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Human immune responses to infective stage larval-specific chitinase of filarial parasite, Onchocerca volvulus, Ov-CHI-1. 人类对丝虫幼虫感染期特异性几丁质酶 Ov-CHI-1 的免疫反应。
Pub Date : 2003-03-14 DOI: 10.1186/1475-2883-2-6
Yang Wu, Gillian Egerton, James S McCarthy, Thomas B Nutman, Albert E Bianco

BACKGROUND: Ov-CHI-1 is a chitinase specifically expressed in the infective stage larvae of the human filarial parasite Onchocerca volvulus. Evidence has show that it could be a vaccine candidate, however, there is no data available regarding the immunological status of people naturally exposed to infective stage larvae and thus provoked by this antigen. METHOD: We analysed the Ov-CHI-1-specific immune response present in four endemic foci of human onchocerciasis (Ecuador, Nigeria, Togo and Cameroon) by enzyme-linked immunosorbent assays and T-cell proliferation assays. RESULTS: In these foci of infection, antibodies to Ov-CHI-1 were found to be present in only 22% of individuals from Ecuador, but were detected in 42-62% of infected individuals in the three foci from West Africa (Nigeria, Togo and Cameroon). There was found to be no relationship between antibody level and age, gender, or infection intensity as indicated by microfilarial density and numbers of skin nodules. The isotype response to Ov-CHI-1 was dominated by the presence of IgG3, IgG1 was present to a lesser extent. Our results show a positive correlation between N- and C-termini of Ov-CHI-1 in their ability to provoke humoral and cellular immune responses in the human. Peripheral blood mononuclear cell (PBMC) proliferative responses to Ov-CHI-1 when assayed, were found to be significantly higher in the individuals from endemic areas and there was a statistically elevated response to Ov-CHI-1 in the infected individuals when compared to putative immune individuals. CONCLUSION: Ov-CHI-1 is an antigen that we have found strongly induces both humoral and cellular immune responses in humans.

背景:Ov-CHI-1 是一种几丁质酶,专门在人类丝虫感染期幼虫中表达。有证据表明,它可以作为候选疫苗,但目前还没有关于自然暴露于感染期幼虫并因此被这种抗原激发的人群的免疫状态的数据。方法:我们通过酶联免疫吸附试验和 T 细胞增殖试验分析了四个盘尾丝虫病流行区(厄瓜多尔、尼日利亚、多哥和喀麦隆)的 Ov-CHI-1 特异性免疫反应。结果:在这些感染疫点中,厄瓜多尔只有22%的人体内存在Ov-CHI-1抗体,而在西非的三个疫点(尼日利亚、多哥和喀麦隆),42%-62%的感染者体内都检测到了Ov-CHI-1抗体。研究发现,抗体水平与年龄、性别或感染强度(如微丝蚴密度和皮肤结节数量)之间没有关系。对 Ov-CHI-1 的同型反应主要是 IgG3 的存在,IgG1 的存在较少。我们的研究结果表明,Ov-CHI-1 的 N 端和 C 端在引发人体体液免疫和细胞免疫反应的能力方面存在正相关。在检测外周血单核细胞(PBMC)对 Ov-CHI-1 的增殖反应时,发现来自地方病流行地区的人对 Ov-CHI-1 的反应明显较高,与假定免疫的人相比,受感染的人对 Ov-CHI-1 的反应在统计学上有所升高。结论:我们发现,Ov-CHI-1 是一种能强烈诱导人类体液和细胞免疫反应的抗原。
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引用次数: 0
Some observations on the effect of Daflon (micronized purified flavonoid fraction of Rutaceae aurantiae) in bancroftian filarial lymphoedema. 蒲公英(粉碎金缕香类黄酮提取物)对班氏丝虫病淋巴水肿作用的观察。
Pub Date : 2003-03-12 DOI: 10.1186/1475-2883-2-5
LK Das, G Subramanyam Reddy, SP Pani

BACKGROUND: Morbidity management is a core component of the global programme for the elimination of lymphatic filariasis. In a double-blind clinical trial, the tolerability and efficacy of Daflon (500 mg) + DEC (25 mg) or DEC (25 mg) alone, twice daily for 90 days, was studied in 26 patients with bancroftian filarial lymphoedema. RESULTS: None of the patients in either drug group reported any adverse reaction throughout the treatment period (90 days). Haematological and biochemical parameters were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 90) values. The group receiving Daflon showed significant reduction in oedema volume from day 90 (140.6 PlusMinus; 18.8 ml) to day 360 (71.8 PlusMinus; 20.7 ml) compared to the pre-treatment (day 0, 198.4 PlusMinus; 16.5 ml) value. This accounted for a 63.8% reduction in oedema volume by day 360 (considering the pre-treatment (day 0) as 100%). In the DEC group, the changes in oedema volume (between day 1 and day 360) were not significant when compared to the pre-treatment (day 0) value. The percentage reduction at day 360 was only 9%, which was not significant (P > 0.05). CONCLUSION: This study has shown that Daflon (500 mg, twice a day for 90 days) is both safe and efficacious in reducing oedema volume in bancroftian filarial lymphoedema. Further clinical trials are essential for strengthening the evidence base on the role of this drug in the morbidity management of lymphatic filariasis.

背景:发病率管理是全球消除淋巴丝虫病规划的核心组成部分。在一项双盲临床试验中,研究了26例bancrofftian丝状淋巴水肿患者的耐受性和疗效,研究了Daflon (500 mg) + DEC (25 mg)或DEC (25 mg)单独使用,每天两次,持续90天。结果:在整个治疗期间(90天),两组患者均未出现不良反应。血液学和生化指标均在正常范围内,治疗前(第0天)和治疗后(第90天)的数值无显著差异。从第90天开始,服用达芙莲的组水肿量显著减少(140.6±;18.8 ml)至360天(71.8±;20.7 ml)与前处理(第0天,198.4±;16.5 ml)值。到第360天,水肿体积减少了63.8%(考虑到治疗前(第0天)为100%)。在DEC组中,与治疗前(第0天)相比,水肿体积(第1天至第360天)的变化不显著。第360天降低率仅为9%,差异不显著(P > 0.05)。结论:本研究表明,达芙蓉(500mg,每日2次,连用90天)对减少班氏丝状淋巴水肿是安全有效的。进一步的临床试验对于加强该药物在淋巴丝虫病发病率管理中的作用的证据基础至关重要。
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引用次数: 25
Lymphoedema: Pathophysiology and management in resource-poor settings - relevance for lymphatic filariasis control programmes. 淋巴水肿:资源匮乏环境下的病理生理学和管理——与淋巴丝虫病控制方案的相关性。
Pub Date : 2003-03-12 DOI: 10.1186/1475-2883-2-4
Babar Vaqas, Terence J Ryan

Low cost reduction of morbidity in lymphoedema is an essential goal in the management of lymphatic filariasis. This review emphasises the role of movement and elevation, and refers to the literature on the effects of these on the venous and lymphatic system. The patient with lymphoedema becomes increasingly immobile and the affected limb is often in a permanently dependent position causing venous hypertension and resultant overloading of the failing lymphatics. The evidence that breathing exercises are important for reducing venous hypertension and inducing lymphatic flow is discussed.The contribution of a damaged epidermis to lymphatic failure is emphasised. Loss of barrier function encourages penetration of bacteria and stimulates repair mechanisms that generate cytokines, which, in turn lead to inflammation. Management programmes that improve the health of the epidermis play a part in reducing lymphatic load.In taking morbidity management of lymphoedema into the general health services there are benefits in promoting skin hygiene and self-help regimes that can ameliorate many diseases along with lymphoedema.

低成本降低淋巴水肿的发病率是淋巴丝虫病治疗的一个重要目标。这篇综述强调了运动和抬高的作用,并参考了有关这些对静脉和淋巴系统影响的文献。淋巴水肿患者变得越来越不动,受影响的肢体经常处于永久依赖性位置,导致静脉高压,并导致衰竭的淋巴管过载。讨论了呼吸练习对降低静脉高压和诱导淋巴流动很重要的证据。强调了受损表皮对淋巴管衰竭的影响。屏障功能的丧失会促进细菌的渗透,并刺激产生细胞因子的修复机制,进而导致炎症。改善表皮健康的管理方案在减少淋巴负荷方面发挥了作用。将淋巴水肿的发病率管理纳入一般卫生服务中,有利于促进皮肤卫生和自助制度,可以改善许多与淋巴水肿相关的疾病。
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引用次数: 76
Animated documentation of the filaria dance sign (FDS) in bancroftian filariasis. 班氏丝虫病中丝虫舞征(FDS)的动画记录。
Pub Date : 2003-02-27 DOI: 10.1186/1475-2883-2-3
Sabine Mand, Yeboah Marfo-Debrekyei, Matthias Dittrich, Kerstin Fischer, Ohene Adjei, Achim Hoerauf

BACKGROUND: Ultrasonography is able to detect adult Wuchereria bancrofti worms in scrotal lymphatic vessels of infected men on account of the characteristic pattern of adult worm movements, known as the filarial dance sign. Furthermore, the technique is able to delineate associated pathology, such as hydrocoele and lymphoedema, which can be diagnosed in early stages. Ultrasonography is also useful in the assessment of macrofilaricidal effects of antifilarial medication.The purpose of this study was to evaluate the usefulness of scrotal ultrasonography, in combination with a new method of digital documentation, in men infected with Wuchereria bancrofti. METHODS: Ultrasonography of the scrotal areas was carried out in 33 male patients from an endemic area in Ghana using a hand-carried ultrasound system and a linear array transducer at 7.5 MHz. Wuchereria bancrofti infection was also assessed by quantification of night blood microfilaraemia and semi-quantitative detection of circulating filarial antigen. Ultrasound findings were documented by print outs and by Digital Video sequences directly exported from the ultrasound machine which were edited in Final Cut Pro 3ledR; and exported, using QuickTimecircledR; Pro, as MPEG-1 video. RESULTS: Worm nests, i.e. dilated lymphatic vessels with the characteristic movement patterns of worms, were found in all patients, and typical examples of larger as well as smaller nests are presented through MPEG-1 video in b- and m-modes as well as Colour Doppler and Pulse Wave Doppler images. CONCLUSION: In this study, the filarial dance sign is being made available on the Internet to readers through MPEG-1 video. This method allows for demonstration of movement patterns rather than static images. In addition, the pathologic ultrasonographic signs of filariasis can be rapidly relayed over great distances and may be helpful to other investigators or clinicians in the diagnosis of patients infected with Wuchereria bancrofti.

背景:由于成虫运动的特征性模式,被称为丝虫舞征,超声检查能够在感染男性的阴囊淋巴管中检测到成虫。此外,该技术能够描述相关病理,如腔积水和淋巴水肿,可以在早期诊断。超声检查在评估抗丝虫药的大丝虫病效果方面也很有用。本研究的目的是评估阴囊超声检查结合一种新的数字记录方法对男性感染班氏乌切里氏菌的有用性。方法:对来自加纳某流行地区的33例男性患者进行阴囊超声检查,使用手持式超声系统和7.5 MHz线性阵列换能器。采用夜血微丝虫病定量和循环丝虫病抗原半定量检测评价班氏乌chereria bancroti感染。超声结果通过打印输出和直接从超声机导出的数字视频序列记录,这些序列在Final Cut Pro 3ledR中编辑;并导出,使用QuickTimecircledR;Pro,作为MPEG-1视频。结果:所有患者均可见蠕虫窝,即淋巴血管扩张,具有蠕虫特有的运动模式,通过MPEG-1视频在b和m模式下以及彩色多普勒和脉冲波多普勒图像显示了典型的大巢和小巢。结论:在本研究中,丝状舞蹈符号通过MPEG-1视频在互联网上提供给读者。这种方法允许演示运动模式,而不是静态图像。此外,丝虫病的病理超声征象可以远距离快速传递,可能有助于其他研究人员或临床医生诊断感染班氏乌切利菌的患者。
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引用次数: 64
Final report of the Conference on the eradicability of Onchocerciasis. 消灭盘尾丝虫病会议的最后报告。
Pub Date : 2003-02-07 DOI: 10.1186/1475-2883-2-2
Yankum Dadzie, Maria Neira, Donald Hopkins

Sixty-four experts from a variety of disciplines attended a Conference on the Eradicability of Onchocerciasis at The Carter Center, in Atlanta GA, held January 22-24, 2002. The Conference, which was organized by The Carter Center and the World Health Organization, with funding from the Bill & Melinda Gates Foundation, addressed the question: "Is onchocerciasis (River Blindness) eradicable with current knowledge and tools?" Former US President Jimmy Carter attended part of the final plenary proceedings on January 24.The Conference consisted of a series of presentations by invited expert speakers (Appendix C) and further deliberations in four workgroups (Appendix D) followed by plenary discussion of major conclusions. The presentations underlined epidemiological and entomological differences between onchocerciasis in Africa and the Americas. Whilst onchocerciasis in Africa covers extensive areas and is associated with striking human and fly population migrations and remarkably efficient black fly vectors, in the Americas onchocerciasis is found in limited foci. Human and fly population migration are not major problems in the Americas, where most black fly species are inefficient, though some efficient black flies are also found there. Vector control has been effectively applied in the Onchocerciasis Control Program in West Africa (OCP) with remarkable results, interrupting transmission in most parts of the original Program area. The use of ivermectin has given variable results: while ivermectin treatment has been effective in all endemic areas in controlling onchocerciasis as a public health problem, its potential for interrupting transmission is more promising in hypo- and mesoendemic areas. The African Program for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, applies ivermectin, its principal control tool, to communities in high-risk areas as determined by rapid epidemiological mapping of onchocerciasis (REMO) and Geographic Information Systems (GIS). In the Americas, through support of the Onchocerciasis Elimination Program in the Americas (OEPA), a strategy of bi-annual ivermectin treatment of at least 85% of the eligible populations in all endemic communities is showing very good results and promises to be effective in eliminating onchocerciasis in the region.The Conference concluded that onchocerciasis is not eradicable using current tools due to the major barriers to eradication in Africa. However, the Conference also concluded that in most if not all the Americas, and possibly Yemen and some sites in Africa, transmission of onchocerciasis can be eliminated using current tools. The Conference recommended that where interruption of transmission is feasible and cost effective, programs should aim for that goal using all appropriate and available interventions so that the Onchocerca volvulus can eventually be eliminated and interventions halted. Although interruption of

2002年1月22日至24日,来自不同学科的64位专家参加了在佐治亚州亚特兰大卡特中心举行的关于盘尾丝虫病可根除性的会议。这次会议由卡特中心和世界卫生组织组织,由比尔和梅林达·盖茨基金会提供资金,讨论的问题是:“利用目前的知识和工具,盘尾丝虫病(河盲症)是否可以根除?”1月24日,美国前总统吉米·卡特出席了最后全体会议的部分会议。会议包括邀请专家发言者作一系列介绍(附录C)和四个工作组的进一步审议(附录D),然后是对主要结论的全体讨论。这些介绍强调了非洲和美洲盘尾丝虫病在流行病学和昆虫学方面的差异。虽然非洲的盘尾丝虫病覆盖了广泛的地区,并与惊人的人类和苍蝇种群迁徙以及非常有效的黑蝇媒介有关,但在美洲,盘尾丝虫病仅在有限的疫源地发现。在美洲,人类和苍蝇种群的迁徙并不是主要问题,尽管在那里也发现了一些高效的黑蝇,但大多数黑蝇物种都是低效的。病媒控制在西非盘尾丝虫病控制规划(OCP)中得到了有效应用,取得了显著效果,阻断了原规划区域大部分地区的传播。伊维菌素的使用产生了不同的结果:虽然伊维菌素治疗在所有流行地区控制盘尾丝虫病作为一个公共卫生问题是有效的,但它在低流行和中流行地区阻断传播的潜力更有希望。非洲盘尾丝虫病控制规划支持在OCP以外的非洲流行国家控制盘尾丝虫病,将其主要控制工具伊维菌素应用于盘尾丝虫病快速流行病学制图和地理信息系统确定的高危地区社区。在美洲,通过对美洲消除盘尾丝虫病规划(OEPA)的支持,一项对所有流行社区至少85%的符合条件人群进行两年一次伊维菌素治疗的战略显示出非常好的效果,有望有效消除该区域的盘尾丝虫病。会议的结论是,由于在非洲消灭盘尾丝虫病的主要障碍,利用现有工具无法根除盘尾丝虫病。然而,会议还得出结论,在大多数(如果不是全部)美洲,可能还有也门和非洲的一些地点,使用现有工具可以消除盘尾丝虫病的传播。会议建议,在阻断传播可行且具有成本效益的情况下,规划应利用所有适当和现有的干预措施,以实现这一目标,从而最终消除扭转盘尾丝虫病并停止干预措施。虽然目前在非洲大部分地区无法阻断盘尾丝虫病的传播,但会议建议通过过去25年的盘尾丝虫病控制规划,努力保护西非没有盘尾丝虫病传播的地区。在非洲剩余的高流行和中流行疫源地,继续每年分发伊维菌素将使盘尾丝虫病得到控制,使其不再成为公共卫生问题或制约经济发展的因素。
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引用次数: 183
Impact on the quality of life of lymphoedema patients following introduction of a hygiene and skin care regimen in a Guyanese community endemic for lymphatic filariasis: A preliminary clinical intervention study. 在圭亚那社区流行淋巴丝虫病引入卫生和皮肤护理方案后对淋巴水肿患者生活质量的影响:初步临床干预研究
Pub Date : 2003-01-24 DOI: 10.1186/1475-2883-2-1
T McPherson

BACKGROUND: Hygiene and skin care are effective and important interventions in the management of lymphoedema secondary to lymphatic filariasis. We analyzed the impact on the quality of life that education and introduction of a designated nurse had on lymphoedema patients in a community that was endemic for lymphatic filariasis. METHODS: Patients' life quality was assessed using a Dermatology Life Quality Index (DLQI) questionnaire. At the same time they received education on appropriate hygiene, skin care techniques and simple exercises that encourage lymph drainage. A designated nurse was provided with educational materials and treatments. The DLQI life quality measure was repeated one year later. RESULTS: The DLQI improved for all patients and reported acute attacks were reduced. A paired t-test showed the improvement in DLQI to be highly significant (P = < 0.0001). CONCLUSIONS: A nurse-led service combined with patient education in communities endemic for lymphatic filariasis is an effective intervention in improving the quality of life of patients with lymphoedema.

背景:卫生和皮肤护理是管理淋巴丝虫病继发淋巴水肿的有效和重要的干预措施。我们分析了在一个淋巴丝虫病流行的社区中,教育和引入指定护士对淋巴水肿患者生活质量的影响。方法:采用皮肤病生活质量指数(DLQI)问卷对患者的生活质量进行评估。与此同时,他们接受了适当的卫生教育,皮肤护理技巧和促进淋巴排出的简单练习。一名指定的护士提供了教育材料和治疗。一年后再次进行DLQI生活质量测量。结果:所有患者DLQI均有改善,急性发作减少。配对t检验显示DLQI的改善非常显著(P = < 0.0001)。结论:在社区淋巴丝虫病流行中,护士主导的服务结合患者教育是改善淋巴水肿患者生活质量的有效干预措施。
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引用次数: 61
Tolerability and efficacy of single dose albendazole, diethylcarbamazine citrate (DEC) or co-administration of albendazole with DEC in the clearance of Wuchereria bancrofti in asymptomatic microfilaraemic volunteers in Pondicherry, South India: a hospital-based study. 单剂量阿苯达唑、枸橼酸乙胺嗪(DEC)或阿苯达唑与枸橼酸乙胺嗪联合用药对南印度本迪榭里无症状微丝蚴病志愿者清除班克罗夫蒂虫的耐受性和疗效:一项基于医院的研究。
Pub Date : 2002-10-10 DOI: 10.1186/1475-2883-1-1
SP Pani, G Subramanyam Reddy, LK Das, P Vanamail, SL Hoti, J Ramesh, PK Das

BACKGROUND: The tolerability and efficacy of single dose albendazole (400 mg), diethylcarbamazine citrate (DEC) (6 mg/kg bodyweight) or co-administration of albendazole (400 mg) + DEC (6 mg/kg bodyweight) was studied in 54 asymptomatic Wuchereria bancrofti microfilaraemic volunteers in a double blind hospital-based clinical study. RESULTS: There was no significant difference in the overall incidence of adverse reactions between the three drug groups [42.1% (albendazole), 52.9% (DEC) and 61.1% (albendazole + DEC); P > 0.05]. The mean score of adverse reaction intensity did not differ significantly between the DEC and albendazole + DEC groups. However, the values in these two groups were significantly higher compared to that of albendazole alone [1.8 +/- 3.0 (albendazole) vs. 5.6 +/- 7.1 (DEC), 6.7 +/- 6.6 (albendazole + DEC); P < 0.05]. By day 360 post-therapy there was no significant difference between the three drug groups in relation to the clearance of microfilaria [26.3% (albendazole), 17.6% (DEC), 27.8% (albendazole + DEC)], reduction in geometric mean parasite density [94.7% (albendazole), 89.5% (DEC), 95.4% (albendazole + DEC)] or reduction in filarial antigenaemia [83% (albendazole), 87% (DEC), 75% (albendazole + DEC)]. Furthermore, there was a significant decrease in mean geometric parasite density (P < 0.05) as well as antigenaemia optical density values (P < 0.01) between pre-therapy levels and day 360 post-therapy in all three groups. CONCLUSIONS: This study has shown that single dose albendazole (400 mg) has similar efficacy in the clearance of microfilaria as that of DEC or the co-administration of the two drugs. The results strengthen the rationale of using albendazole for mass annual single dose administration for the control of transmission of lymphatic filariasis.

背景:在一项以医院为基础的双盲临床研究中,研究了54名无症状班克罗非虫微丝蚴感染志愿者服用单剂量阿苯达唑(400毫克)、枸橼酸乙胺嗪(DEC)(6毫克/千克体重)或同时服用阿苯达唑(400毫克)+DEC(6毫克/千克体重)的耐受性和疗效。结果:三组药物的不良反应总发生率无显著差异[42.1%(阿苯达唑)、52.9%(DEC)和 61.1%(阿苯达唑 + DEC);P > 0.05]。不良反应强度的平均值在 DEC 组和阿苯达唑+DEC 组之间没有显著差异。然而,这两组的不良反应值明显高于阿苯达唑单药组[1.8 +/- 3.0(阿苯达唑)vs 5.6 +/- 7.1(DEC),6.7 +/- 6.6(阿苯达唑 + DEC);P < 0.05]。到治疗后第 360 天,三组药物在清除微丝蚴方面没有显著差异[26.3%(阿苯达唑)、17.6%(DEC)、27.8%(阿苯达唑 + DEC)]、寄生虫几何平均密度降低[94.7%(阿苯达唑)、89.5%(DEC)、95.4%(阿苯达唑 + DEC)]或抗丝虫血症降低[83%(阿苯达唑)、87%(DEC)、75%(阿苯达唑 + DEC)]。此外,所有三组的平均几何寄生虫密度(P < 0.05)和抗虫血光密度值(P < 0.01)在治疗前水平和治疗后第 360 天之间都有显著下降。结论:本研究表明,单剂量阿苯达唑(400 毫克)清除微丝蚴的疗效与 DEC 或两种药物联合使用的疗效相似。研究结果加强了每年使用阿苯达唑单剂大规模控制淋巴丝虫病传播的合理性。
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引用次数: 0
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Filaria journal
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