裂头蚴5周后,用1200、1800mg/kg吡喹酮治疗1周和2周后,检出虫数差异无统计学意义(P0.05),但均明显高于对照组(P均0.05),相同剂量组减虫率之间的差异无统计学意义(P0.05)。结论吡喹酮(10～50μg/ml)在体外对裂头蚴无明显杀伤作用,但大剂量(1800mg/kg)灌胃时对裂头蚴感染小鼠疗效较好。     

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.     

青蒿琥酯预防曼氏血吸虫病的实验研究

目的　研究青蒿琥酯对小鼠曼氏血吸虫病的预防作用及优化给药方案。　方法　小鼠尾部接触感染曼氏血吸虫尾蚴后口服青蒿琥酯 ,灌注法收集计数虫体数和雌虫数 ,镜检计数肝脏和肠的虫卵 ,统计减虫率、减雌率和平均产卵量 ,分析青蒿琥酯不同给药时间、剂量、疗程的预防效果。　结果　青蒿琥酯预防小鼠曼氏血吸虫病的最佳剂量为 3 0 0mg/kg ,14、2 1d童虫对药物最为敏感 ,减虫率分别为 84%和 93 %。小鼠感染 14d后每周口服 1次青蒿琥酯3 0 0mg/kg ,连续 4wk ,减虫率达 99% ;感染 14或 2 1d后每 2wk口服 1次青蒿琥酯 3 0 0mg/kg ,连续 4wk ,减虫率达 97%或 96%。各服药组平均产卵量与对照组差异具有显著性意义　结论　青蒿琥酯可杀灭曼氏血吸虫童虫 ,影响雌虫发育产卵 ,有效预防曼氏血吸虫病。建议应用青蒿琥酯预防曼氏血吸虫病的给药方案为感染 14或 2 1d后首服 ,每 1或 2周服用 1次。     

Autoradiographic analysis of Schistosoma mansoni migration from skin to lungs in naive mice. Evidence that most attrition occurs after the skin phase

A study was performed to determine the extent of attrition of Schistosoma mansoni in naive mice (innate resistance) during the 1st week of infection. Each mouse was exposed to exactly 50 cercariae radiolabeled with [75Se] selenomethionine. On 1, 4, and 7 days postexposure, skin, lungs and liver were analyzed by compressed organ autoradiography for the presence of labeled larvae. Using this technique it was determined that no more than one-third of the 59% attrition that occurred between the cercarial and adult worm stages could be attributed to losses during the skin phase; most of the attrition in naive mice occurred after the migration of larvae to 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.     

Schistosoma mansoni: histological analysis of the synergistic interaction between vaccine immunity and praziquantel therapy in the lungs of mice

Naive CBA mice and mice vaccinated 4 weeks previously with gamma-irradiated cercariae of S. mansoni were challenged percutaneously with normal cercariae and then treated with 500 mg/kg body weight of Praziquantel (Pzq). The drug was administered intradermally on day 1 or intramuscularly on day 6, thus targeting against skin stage or lung stage challenge larvae respectively. The skin site of challenge and/or the lungs were removed at various time points to provide samples for histological examination. As reported elsewhere (Flisser, Delgado & McLaren 1989) the efficacy of Pzq was significantly enhanced in vaccinated mice and was influenced by the treatment regime. Histological analysis revealed that when Pzq was administered I/D on day 1 to vaccinated mice, the inflammatory response to challenge differed in extent but not nature from that seen in vaccinated but untreated cohorts. This correlates with worm recovery data showing no (this study), or only marginal synergy between drug treatment and immunity using this regimen of drug treatment (Flisser et al. 1989). Following the day 6 protocol of drug delivery, however, lungs from treated vaccinated mice exhibited many large inflammatory reactions containing trapped challenge larvae. In contrast, lungs from untreated vaccinated mice had only few foci which were small and rarely contained trapped larvae. These data again correlate well with worm recovery data showing that there is a highly significant synergy between vaccination and drug treatment administered at this time (Flisser et al. 1989; this study). It would seem, therefore, that Pzq exacerbates lung phase immunity in the NIMR vaccine mouse model where skin phase immunity predominates and pulmonary attrition is normally minimal. The results are discussed in the light of published data concerning the effector mechanisms thought to characterize skin and lung phase vaccine resistance in the murine model.     

Schistosoma mansoni: histological analysis of the synergistic interaction between vaccine immunity and praziquantel therapy in the lungs of mice

Summary Naive CBA mice and mice vaccinated 4 weeks previously with gamma-irradiated cercariae of 5. mansoni were challenged percutaneously with normal cercariae and then treated with 500 mg/kg body weight of Praziquantel (Pzq). The drug was administered intradermally on day 1 or intramuscularly on day 6, thus targeting against skin stage or lung stage challenge larvae respectively. The skin site of challenge and/or the lungs were removed at various time points to provide samples for histological examination. As reported elsewhere (Flisser, Delgado & McLaren 1989) the efficacy of Pzq was significantly enhanced in vaccinated mice and was influenced by the treatment regime. Histological analysis revealed that when Pzq was administered I/D on day 1 to vaccinated mice, the inflammatory response to challenge differed in extent but not nature from that seen in vaccinated but untreated cohorts. This correlates with worm recovery data showing no (this study), or only marginal synergy between drug treatment and immunity using this regimen of drug treatment (Flisser et al. 1989). Following the day 6 protocol of drug delivery, however, lungs from treated vaccinated mice exhibited many large inflammatory reactions containing trapped challenge larvae. In contrast, lungs from untreated vaccinated mice had only few foci which were small and rarely contained trapped larvae. These data again correlate well with worm recovery data showing that there is a highly significant synergy between vaccination and drug treatment administered at this time (Flisser et al. 1989; this study). It would seem, therefore, that Pzq exacerbates lung phase immunity in the NIMR vaccine mouse model where skin phase immunity predominates and pulmonary attrition is normally minimal. The results are discussed in the light of published data concerning the effector mechanisms thought to characterize skin and lung phase vaccine resistance in the murine model.     

妊娠对小鼠旋毛虫感染免疫应答的影响

目的 研究妊娠对小鼠旋毛虫感染免疫应答的影响。 方法 6只孕鼠分别经口感染300条旋毛虫肌幼虫,ELISA检测感染后不同时间血清抗体水平。感染后6周剖杀,消化全身肌肉计算每克肌肉虫荷（lpg）。测定孕鼠感染后1～4周血清介导的抗体依赖细胞介导的细胞毒性作用（ADCC）对成囊前期幼虫（PEL）的杀伤作用。观察孕鼠感染旋毛虫后第6、8和12天的肠道虫荷及雌虫体外生殖力指数。对6只处女鼠肌肉注射孕酮,观察其感染旋毛虫后6周的血清抗体水平与肌肉虫荷。 结果 孕鼠感染旋毛虫后2周的血清抗体水平（A492=0.113）显著高于未孕鼠（A492=0.078）（F=21.390,P＜0.05）。孕鼠感染后6周的每克肌肉虫荷（1 251±450）明显低于未孕鼠（2 310±1 123）（t=2.419,P＜0.05）。孕鼠感染后2周血清介导的ADCC导致成囊前期幼虫的死亡率（42.6%）显著高于未孕鼠（26.9%）（F=1.195,P＜0.05）。孕鼠感染后第6、8和12天的肠道虫荷与未孕鼠相比差异均无统计学意义（Z6=-1.185,Z8=-0.149,Z12=-0.0289,P＞0.05）,感染后第6和8天孕鼠与未孕鼠的雌虫生殖力指数间的差异亦无统计学意义（Z6=-0.149,Z8=-1.043,P＞0.05）。孕酮注射处女鼠感染旋毛虫后6周的血清抗体水平（A492=0.299）显著高于对照组（A492=0.191）（t=2.955,P＜0.05）,但其每克肌肉虫荷（1 457±551）与对照组（1 235±439）相比差异无统计学意义（t=0.726,P＞0.05）。 结论 妊娠在小鼠抗旋毛虫感染的免疫应答中具有协同作用,其机制可能与孕鼠感染旋毛虫后早期血清抗体水平升高及其介导的ADCC对成囊前期幼虫的杀伤作用增强等有关。     

The effect of cyclosporin A on the course of murine infection by Schistosoma mansoni

The effect of the immunomodulating substance cyclosporin A (CyA) has been evaluated in mice infected with Schistosoma mansoni. Administration of CyA at the time of infection or during the schistosomulum stage resulted in failure of the larvae to develop into adult worms. However, a serological response was noted. Administration of CyA during the establishment of the adult worm stage resulted in a reduction of the worm burden as compared to non-treated mice. The established worm pairs, however, seemed to be sterile since no eggs were demonstrated in the liver. Infection of mice with cercariae which had been exposed to CyA in vitro resulted in only a slight reduction of the worm burden for the highest concentration of CyA tested (100 micrograms/ml). The results of the study show that administration of CyA in vivo affects the host-parasite relationship in favour of the host.     

A comparison of the antischistosomal effect of levo- and dextro-praziquantel on Schistosoma japonicum and S. mansoni in mice

Praziquantel (PZQ) is a racemic compound composed of equal proportions of its optical isomers, levo- and dextro-PZQ. The efficacy of these compounds was compared with that of PZQ in mice infected with Schistosoma japonicum or S. mansoni. Mice were given 50, 2 x 50 (on consecutive days), 500, or 2 x 250 mg/kg of each compound orally 5 weeks after infection. Significant reduction of worm recovery was observed in S. japonicum infection 30 days after treatment with 2 x 50, 500, or 2 x 250 mg/kg of levo-PZQ, whereas no therapeutic effect was demonstrated with dextro-PZQ. Percent reduction in worm burden in mice treated with levo-PZQ was significantly higher than in those with PZQ at a dosage of 2 x 50 mg/kg (67.9% vs. 34.5%). Neither eggs in feces nor miracidial hatching of eggs from the livers and intestines were observed in mice treated with levo-PZQ. In S. mansoni infection, levo-PZQ showed no significant schistosomicidal effect compared with PZQ and dextro-PZQ, although there was reduction in egg counts.     

内脏幼虫移行症:犬弓首线虫幼虫对小鼠的致病作用

用犬弓首线虫感染性虫卵感染NIH小鼠,1000个虫卵/鼠,于感染后1、3、5、7、14、28、42、81天剖杀,观察幼虫在其肝、肺、脑、横纹肌等器官的分布及病理反应。感染后的前7天,幼虫主要分布在肝、肺,7天后主要在脑和肌肉。感染后的前28天为急性炎症反应,受累器官有出血及严重的炎症反应,其实质细胞有变性和坏死。晚期为慢性炎症反应过程,有典型的寄生虫性肉芽肿形成。     

Schistosoma mansoni: inflammatory foci around larvae in the peritoneal cavity of naive mice is radiosensitive

Innate attack to Schistosoma mansoni cercariae was evaluated in irradiated mice. It was observed that 70% of the larvae from mice sacrificed one day after whole body irradiation with 400 or 800 rads were surrounded by cluster reactivities, without difference from controls. Differences were apparent on day 5 after irradiation with sub lethal (400 rads) or lethal doses (800 rads) suggesting that innate defence to infection take at least 5 days to be affected by low dose whole-body radiation.     

EFFECT OF Bifidobacterium animalis ON MICE INFECTED WITH Strongyloides venezuelensis

The administration of viable Bifidobacterium animalis was tested to induce resistance against Strongyloides venezuelensis infection in mice. Effects on parasite burden, worm length, egg output, and intestinal mucosal histology were evaluated. The oral administration of B. animalis, strain 04450B, starting 14 days before the inoculation of nematode larvae significantly decreased the worm burden and egg output. In probiotic treated animals, the percent reduction of adult worms in the intestine was of 33% and the reduction of egg production was of 21%, compared with those of the control group. The duodenum villous height and villous/crypt ratio were significantly higher in probiotic-treated mice, indicating that this group could be experiencing less intestinal damage. The present findings revealed that the administration of B. animalis for the amelioration of host response to nematode infections is biologically plausible and could have some potential for impacting public health. Meanwhile, further study is needed to delineate the nature and identity of the factor(s) involved in these beneficial effects.     

Synergistic action of cyclosporin A and polyspecific rabbit anti-sera against murine Schistosoma mansoni

The efficacy of cyclosporin A (CsA) treatment against Schistosoma mansoni in mice was compared with treatments that included co-administration of one of two anti-sera (infected rabbit serum (IRS) obtained by repeated infection and a worm membrane antigen anti-serum (WSS) obtained by immunization with worm surface supernatants). These two sera recognized a number of worm antigens but differed in precise detail. Administration of CsA alone to mice harbouring mature infections of S. mansoni reduced worm burdens and preferentially targeted female worms. Sera administered alone had no effect on worm burdens. Co-administration of worm membrane antigen anti-serum (WSS) with CsA reduced worm burden significantly compared with drug treatment alone. Male worms were more susceptible to this combined treatment regime. Anti-infection serum (IRS) had a lesser stimulatory activity in combination with CsA which was not statistically different from the effects of CsA alone on worm burdens. The data suggest that CsA-induced surface damage to the parasite may reveal specific antigens that were previously unavailable for host attack.     

Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.