日本血吸虫多次感染宿主对治疗的反应性研究

[目的]建立等量血吸虫尾蚴单次感染和多次感染的动物模型,在感染的急性期、慢性期和晚期用吡喹酮治疗,比较这两种感染方式对治疗的反应性。[方法]测量单个虫卵肉芽肿的体积;放免法检测血清中透明质酸（HA）;RT-PCR-ELISA半定量测定肝组织中的TGF-β1mRNA,比较两种感染方式治疗组和非治疗组以及治疗组间的差异。[结果]单次感染在急性期经吡喹酮治疗,肉芽肿及纤维化程度显著降低;而多次感染组经吡喹酮治疗后,肉芽肿及纤维化程度无明显改善。[结论]等量的尾蚴,单次感染的治疗效果明显优于多次感染;急性期的治疗效果显著优于慢性期和晚期。     

免疫增强剂与免疫抑制剂对吡喹酮杀血吸虫效果的影响

目的观察中药免疫增强剂和化学免疫抑制剂对吡喹酮杀血吸虫效果的影响. 方法日本血吸虫感染昆明小鼠后随机分成四组,对照组、吡喹酮治疗组、氢化可的松(免疫抑制剂) 吡喹酮治疗组、中药(免疫增强剂) 吡喹酮治疗组,分别采取相应不同的治疗方式,于吡喹酮治疗后2周剖杀小鼠,观察减虫及减卵效果;并于吡喹酮治疗前采血,用ELISA方法测定特异性抗血吸虫成虫抗原(AWA)抗体水平. 结果与对照组相比,吡喹酮治疗组、氢化可的松 吡喹酮治疗组、中药 吡喹酮治疗组减虫率分别为53.22%,35.61%,69.16%;每克肝卵减少率分别为47.08%,31.27%,63.28%.氢化可的松 吡喹酮治疗组、中药 吡喹酮治疗组与吡喹酮治疗组相比,减虫与减卵效果统计学有显著差异(P＜0.05).且各组特异性抗AWA抗体水平高低与减虫、减卵效果相一致. 结论进一步证明吡喹酮杀血吸虫作用具有免疫依赖性,而且证实中药免疫增强剂具有增强宿主特异性免疫应答,提高吡喹酮杀虫效果的作用.     

各期日本血吸虫病人治疗前后HBV感染血清标志物的比较分析

目的　了解各期血吸虫病人治疗前后 HBV感染标志物的变化。　方法　对 80例急性期、78例慢性期及 60例晚期血吸虫病人吡喹酮杀虫治疗 ,用 EL ISA法测定治疗前后 HBV5项标志物含量。　结果　急性血吸虫病人治疗前后HBV阳性率分别为 62 .5 0 %和 2 8.75 % ,慢性血吸虫病人治疗前后 HBV阳性率分别为 2 8.2 1%和 3 0 .77% ,且各项阳性率与对照人群相似 ;晚期血吸虫病人治疗前后 HBV感染标志物阳性率分别为 5 0 .0 0 %和 5 3 .3 3 % ,两者无显著性差异 ,但其小三阳阳性率治疗前后分别为 3 3 .3 3 %和 3 1.67% ,在各组病例中最高。　结论　急性血吸虫病人治疗前 HBV阳性率明显高于治疗后 ,且 HBV感染标志物组合阳性率也是治疗前高于治疗后。慢性和晚期血吸虫病人 HBV感染率治疗前后变化不大 ,但晚期血吸虫病人 HBV感染标志物小三阳和大三阳的阳性率高于慢性和急性治疗后。     

吡喹酮早期治疗预防日本血吸虫病的实验研究

采用吡喹酮５００ｍｇ／ｋｇ总量于感染血吸虫尾蚴后２１天和２５天一次灌服早期治疗小白鼠血吸虫病，结果显示感染尾蚴后２５天用药组效果明显优于２１天用药组。提示吡喹酮早期治疗预防日本血吸虫病和控制急性血吸虫病服药时间应在接触疫水２５天后为宜。     

日本血吸虫反复感染及多次治疗鼠诱生抗攻击感染的效果观察

目的观察小鼠受日本血吸虫(Sj)反复感染与用吡喹酮或青蒿琥酯多次治疗后诱生的抗攻击感染保护力。方法反复感染与多次治疗试验:设A、B两组昆明鼠,分第1、2、6周感染Sj尾蚴。A组在第1和2次感染后15min经腹部皮肤涂抹吡喹酮,并在第1和2周灌服青蒿琥酯。B组仅在第1和2周灌服青蒿琥酯。第8周两组鼠均灌服吡喹酮,第9周每组剖杀1半小鼠,观察虫荷、检测特异抗体和体外杀童虫试验。抗攻击感染试验:以反复感染与多次治疗两组为实验鼠,对照组用正常鼠,在前述试验第10周,对三组鼠攻击感染Sj尾蚴。感染后第7周解剖冲虫,观察虫荷。结果反复感染与多次治疗鼠:在A组中,未发现虫体,在B组中,发现1条虫;特异性抗体水平B组明显高于A组;两组鼠血清对童虫具有明显杀伤作用。抗攻击感染试验:与对照组比,两组实验鼠的减虫率均为33.36%,肝卵减少率分别为24.03%和56.46%。结论反复感染和多次治疗鼠模型可诱生部分抗攻击感染的保护力。     

吡喹酮预防日本血吸虫病效果观察

用吡喹酮预防日本血吸虫病２１６例，结果表明，吡喹酮在短期内能够起到的预防血吸虫感染而控制发病的作用，在多次服药与３次服药两者间的效果有显著性差异，在人群接触疫水频率极多时，多次服药法的预防作用更佳。     

富硒螺旋藻对日本血吸虫肝硬化小鼠肝组织端粒酶活性的影响

目的探讨富硒螺旋藻抑制血吸虫肝硬化组织恶性变的作用及其机制。方法 80只小鼠感染日本血吸虫尾蚴后,随机均分为A、B、C、D4组,每组20只。A组(模型组)小鼠不作任何治疗。B组小鼠(吡喹酮组)在感染尾蚴6周时予吡喹酮500 mg/(kg·d)灌胃2 d,C组小鼠在感染尾蚴6周时予富硒螺旋藻100 mg/(kg·d)(富硒螺旋藻组)灌胃8周,D组小鼠在感染尾蚴6周时予吡喹酮500 mg/(kg·d)治疗2 d后再以富硒螺旋藻100 mg/(kg·d)(富硒螺旋藻+吡喹酮组)灌胃8周。另取10只小鼠作为正常组(E组)。第14周末分别留取各组小鼠肝组织,观察肝组织病理改变,测定其肝脏MDA含量、SOD活性以及端粒酶活性与端粒酶逆转录酶(TERT)表达变化。结果与A组比较,单纯吡喹酮或富硒螺旋藻治疗均可减轻肝纤维化程度,显著升高肝组织中SOD活性、降低MDA含量以及端粒酶活性与TERT表达水平(P0.05)。与B组相比,富硒螺旋藻治疗后小鼠肝纤维化程度、SOD活性、MDA含量及端粒酶活性与TERT表达水平无明显变化(P0.05)。与B组、C组相比,D组小鼠肝纤维化程度进一步减轻,肝组织中SOD活性显著升高、MDA含量以及端粒酶活性与TERT表达水平显著降低(P0.05)。结论晚期血吸虫肝硬化组织因端粒酶活性增高具有恶变可能,富硒螺旋藻可通过降低肝组织氧化应激水平、抑制肝组织TERT表达及端粒酶活性而发挥抑制恶性变的作用。     

日本血吸虫成虫吡喹酮用药前后差异表达序列的筛选

目的应用抑制性消减杂交（SSH）技术构建吡喹酮治疗日本血吸虫感染新西兰大白兔前后肝脏内差减cDNA文库,为筛选吡喹酮治疗过程中日本血吸虫体内药物反应分子靶标奠定基础。方法日本血吸虫感染新西兰大白兔,吡喹酮治疗者为实验组,未经吡喹酮治疗者为对照组,应用PCRSelectcDNASubtraction试剂盒进行SSH分析,分别构建正向和反向消减cDNA文库,对文库进行筛选,挑取阳性克隆测序获得差异表达EST或新EST,并进行生物信息学分析。结果从2个消减文库中共筛选到39个有效阳性克隆,其中正向文库22个,反向文库17个,分析表明这些EST编码主要是一些酶及与蛋白质合成和降解相关的蛋白质。结论成功构建日本血吸虫成虫吡喹酮治疗前后消减文库,为进一步研究吡喹酮治疗血吸虫病的分子机制奠定了基础。     

吡喹酮治疗鼠血吸虫病使肝纤维化逆转

已经公认曼氏血吸虫感染鼠是研究肝纤维化过程的好模式。鼠血吸虫病肝纤维化经治疗后是否逆转的问题,不同的研究方法往往得出不同的结论,肝纤维化在治疗后是消退、可逆或相对不可逆,其中接受治疗的早晚和追踪观察的长短(受实验鼠寿命的限制)两个重要的因素。另外,研究的药物不同也可能产生不同的结果。当前,吡喹酮在临床和实验研究方面的广泛应用,也未能证明其对免疫和纤维组织的直接作用. 作者观察了吡喹酮治疗对血吸虫病鼠肝纤维化的影响。用瑞士雄性小白鼠80只(8周龄,26～32     

吡喹酮两种给药途径的对比性研究

吡喹酮两种给药途径的对比性研究汪保国，黄铭西，刘竹青吡喹酮是一种理想的抗血吸虫药物，具有疗效高、毒性小、疗程短等优点。为比较其皮肤防护剂预防日本血吸虫病的效果和吡喹酮治疗性预防日本血吸虫病的效果，特作两种途径预防效果的对比性研究，以及使用两种方法后不...     

Schistosomiasis control in Ghana: case management and means for diagnosis and treatment within the health system

An essential component of integrated schistosomiasis control as promoted by WHO is adequate clinical care for patients presenting at health care facilities. We evaluated the functioning of the Ghanaian health system for diagnosis and treatment of schistosomiasis by interviewing health workers from 70 health care facilities in 4 geographical areas in April and May 2000. Results from presentation of 4 hypothetical cases and a subsequent interview demonstrated that patients presenting with symptoms related to schistosomiasis have a small chance of receiving adequate treatment: often health workers do not recognize the symptoms, especially those of Schistosoma mansoni; patients are frequently referred for a diagnostic test or treatment with a large risk of non-compliance; and praziquantel was not available in 78% of the health care facilities with reported schistosomiasis in their coverage area. The overall cost of treatment is considerable: [symbol: see text] 2.13 for S. haematobium and [symbol: see text] 1.81 for S. mansoni patients, with drug costs contributing approximately 40% of the total cost. To better meet WHO recommendations for passive case detection as part of integrated schistosomiasis control, the Ghanaian health system needs to emphasize training of health workers in schistosomiasis case recognition and case management and increase the availability of praziquantel. Experience from other West African countries indicate that this is feasible.     

新型吡喹酮薄膜衣片治疗日本血吸虫病的副反应及疗效研究

目的 了解新型吡喹酮薄膜衣片治疗日本血吸虫病的副反应状况及治疗效果.方法 在湖北、江西、安徽血吸虫病流行区选择6～65岁的常住居民进行问卷调查、间接血凝免疫诊断试剂筛查,血检阳性者进行改良加藤法检查以确诊.对血检阳性者及部分自愿服药的正常人共计509名给服吡喹酮并调查药物的味道,对460例服药前无副反应相关症状的化疗对象随访副反应情况,对104例粪检阳性者在化疗后3个月进行疗效考核.结果 84.7%(144/170)的被调查者认为新型吡喹酮薄膜衣片没有味道或者很轻,而吡喹酮素片对照组有92.9%(315/339)的被调查者认为药物味道较重.在化疗后1～2 h,新型吡喹酮薄膜衣片化疗组副反应率为20.30%(27/133),吡喹酮素片对照组副反应率为83.18%(272/327),两化疗组间副反应率具有统计学意义(χ2=164.316,P<0.05).其中新型吡喹酮薄膜衣片化疗组在神经肌肉系统、消化系统、心血管系统的副反应率分别为15.79%(21/133)、9.77%(13/133)、2.26%(3/133),而吡喹酮素片对照组在神经肌肉系统、消化系统、心血管系统的副反应率分别为81.65%(267/327)、49.24%(161/327)、12.84%(42/327),3个系统的副反应率在两化疗组间均具有统计学意义(χ2神经肌肉系统=175.188,χ2消化系统=62.601,χ2心血管系统12.010,P值均<0.05);吡喹酮薄膜衣片化疗组、素片对照组过敏反应发生率分别为2.26%(3/133)、0.92%(3/327),两者之间无统计学意义(χ2=1.315,P=0.235).化疗后第2天吡喹酮薄膜衣片化疗组和素片对照组的副反应率分别下降为3.01%(4/133)、38.53%(126/327),两组间存在统计学意义(χ2=58.852,P<0.05).在化疗后2周新型吡喹酮薄膜衣片化疗组、素片对照组的副反应率均已分别下降为0.75%(1/133)、0.61%(2/327),两组间已无统计学意义(χ2=0.029,P=0.642).化疗后3个月新型吡喹酮薄膜衣片化疗组、素片对照组的粪检阴转率分别为84.91%(45/51)、82.135%(42/53),两组间无统计学意义(χ2=1.536,P=0.215).结论 新型吡喹酮薄膜衣片降低了味道及化疗对象的副反应发生率,其疗效与吡喹酮素片对照组等效.在进一步扩大现场验证的基础上,可在血吸虫病流行区推广使用.     

Efficacy of a combination of praziquantel and artesunate in the treatment of urinary schistosomiasis in Nigeria

The combined effects of praziquantel and artesunate in the treatment of urinary schistosomiasis were assessed among 312 randomly selected schoolchildren aged 4-20 years in Adim community, Nigeria. In the preliminary screening, infection was confirmed in 327 (38.5%) of the 850 subjects screened. Infected subjects who reported for treatment were then divided into six treatment groups of 52 subjects each; 44 subjects in each group completed their treatment regimens and submitted their urine for post-treatment assessment. Praziquantel and artesunate were administered orally at 40 mg/kg and 4 mg/kg body weight, respectively. Adverse effects due to drug reactions were assessed 72 h after medication and all perceived episodes of illness were treated. Morbidity indicators were assessed 56 days after the final dose of the drug regimens. All treatment regimens were well tolerated. The cure rates were 72.7% in the praziquantel plus placebo-treated group and 70.5% in the artesunate plus placebo group, while the artesunate plus praziquantel group had the highest cure rate (88.6%). Haematuria and proteinuria were extensively reduced after treatment with the three drug regimens. This study confirmed that the treatment of urinary schistosomiasis with the combination of praziquantel and artesunate is safe and more effective than treatment with either drug alone.     

Circulating anodic antigen levels in serum before and after chemotherapy with praziquantel in schistosomiasis mansoni

The kinetics of serum levels of circulating anodic antigen (CAA) of Schistosoma mansoni were studied in patients with intestinal schistosomiasis before and after treatment with praziquantel. Day to day fluctuation in faecal egg excretion was compared with fluctuation in antigen level in 20 patients by serum and stool examination on 3 consecutive days before treatment. Antigen levels - calculated either as absorbance value of undiluted serum or as titre - showed less fluctuation than the number of eggs per gram of faeces determined by stool examinations based on single or duplicate 25 mg Kato smears. Compared with a placebo control group of 11 individuals, there was a significant reduction in CAA level in serum of 10 patients treated with praziquantel (40 mg/kg), 10 weeks after treatment. A similar decrease in serum CAA level was observed in a group of 46 patients treated with praziquantel, 6 weeks after treatment. In both groups, patients who remained seropositive after treatment still excreted eggs in their faeces. The kinetics of the antigen decrease were studied in more detail in 20 patients in hospital. Within 10 d after treatment with a double dose of 40 mg praziquantel per kg body weight, the antigen level fell to less than 10% of the original serum level, with a CAA half-life of approximately 2 d.     

Treatment of Schistosoma mekongi with praziquantel in Cambodian refugees in holding centres in Prachinburi province,Thailand

Eighty-four cases of schistosomiasis mekongi among Cambodian refugees in holding centres in Thailand received praziquantel at 30 mg/kg body-weight orally twice in one day. Those treated were admitted to hospital in order to observe side effects for 24 hours. Assessment of the efficacy of praziquantel was based on cure rates. Side effects observed consisted primarily of abdominal pain, anorexia, nausea, emesis and headache. These were generally mild and transient. Physical signs revealed mild hepatomegaly and splenomegaly. The cure rate obtained one month after treatment was 97·5% and by 2 to 12 months after treatment reached 100%.     

Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents

Fourteen patients with active schistosomiasis mansoni in spite of previous treatment with oxamniquine and/or hycanthone were treated with praziquantel, single oral dose of 45 to 50 mg/kg body-weight. All underwent clinical, laboratory and electrocardiographic examination before and after treatment. Untoward effects (dizziness, drowziness, nausea and abdominal pain) were observed in ten. Laboratory findings disclosed no significant alteration and the electrocardiograms showed no abnormalities. Monthly follow-up examinations of 13 patients for six consecutive months showed parasitological cure in all. Before praziquantel treatment strains of Schistosoma mansoni were isolated from two patients, one treated three times with oxamniquine and the other with hycanthone once and oxamniquine twice. Progenies of these strains were maintained in Biomphalaria glabrata and mice. Groups of these infected mice were then treated with oxamniquine, hycanthone, niridazole and praziquantel and results compared with the BH strain maintained in our laboratory for many years. Schistosomicidal activity was assessed by the localization of worms in the portal vein system and oogram changes. Progenies from the strains isolated in this study were resistant to oxamniquine and hycanthone but sensitive to niridazole and praziquantel. The BH strain was sensitive to all four drugs. The serial runs of S. mansoni strains through intermediate and definitive hosts have not influenced their reactions to these schistosomicides.     

Integration of mass drug administration programmes in Nigeria: The challenge of schistosomiasis

PROBLEM: Annual mass drug administration (MDA) with safe oral anthelminthic drugs (praziquantel, ivermectin and albendazole) is the strategy for control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis. District health officers seek to integrate treatment activities in areas of overlapping disease endemicity, but they are faced with having to merge different programmatic guidelines. APPROACH: We proceeded through the three stages of integrated MDA implementation: mapping the distribution of the three diseases at district level; tailoring district training and logistics based on the results of the mapping exercises; and implementing community-based annual health education and mass treatment where appropriate. During the process we identified the "know-do" gaps in the MDA guidelines for each disease that prevented successful integration of these programmes. LOCAL SETTING: An integrated programme launched in 1999 in Plateau and Nasarawa States in central Nigeria, where all three diseases were known to occur. RELEVANT CHANGES: Current guidelines allowed onchocerciasis and LF activities to be integrated, resulting in rapid mapping throughout the two states, and states-wide provision of over 9.3 million combined ivermectin-albendazole treatments for the two diseases between 2000 and 2004. In contrast, schistosomiasis activities could not be effectively integrated because of the more restrictive guidelines, resulting in less than half of the two states being mapped, and delivery of only 701,419 praziquantel treatments for schistosomiasis since 1999. LESSONS LEARNED: Integration of schistosomiasis into other MDA programmes would be helped by amended guidelines leading to simpler mapping, more liberal use of praziquantel and the ability to administer praziquantel simultaneously with ivermectin and albendazole.     

The effect of different anthelmintic treatment regimens combined with iron supplementation on the nutritional status of schoolchildren in KwaZulu-Natal, South Africa: a randomized controlled trial

A randomized controlled trial in KwaZulu-Natal (South Africa) of 428 primary-school pupils (stratified into 6 groups by age, sex and intervention) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year (1996/97). Half the pupils received iron supplementation (ferrous fumarate 200 mg weekly for 10 weeks). Pupils received 2 anthelmintic regimens, either (i) albendazole 400 mg plus praziquantel 40 mg/kg or (ii) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or (iii) placebo. Baseline prevalences of Ascaris 55.9%, Trichuris 83.6%, hookworm spp. 59.4%, were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4% (P < 0.005), Trichuris 61.5% (NS), hookworm spp. 0% (P < 0.005), and for triple-dose albendazole treatment to Ascaris 14.8% (P < 0.005), Trichuris 25.0% (P < 0.01), hookworm 0% (P < 0.005). Schistosoma haematobium 43.4% was reduced among treated groups to 8.3% (P < 0.005). There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment. Twelve months after treatment there was a significant increase in haemoglobin levels (P = 0.02) among pupils receiving triple-dose albendazole, praziquantel and ferrous fumarate; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron. Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris, hookworm spp. and S. haematobium infections (P < 0.05). Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg (P = 0.002). In areas with schistosomiasis, hookworm infection and high prevalence of Trichuris infection, combination treatment with praziquantel, triple-dose albendazole, plus iron supplementation, is likely to improve pupils' health and haemoglobin levels.     

The impact of a school health programme on the prevalence and morbidity of urinary schistosomiasis in Mwera Division, Pangani District, Tanzania

The prevalence of urinary schistosomiasis among schoolchildren in Pangani District (Tanzania) was assessed rapidly by a questionnaire approach. Based on the results, a strategy of selective treatment with praziquantel was adopted. Eleven primary schools in Mwera Division, Pangani District, with about 2500 schoolchildren were included in a control programme for urinary schistosomiasis. Macro- and microscopic haematuria diagnosed visually and with urine reagent strips was used as an indirect indicator of Schistosoma haematobium infection. Intensity of infection among children was monitored in class 5 (median age 14 years, range 11-17) by urine filtration techniques. Treatment was administered as 40 mg/kg praziquantel in a single dose at the beginning of the school year. The programme was implemented by schoolteachers and coordinated by the District Health Management Team in collaboration with the District Education Office. Teachers were responsible for carrying out all programme activities. Community participation was through collaboration with Teachers-Parents Associations and Village Health Committees. Coverage at yearly (1995-99) examination varied from 67.7% to 80.3%. Prevalence of haematuria decreased from 51.2% (range 22.2-89.5%) at baseline to 23.4% (range 5.8-56.7%) in 1999, a reduction of 54.3%. Macrohaematuria was 21.2% at baseline and 7.2% in 1999, a reduction of 66.0%. Prevalence of infection in class 5 was reduced by 71.4% and geometric mean intensity of positives reduced from 71 eggs/10 mL (95% confidence interval [CI] 52.5-97.7) to 28 eggs/10 mL (95% CI 25.7-55.0), a reduction of 60.6%. Teachers were highly committed, and secured community participation and a smooth implementation of the programme. The community accepted the introduction of a cost-recovery system, whereby parents pay for the treatment of children with episodes of visible haematuria during the school year. Communities also participated in the improvement of sanitary installations at the schools.     

Control of Schistosoma mekongi in Cambodia: results of eight years of control activities in the two endemic provinces

In Cambodia, schistosomiasis is transmitted in the provinces of Kratie and Stung Treng where approximately 80000 individuals are estimated to be at risk of infection. The baseline prevalence of infection was estimated to be between 73% and 88%, and cases of severe morbidity (hepatosplenomegaly, puberty retardation) and mortality were very common. In 1994, the Ministry of Health of Cambodia started schistosomiasis control applying universal chemotherapy with praziquantel (40mg/kg). The coverage of the programme was between 62% and 86% for 8 years. This simple control measure resulted in the control of the disease: no cases were reported in 2004 and only three cases were reported in 2005. In addition, there are no longer reports of cases of severe morbidity due to schistosomiasis. Since the beginning of the control programme, a single dose of mebendazole (500mg) has been combined with praziquantel during the mass chemotherapy; as a result the prevalence of Ascaris lumbricoides and hookworms dropped from 74.5% to 10% and from 86% to 40% respectively. The experience in Cambodia demonstrates that, with political commitment, control of parasitic diseases is achievable even in a situation of minimal resources. The programme represents a successful model for other developing countries.