Schistosoma

血吸虫
  • 文章类型: Journal Article
    背景:蠕虫感染,包括Opissorchisviverrini,钩虫,还有TrichurisTrichiura,在Khong区很普遍,Champasack省,南部老挝人民民主共和国(PDR)。梅孔血吸虫引起的血吸虫病在Khong地区的岛屿上引起了公众的关注。这项研究旨在评估生态健康/单一健康方法与大规模药物管理(MDA)相结合以减少这些蠕虫感染的影响。
    方法:我们在Khong区的两个特有岛屿(Donsom和Donkhone)上使用阶梯式楔形试验方法进行了社区干预,Champasack省,老挝,2012年4月至2013年3月。在每个学习村,随机选择30-40户。选定家庭的所有成员,在研究期间在家的人被邀请参加研究。进行了一项基线研究以评估蠕虫感染,对梅本吉血吸虫感染的知识态度和实践,露天排便的行为和家里厕所的可用性。基线(T0)后,在Donsom(干预)和Donkhone岛(控制)实施了生态健康/单一健康方法。2014年(T1)进行了评估,干预实施完成一年后,评估生态健康/单一健康方法对蠕虫感染的短期影响,并比较干预和控制岛屿。2015年晚些时候,在控制岛(Donkhone)实施了生态健康/单一健康方法。实施干预后,寄生虫学评估在2015年(T2)每年在人类中进行,2016年(T3)和2017年(T4),并在2017年(T4)的狗中评估干预对蠕虫感染的长期影响。频率用于描述蠕虫感染的患病率。Logistic回归用于关联KAP(知识,态度,以及实践和开放式排便行为)以及减少干预和控制岛之间的蠕虫感染。使用McNemar检验,干预前后患病率的降低是相关的。应用两个独立的样本t检验来比较对照岛和干预岛之间蠕虫感染的每克平均卵(EPG)。使用配对t检验分别比较两个岛的干预之前(基线)和之后(随访)的粪便样品的平均EPG。低于0.05的P值被认为具有统计学意义。
    结果:Eco-Health/One-Health方法与单独使用大量药物给药(对照岛)相比,将S.mekongi的患病率降低9.0%[比值比(OR)=0.49,P=0.003]。此外,该干预方案可显著减少O.viverrini感染20.3%(OR=1.92,P<0.001),减少钩虫17.9%(OR=0.71,P=0.045),分别。2012年至2017年的年度寄生虫学评估表明,生态健康/单一健康方法,再加上MDA,在干预岛上,梅孔吉的患病率从29.1%稳步下降到1.8%,在控制岛上从28.4%下降到3.1%,分别。
    结论:研究结果表明,生态健康/单一健康方法似乎与S.mekongi和蠕虫共感染的患病率显着降低有关,尤其是钩虫和T.trichiura.因此,在血吸虫病流行地区实施生态健康/单一健康方法可以加快实现到2025年阻断传播和到2030年消除传播的国家目标。
    BACKGROUND: Helminth infections, including Opisthorchis viverrini, hookworm, and Trichuris trichiura, are prevalent in Khong district, Champasack province, southern Lao People\'s Democratic Republic (PDR). Schistosomiasis caused by Schistosoma mekongi is of public health concern on the islands of the Khong district. This study aimed to assess the impact of an Eco-Health/One-Health approach in combination with mass drug administration (MDA) to reduce these helminth infections.
    METHODS: We conducted a community intervention using a stepped-wedge trial approach on two endemic islands (Donsom and Donkhone) of the Khong district, Champasack province, Lao PDR, between April 2012 and March 2013. In each study village, 30-40 households were randomly selected. All members of selected households, who were at home during the study period were invited to participate in the study. A baseline study was conducted to assess helminth infections, knowledge attitudes and practices toward Schistosoma mekongi infection, behavior of open defecation and availability of latrine at home. After the baseline (T0), the Eco-Health/One-Health approach was implemented on Donsom (intervention) and Donkhone island (control). An assessment was conducted in 2014 (T1), one year after the completion of intervention implementation, to assess the short-term impact of the Eco-Health/One-Health approach on helminth infections and compare intervention and control islands. Later in 2015, the Eco-Health/One-Health approach was implemented on control island (Donkhone). After the implementation of intervention, the parasitological assessments were conducted annually in humans in 2015 (T2), in 2016 (T3) and in 2017 (T4), and in dogs in 2017 (T4) to evaluate the long-term impact of the intervention on helminth infections. Frequency was used to describe the prevalence of helminth infections. Logistic regression was applied to associate the KAP (knowledge, attitudes, and practices and open defecation behavior) and the reduction of helminth infections between intervention and control islands. The reduction in prevalence pre- and post-intervention was associated using a McNemar test. A two-independent sample t-test was applied to compare the mean eggs per gram (EPG) of helminth infections between control and intervention islands. A paired t-test test was used to compare the mean EPG of stool samples before (baseline) and after (follow-up) interventions for the two islands separately. A P-value lower than 0.05 was considered statistically significant.
    RESULTS: Eco-Health/One-Health approach appears to be associated with reduction in prevalence of S. mekongi by 9.0% [odds ratio (OR) = 0.49, P = 0.003] compared to the use of mass drug administration alone (control island). Additionally, this intervention package significantly reduced O. viverrini infection by 20.3% (OR = 1.92, P < 0.001) and hookworm by 17.9% (OR = 0.71, P = 0.045), respectively. Annual parasitological assessments between 2012 and 2017 showed that the Eco-Health/One-Health approach, coupled with MDA, steadily reduced the prevalence of S. mekongi on the intervention island from 29.1% to 1.8% and on the control island from 28.4% to 3.1%, respectively.
    CONCLUSIONS: The study findings suggest that the Eco-Health/One-Health approach appears to be associated with a significant reduction in prevalence of S. mekongi and helminth co-infections, particularly hookworm and T. trichiura. Therefore, implementing the Eco-Health/One-Health approach in schistosomiasis-endemic areas could accelerate the achievement of national goals for transmission interruption by 2025 and elimination by 2030.
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  • 文章类型: Journal Article
    背景:物种杂交在寄生虫传播方面是一个真正的问题,血吸虫病的流行病学和发病率。更好地了解物种杂交对临床管理的影响非常重要。
    方法:对被确诊为泌尿生殖道血吸虫病的撒哈拉以南移民进行了一项前瞻性观察性研究。采用了量身定制的协议,包括血吸虫血清学,用吡喹酮治疗前进行血吸虫病的特定尿液LAMP检查和超声检查。在第3、6和12个月进行了预定的随访,以监测治疗反应,将血吸虫杂种的患者携带者与仅遗传纯形式的携带者进行比较。
    结果:共有31名来自西非的男性患者被纳入研究,平均年龄为26.5岁。12例(38.7%)的患者是血吸虫杂种的携带者。与仅感染血吸虫的患者相比,杂种携带者的血红蛋白水平较低(13.8g/dL[SD1.8]对14.8g/dL[SD1.4],p=0.04),血尿的频率更高(100%对52.6%,p=0.005),超声评分较高(2.64,SD2.20vs0.89,SD0.99;p=0.02)。然而,杂交体的存在并未导致治疗后临床和分析应答的差异.
    结论:血吸虫杂种的存在似乎导致感染个体发病率增加。然而,它似乎不会导致治疗后诊断测试或临床和分析反应的差异.
    BACKGROUND: Species hybridization represents a real concern in terms of parasite transmission, epidemiology and morbidity of schistosomiasis. It is greatly important to better understand the impact of species hybridization for the clinical management.
    METHODS: A prospective observational study was carried out in sub-Saharan migrants who were diagnosed with confirmed genitourinary schistosomiasis. A tailored protocol was applied, including Schistosoma serology, a specific urine LAMP tests for schistosomiasis and an ultrasound examination before treatment with praziquantel. A scheduled follow-up was performed at 3, 6 and 12 months to monitor treatment response, comparing patients carriers of Schistosoma hybrids with carriers of only genetically pure forms.
    RESULTS: A total of 31 male patients from West Africa were included in the study with a mean age of 26.5 years. Twelve (38.7 %) of the patients were carriers of Schistosoma hybrids. As compared with patients infected with S. haematobium alone, hybrid carriers had lower haemoglobin levels (13.8 g/dL [SD 1.8] vs 14.8 g/dL [SD 1.4], p = 0.04), a greater frequency of hematuria (100 % vs 52.6 %, p = 0.005), a higher ultrasound score (2.64, SD 2.20 vs 0.89, SD 0.99; p = 0.02). However, the presence of hybrids did not result in differences in clinical and analytical responses after treatment.
    CONCLUSIONS: The presence of Schistosoma hybrids seems to cause increased morbidity in infected individuals. However, it does not appear to result in differences in diagnostic tests or in clinical and analytical responses after treatment.
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  • 文章类型: Journal Article
    众所周知,二倍体目的吸虫是人类的严重病原体,以及农场和野生动物;血吸虫属(血吸虫科)的成员负责人类血吸虫病(血吸虫病),影响热带和亚热带国家的2亿多人,动物血吸虫对哺乳动物和鸟类的感染具有重要的兽医学意义。Diplostomida也富含寄生于其他主要脊椎动物类群的物种。“孢子虫”在鱼类中具有致病性,爬行动物中的“螺旋藻科”。所有这些吸虫都有两个宿主生命周期,无性繁殖的幼虫通常在软体动物中,偶尔在环节动物中,成年人通常生活在脊椎动物宿主的血管中。病理学通常与对被困在各种组织/器官中的卵的炎症反应有关。另一方面,Diplostomidae和Strigeidae的代表具有三个或四个宿主的生命周期,其中脊椎动物通常不仅用作确定宿主,而且还用作中间宿主或副宿主。病理学通常与宿主组织内的尾蚴和中尾蚴的迁移有关。这些吸虫感染对农场和野生动物的影响可能是显著的。
    Trematodes of the order Diplostomida are well known as serious pathogens of man, and both farm and wild animals; members of the genus Schistosoma (Schistosomatidae) are responsible for human schistosomosis (schistosomiasis) affecting more than 200 million people in tropical and subtropical countries, and infections of mammals and birds by animal schistosomes are of great veterinary importance. The order Diplostomida is also rich in species parasitizing other major taxa of vertebrates. The \"Aporocotylidae\" sensu lato are pathogenic in fish, \"Spirorchiidae\" sensu lato in reptiles. All these flukes have two-host life cycles, with asexually reproducing larvae usually in mollusks and occasionally in annelids, and adults usually live in the blood vessels of their vertebrate hosts. Pathology is frequently associated with inflammatory reactions to eggs trapped in various tissues/organs. On the other hand, the representatives of Diplostomidae and Strigeidae have three- or four-host life cycles in which vertebrates often serve not only as definitive but also as intermediate or paratenic hosts. Pathology is usually associated with migration of metacercariae and mesocercariae within the host tissues. The impact of these trematode infections on both farm and wild animals may be significant.
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  • 文章类型: Journal Article
    血吸虫病是世界上发病率的主要原因,全世界有近8亿人面临血吸虫病的风险;它是仅次于疟疾的主要传染病。全球范围内,据估计,该病影响了世界78个国家的2.5亿多人,每年约有28万至50万人死亡。感染人类的三大血吸虫是曼氏血吸虫,日本血吸虫,和S.Hematomium。本章涵盖了血吸虫病的广泛方面,包括寄生虫的基本生物学,流行病学,免疫病理学,治疗,control,疫苗,和基因组学/蛋白质组学。在这一章中,读者将了解这种疾病在死亡率和发病率方面的重大损失。介绍了血吸虫的各个生命阶段的描述,这将为那些不熟悉这种疾病和有经验的科学家提供信息。涉及急性和慢性疾病的临床和公共卫生方面,诊断,目前的治疗方案和替代药物,和血吸虫病控制计划。包括基因组学和蛋白质组学的简要概述,详细介绍了该领域的最新进展,这将有助于科学家研究血吸虫的分子生物学。读者将对血吸虫病的一般方面和当前的研究进展表示赞赏。
    Schistosomiasis is a major cause of morbidity in the world and almost 800 million people worldwide are at risk for schistosomiasis; it is second only to malaria as a major infectious disease. Globally, it is estimated that the disease affects more than 250 million people in 78 countries of the world and is responsible for some 280,000-500,000 deaths each year. The three major schistosomes infecting humans are Schistosoma mansoni, S. japonicum, and S. haematobium. This chapter covers a wide range of aspects of schistosomiasis, including basic biology of the parasites, epidemiology, immunopathology, treatment, control, vaccines, and genomics/proteomics. In this chapter, the reader will understand the significant toll this disease takes in terms of mortality and morbidity. A description of the various life stages of schistosomes is presented, which will be informative for both those unfamiliar with the disease and experienced scientists. Clinical and public health aspects are addressed that cover acute and chronic disease, diagnosis, current treatment regimens and alternative drugs, and schistosomiasis control programs. A brief overview of genomics and proteomics is included that details recent advances in the field that will help scientists investigate the molecular biology of schistosomes. The reader will take away an appreciation for general aspects of schistosomiasis and the current research advances.
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  • 文章类型: Journal Article
    背景:世界卫生组织(WHO)通过的消除被忽视的热带病的路线图旨在消除血吸虫病,作为公共卫生问题,到2030年。尽管撒哈拉以南非洲几个国家在减少血吸虫病发病率控制方面取得了进展,还有更多的事情需要做。使用具有可接受的灵敏度和特异性的准确诊断进行适当的监测对于评估所有针对血吸虫病的努力的成功至关重要。显微镜,尽管灵敏度低,仍然是诊断疾病的黄金标准方法。尽管已经做出了许多努力来开发基于循环寄生虫蛋白的新诊断方法,遗传标记,血吸虫卵形态,以及它们的顺磁性,没有一个足够强大,以取代显微镜。这篇综述重点介绍了在野外和临床环境中检测血吸虫病的常见诊断方法。重大挑战,并提供了新的和新颖的机会和诊断途径,这对于支持消除血吸虫病至关重要。
    方法:我们搜索了PubMed的相关和可靠的已发表文献,Scopus,谷歌学者,和Web的科学。搜索策略主要由子主题决定,因此使用了以下词语(schistosom*,诊断,Kato-Katz,抗体测试,循环抗原,POC-CCA,UCP-LF-CAA,分子诊断,核酸扩增试验,微流体,实验室-在磁盘上,实验室芯片,重组酶聚合酶扩增(RPA),LAMP,便携式音序器,纳米抗体测试,相同的多重复序列,诊断TPP,已确认,无提取),和布尔运算符AND和/OR用于优化搜索容量。由于血吸虫病的全球公共卫生性质,我们还搜索了可靠的文件,reports,和国际卫生组织发表的研究论文,世界卫生组织(世卫组织)和疾病控制和消除中心。
    BACKGROUND: The roadmap adopted by the World Health Organization (WHO) for eliminating neglected tropical diseases aims to eliminate schistosomiasis, as a public health concern, by 2030. While progress has been made towards reducing schistosomiasis morbidity control in several sub-Saharan African countries, there is still more that needs to be done. Proper surveillance using accurate diagnostics with acceptable sensitivity and specificity is essential for evaluating the success of all efforts against schistosomiasis. Microscopy, despite its low sensitivity, remains the gold standard approach for diagnosing the disease. Although many efforts have been made to develop new diagnostics based on circulating parasite proteins, genetic markers, schistosome egg morphology, and their paramagnetic properties, none has been robust enough to replace microscopy. This review highlights common diagnostic approaches for detecting schistosomiasis in field and clinical settings, major challenges, and provides new and novel opportunities and diagnosis pathways that will be critical in supporting elimination of schistosomiasis.
    METHODS: We searched for relevant and reliable published literature from PubMed, Scopus, google scholar, and Web of science. The search strategies were primarily determined by subtopic, and hence the following words were used (schistosom*, diagnosis, Kato-Katz, antibody test, circulating antigen, POC-CCA, UCP-LF-CAA, molecular diagnostics, nucleic acid amplification test, microfluidics, lab-on a disk, lab-on chip, recombinase polymerase amplification (RPA), LAMP, portable sequencer, nanobody test, identical multi-repeat sequences, diagnostic TPPs, REASSURED, extraction free), and Boolean operators AND and/OR were used to refine the searching capacity. Due to the global public health nature of schistosomiasis, we also searched for reliable documents, reports, and research papers published by international health organizations, World Health Organization (WHO), and Center for Disease control and Elimination.
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  • 文章类型: Journal Article
    血吸虫病,一种被忽视的热带病,影响人类和动物,是由血吸虫属的吸虫引起的。这种疾病是由几种影响尿道等器官的血吸虫引起的,肝脏,膀胱,肠子,皮肤和胆管。该疾病的生命周期涉及中间宿主(蜗牛)和哺乳动物宿主。它影响靠近中间宿主丰富的水体的人。该疾病在各个阶段的常见临床表现包括发烧,发冷,头痛,咳嗽,排尿困难,增生和肾积水。迄今为止,大多数控制策略都依赖于有效的诊断,关于媒介和寄生虫生物学的化疗和公共卫生教育。显微镜(Kato-Katz)被认为是检测寄生虫的黄金标准,而吡喹酮是大规模治疗该疾病的首选药物,因为尚未开发出疫苗。以往有关血吸虫病的综述大多集中在流行病学方面,生命周期,诊断,控制和治疗。因此,需要进行符合现代发展的全面审查。这里,我们扩展这个领域以涵盖历史观点,全球影响,症状和检测,生化和分子表征,基因治疗,目前的药物和疫苗状况。我们还讨论了将植物用作新型抗血吸虫剂的潜在和替代来源的前景。此外,我们强调先进的分子技术,成像和人工智能可能在未来的疾病检测和治疗中有用。总的来说,使用最先进的工具和技术正确检测血吸虫病,以及疫苗或新的抗血吸虫药物的开发可能有助于消除这种疾病。
    Schistosomiasis, one of the neglected tropical diseases which affects both humans and animals, is caused by trematode worms of the genus Schistosoma. The disease is caused by several species of Schistosoma which affect several organs such as urethra, liver, bladder, intestines, skin and bile ducts. The life cycle of the disease involves an intermediate host (snail) and a mammalian host. It affects people who are in close proximity to water bodies where the intermediate host is abundant. Common clinical manifestations of the disease at various stages include fever, chills, headache, cough, dysuria, hyperplasia and hydronephrosis. To date, most of the control strategies are dependent on effective diagnosis, chemotherapy and public health education on the biology of the vectors and parasites. Microscopy (Kato-Katz) is considered the golden standard for the detection of the parasite, while praziquantel is the drug of choice for the mass treatment of the disease since no vaccines have yet been developed. Most of the previous reviews on schistosomiasis have concentrated on epidemiology, life cycle, diagnosis, control and treatment. Thus, a comprehensive review that is in tune with modern developments is needed. Here, we extend this domain to cover historical perspectives, global impact, symptoms and detection, biochemical and molecular characterization, gene therapy, current drugs and vaccine status. We also discuss the prospects of using plants as potential and alternative sources of novel anti-schistosomal agents. Furthermore, we highlight advanced molecular techniques, imaging and artificial intelligence that may be useful in the future detection and treatment of the disease. Overall, the proper detection of schistosomiasis using state-of-the-art tools and techniques, as well as development of vaccines or new anti-schistosomal drugs may aid in the elimination of the disease.
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  • 文章类型: Journal Article
    当两个物种杂交时,这两个亲本基因组被汇集在一起,一些等位基因可能是第一次相互作用。迄今为止,第一代杂种中转录组变化的程度,随着他们的功能结果构成了一个重要的知识差距,尤其是在寄生虫物种中。在这里,我们探索了血吸虫寄生虫血吸虫和牛血吸虫的第一代杂交的分子和功能结果。通过转录组学方法,我们测量了亲本物种和杂种的基因表达。我们描述并量化了杂种中遇到的表达谱以及受影响的主要生物学过程。多达7,100个基因落入特定的杂种表达谱(介于亲本表达水平之间,过度表达,表达不足,或表达为父系之一)。根据亲本杂交的方向,这些基因中的大多数都不同(S.牛母亲和S.hematobium父亲或相反),并取决于性别。对于给定的性别和交叉方向,因此,绝大多数基因未分配给杂种表达谱:它们要么是差异表达的基因,但不是任何杂种表达谱的典型特征,要么在杂种和亲本系之间以及亲本系之间都没有差异表达。杂种中最普遍的基因表达谱是中间基因(24%的基因分配给杂种表达谱)。这些结果表明,血链球菌和牛链球菌之间的转录组相容性仍然相当高。我们还发现了可能与杂种优势相关的过度优势模型(与亲本系相比,杂种中的基因过度表达和表达不足)的支持。尤其是女性,生殖过程等过程,代谢和细胞相互作用以及信号通路确实受到影响。因此,我们的研究为血吸虫杂种的生物学提供了新的见解,并有证据支持相容性和杂种优势。
    When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap, especially in parasite species. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrids between the blood fluke parasites Schistosoma haematobium and S. bovis. Through a transcriptomic approach, we measured gene expression in both parental species and hybrids. We described and quantified expression profiles encountered in hybrids along with the main biological processes impacted. Up to 7,100 genes fell into a particular hybrid expression profile (intermediate between the parental expression levels, over-expressed, under-expressed, or expressed like one of the parental lines). Most of these genes were different depending on the direction of the parental cross (S. bovis mother and S. haematobium father or the reverse) and depending on the sex. For a given sex and cross direction, the vast majority of genes were hence unassigned to a hybrid expression profile: either they were differentially expressed genes but not typical of any hybrid expression profiles or they were not differentially expressed neither between hybrids and parental lines nor between parental lines. The most prevalent profile of gene expression in hybrids was the intermediate one (24% of investigated genes). These results suggest that transcriptomic compatibility between S. haematobium and S. bovis remains quite high. We also found support for an over-dominance model (over- and under-expressed genes in hybrids compared to parental lines) potentially associated with heterosis. In females in particular, processes such as reproductive processes, metabolism and cell interactions as well as signaling pathways were indeed affected. Our study hence provides new insight on the biology of Schistosoma hybrids with evidences supporting compatibility and heterosis.
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  • 文章类型: Journal Article
    Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies have been carried out to determine the role of animals in its transmission. In Mali, it has been over three decades since the last molecular study of animal schistosomes was carried out. It is now urgent to identify circulating strains of the parasite because of potential interactions with other schistosome species, which could complicate disease control. The aim of our work was to study the composition and genetic structure of schistosome populations collected from cattle. The prevalence of schistosome was 23.9%, with the prevalences of Schistosoma bovis (Sb) and S. curassoni (Sc) estimated at 12.6% and 9.8%, respectively. No hybrid strains or S. haematobium were found. The parasites displayed distinct geographical distribution with Sb dominant in Bamako (78.8% and 98% in Central Bamako Slaughterhouse and Sabalibougou Slaughterhouses, respectively) and Sc dominant in Kayes (95.3%). Of the 476 parasites with a complete genetic profile, 60.4% were pure Sc, and were mainly from Kayes. We identified two clusters at the site level (Fst of 0.057 and 0.042 for Sb and Sc, respectively). Cluster 1 was predominantly composed of pure Sb parasites and cluster 2 was mainly composed of pure Sc parasites, from Bamako and Kayes, respectively. Our study shows that cattle schistosomiasis remains endemic in Mali with S. bovis and S. curassoni. A robust genetic structure between the different schistosome populations was identified, which included two clusters based on the geographical distribution of the parasites.
    UNASSIGNED: Structure génétique des populations de Schistosoma bovis et S. curassoni collectées chez des bovins au Mali.
    UNASSIGNED: La schistosomiase revêt une grande importance médicale et vétérinaire. Malgré la situation critique de la schistosomiase en Afrique subsaharienne, peu d’études épidémiologiques moléculaires ont été réalisées pour déterminer le rôle des animaux dans sa transmission. Au Mali, cela fait plus de trois décennies que la dernière étude moléculaire des schistosomes animaux a été réalisée. Il est désormais urgent d’identifier les souches circulantes du parasite en raison des interactions potentielles avec d’autres espèces de schistosomes, ce qui pourrait compliquer la lutte contre la maladie. Le but de notre travail était d’étudier la composition et la structure génétique des populations de schistosomes collectées chez des bovins. La prévalence des schistosomes était de 23,9 %, celles de Schistosoma bovis (Sb) et de S. curassoni (Sc) étant respectivement estimées à 12,6 % et 9,8 %. Aucune souche hybride ni S. haematobium n’ont été trouvés. Les parasites présentaient une répartition géographique distincte avec Sb dominant à Bamako (respectivement 78,8 % et 98 % aux Abattoirs Centraux de Bamako et aux Abattoirs de Sabalibougou) et Sc dominant à Kayes (95,3 %). Sur les 476 parasites ayant un profil génétique complet, 60,4 % étaient des Sc purs, et provenaient principalement de Kayes. Nous avons identifié deux clusters au niveau du site (Fst de 0,057 et 0,042 pour Sb et Sc, respectivement). Le groupe 1 était principalement composé de parasites Sb purs et le groupe 2 était principalement composé de parasites Sc purs, provenant respectivement de Bamako et de Kayes. Notre étude montre que la schistosomiase bovine reste endémique au Mali, avec S. bovis and S. curassoni. Une structure génétique robuste entre les différentes populations de schistosomes a été identifiée, comprenant deux groupes basés sur la répartition géographique des parasites.
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  • 文章类型: Journal Article
    抗药性寄生虫的扩展引起了对几种被忽视的寄生虫病的严重关注。我们最近在癌症方面的研究结果使我们设想使用肽-烷氧基胺作为一种高度选择性和有效的新药来对抗血吸虫成虫,血吸虫病的病原体。的确,杂合化合物的肽标签可以被蠕虫的消化酶水解,以提供高度不稳定的烷氧基胺,该烷氧基胺自发地和瞬时地均溶成自由基,然后用作抗血吸虫成虫寄生虫的药物。这种方法很好地总结为用叉子挖坟墓。制备了几种杂合肽-烷氧基胺,并清楚地显示出活性:两种测试化合物以100μg/mL的浓度在两小时内杀死50%的寄生虫。重要的是,不能产生烷基自由基的肽和烷氧基胺片段显示无活性。这一强有力的证据证实了所提出的机制:寄生虫蛋白酶对前药的特异性激活通过原位烷基自由基产生导致寄生虫死亡。
    The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents of schistosomiasis. Indeed, the peptide tag of the hybrid compounds can be hydrolyzed by worm\'s digestive enzymes to afford a highly labile alkoxyamine which homolyzes spontaneously and instantaneously into radicals-which are then used as a drug against Schistosome adult parasites. This approach is nicely summarized as digging their graves with their forks. Several hybrid peptide-alkoxyamines were prepared and clearly showed an activity: two of the tested compounds kill 50% of the parasites in two hours at a concentration of 100 µg/mL. Importantly, the peptide and alkoxyamine fragments that are unable to generate alkyl radicals display no activity. This strong evidence validates the proposed mechanism: a specific activation of the prodrugs by the parasite proteases leading to parasite death through in situ alkyl radical generation.
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  • 文章类型: Journal Article
    Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.
    [摘要] 血吸虫病是一种被忽视的人兽共患寄生虫病。目前, 吡喹酮是治疗血吸虫病的首选药物, 也是治疗日本血吸虫 病的唯一有效药物。自 20 世纪 70 年代问世以来, 吡喹酮已在大规模血吸虫病化疗中应用了 40 余年, 长期大规模使用导 致部分地区血吸虫对其产生了抗性, 因此迫切需要研发新型抗血吸虫药物作为候选替代药物。近期研究表明, 组蛋白去 乙酰化酶和组蛋白乙酰转移酶在血吸虫的生长发育以及繁殖等阶段中均起关键作用, 被认为是治疗血吸虫病的潜在药 物靶点。本文总结了组蛋白去乙酰化酶抑制剂与组蛋白乙酰转移酶抑制剂在抗血吸虫药物研究中的最新进展, 以期为 抗血吸虫新药的研发提供参考。.
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