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Drug resistance in Giardia: Mechanisms and alternative treatments for Giardiasis. 贾第虫的耐药性:贾第虫病的机制和替代治疗。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-01-17 DOI: 10.1016/bs.apar.2019.11.003
Raúl Argüello-García, David Leitsch, Tina Skinner-Adams, M Guadalupe Ortega-Pierres

The use of chemotherapeutic drugs is the main resource against clinical giardiasis due to the lack of approved vaccines. Resistance of G. duodenalis to the most used drugs to treat giardiasis, metronidazole and albendazole, is a clinical issue of growing concern and yet unknown impact, respectively. In the search of new drugs, the completion of the Giardia genome project and the use of biochemical, molecular and bioinformatics tools allowed the identification of ligands/inhibitors for about one tenth of ≈150 potential drug targets in this parasite. Further, the synthesis of second generation nitroimidazoles and benzimidazoles along with high-throughput technologies have allowed not only to define overall mechanisms of resistance to metronidazole but to screen libraries of repurposed drugs and new pharmacophores, thereby increasing the known arsenal of anti-giardial compounds to some hundreds, with most demonstrating activity against metronidazole or albendazole-resistant Giardia. In particular, cysteine-modifying agents which include omeprazole, disulfiram, allicin and auranofin outstand due to their pleiotropic activity based on the extensive repertoire of thiol-containing proteins and the microaerophilic metabolism of this parasite. Other promising agents derived from higher organisms including phytochemicals, lactoferrin and propolis as well as probiotic bacteria/fungi have also demonstrated significant potential for therapeutic and prophylactic purposes in giardiasis. In this context the present chapter offers a comprehensive review of the current knowledge, including commonly prescribed drugs, causes of therapeutic failures, drug resistance mechanisms, strategies for the discovery of new agents and alternative drug therapies.

由于缺乏经批准的疫苗,化疗药物的使用是对抗临床贾第虫病的主要资源。贾第鞭毛虫对甲硝唑和阿苯达唑这两种治疗贾第鞭毛虫病最常用的药物的耐药性分别是一个日益受到关注的临床问题,但影响尚不清楚。在寻找新药的过程中,贾第鞭毛虫基因组计划的完成以及生化、分子和生物信息学工具的使用,使这种寄生虫中约150个潜在药物靶点的十分之一的配体/抑制剂得以鉴定。此外,第二代硝基咪唑和苯并咪唑的合成以及高通量技术不仅可以确定甲硝唑耐药的总体机制,还可以筛选重新利用的药物和新药效团,从而将已知的抗贾第鞭虫化合物库增加到数百种,其中大多数显示出对甲硝唑或阿苯达唑耐药的贾第鞭虫具有活性。特别是,半胱氨酸修饰剂,包括奥美拉唑、双硫醚、大蒜素和金嘌呤,由于其基于广泛的含硫醇蛋白质和这种寄生虫的微嗜气代谢的多效性而突出。来自高等生物的其他有希望的药物,包括植物化学物质、乳铁蛋白和蜂胶,以及益生菌/真菌,也显示出治疗和预防贾第虫病的巨大潜力。在此背景下,本章提供了当前知识的全面回顾,包括常用处方药,治疗失败的原因,耐药机制,发现新药和替代药物治疗的策略。
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引用次数: 47
Preface. 前言。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 DOI: 10.1016/S0065-308X(20)30050-6
M Guadalupe Ortega-Pierres
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引用次数: 0
Series Page 系列页面
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 DOI: 10.1016/s0065-308x(20)30081-6
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引用次数: 0
Series Page 系列页面
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 DOI: 10.1016/s0065-308x(20)30100-7
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引用次数: 0
Toxocara prevalence in dogs, cats and the environment in Russia. 弓形虫在俄罗斯狗、猫和环境中的流行。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-04-09 DOI: 10.1016/bs.apar.2020.01.019
Alexander N Lukashev, Maria N Ruzina, Lyudmila V Akhmadishina

The toxocariasis incidence in Russia is relatively low (1.8 cases per 100,000 individuals) and the parasite is not a major healthcare concern. However, the proportion of primary hosts testing positive for the parasite is high and varies between 3% and 100% in dogs (on average 33%), and between 6% and 52% in cats. Higher prevalence was observed in Volga, Urals and Siberia regions. Levels of contamination of soil, children's playgrounds and sandboxes is also high, with up to 100% contamination rates determined in some studies, but more commonly prevalence of contamination around 40% was reported. There is a pronounced seasonality in the prevalence of Toxocara in primary hosts and the soil, with peaks in the summer and autumn. Most likely, a lack of permissive conditions for the development of eggs in the winter determines observed seasonal patterns, which are different than those observed in most other countries. Toxocara eggs were found in 4-10% of vegetables and greenery samples tested, suggesting that they can contribute to the transmission of Toxocara.

俄罗斯的弓形虫病发病率相对较低(每10万人中有1.8例),这种寄生虫不是主要的卫生保健问题。然而,原发宿主的寄生虫检测呈阳性的比例很高,在狗中为3%至100%(平均为33%),在猫中为6%至52%。伏尔加河、乌拉尔和西伯利亚地区的患病率较高。土壤、儿童游乐场和沙箱的污染水平也很高,一些研究确定的污染率高达100%,但更普遍的污染发生率约为40%。弓形虫在主要宿主和土壤中的流行有明显的季节性,夏季和秋季为高峰。最有可能的是,在冬季缺乏卵发育的有利条件决定了观察到的季节模式,这与大多数其他国家观察到的不同。在4-10%的蔬菜和绿色植物样本中发现了弓形虫卵,这表明它们可能有助于弓形虫的传播。
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引用次数: 2
Toxocara "omics" and the promises it holds for medicine and veterinary medicine. 弓形虫“组学”及其对医学和兽医学的承诺。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-04-01 DOI: 10.1016/bs.apar.2020.01.002
Wen-Bin Zheng, Yang Zou, Xing-Quan Zhu, Guo-Hua Liu

Toxocariasis is one of the most neglected worldwide zoonoses that is caused by larval nematode parasites of the genus Toxocara, Toxocara canis, and to a lesser extent, Toxocara cati, whose migration mechanism is still largely unknown. Fortunately, some advanced tools have been employed, such as genomics, transcriptomics, and proteomics, to better understand the molecular biology and regulatory mechanisms of Toxocara. Using genomics and transcriptomics, we can identify a large number of genes that participate in the development of Toxocara and the interaction of parasites and their hosts and can predict the functions of unknown genes by comparing them with other relevant species. Using proteomics, we can identify somatic proteins and excretory and secretory (ES) proteins that perform specific biological functions in tissue degradation, pathogen invasion, immune evasion or modulation. These "omics" techniques also can contribute enormously to the development of new drugs, vaccines and diagnostic tools for toxocariasis. In a word, by utilizing "omics", we can better understand the Toxocara and toxocariasis. In this review, we summarized the representative achievements in Toxocara and the interaction between Toxocara spp. and their hosts based on expressed sequence tags (ESTs), microarray gene expression, next-generation sequencing (NGS) technologies and liquid chromatography-tandem mass spectrometry (LC-MS/MS), hoping to better understand the molecular biology of Toxocara, and contribute to new progress in the application areas of new drugs, vaccines and diagnostic tool for toxocariasis in the future.

弓形虫病是世界范围内最被忽视的人畜共患病之一,它是由弓形虫属的幼虫线虫寄生虫,犬弓形虫和较小程度上的猫弓形虫引起的,其迁移机制在很大程度上仍然未知。幸运的是,一些先进的工具,如基因组学、转录组学和蛋白质组学,已经被用来更好地了解弓形虫的分子生物学和调节机制。利用基因组学和转录组学,我们可以鉴定出大量参与弓形虫发育和寄生虫与宿主相互作用的基因,并通过与其他相关物种的比较来预测未知基因的功能。利用蛋白质组学,我们可以鉴定在组织降解、病原体入侵、免疫逃避或调节中发挥特定生物学功能的体细胞蛋白和排泄和分泌(ES)蛋白。这些“组学”技术还可以极大地促进弓形虫病新药、疫苗和诊断工具的开发。总之,利用“组学”,我们可以更好地了解弓形虫和弓形虫病。本文基于表达序列标签(est)、微阵列基因表达、新一代测序(NGS)技术和液相色谱-串联质谱(LC-MS/MS)技术,综述了近年来在弓形虫及其与宿主相互作用方面的代表性研究成果,以期更好地了解弓形虫的分子生物学,并在新药应用领域取得新进展。未来弓形虫病的疫苗和诊断工具。
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引用次数: 18
Seroprevalence and incidence of human toxocarosis in Russia. 俄罗斯人类毒血症的血清患病率和发病率。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-04-09 DOI: 10.1016/bs.apar.2020.01.015
Lyudmila V Akhmadishina, Maria N Ruzina, Maria A Lukasheva, Karen K Kyuregyan, Mikhail I Mikhailov, Alexander N Lukashev

Overall incidence of toxocariasis in Russia is low and varies between 1.6 and 2.7 per 100,000, while in several hyper-endemic regions, such as Altay, Kurgan, Perm and Udmurtia, it reaches 43 per 100,000. The seroprevalence of toxocariasis in published references was on average 16% and varied across the regions of Russia from negligible in North Siberia to 40% in southern regions of West Siberia. Seroprevalence in adults in five regions of Russia identified in this study was on average 20%, and varied from 3% in Yakutia (north of East Siberia) to 36% in Rostov-on-Don, South Russia. There was no correlation between seroprevalence and reported incidence of toxocariasis; however, the pattern of seroprevalence variation could be linked to Toxocara prevalence in dogs. Toxocariasis seroprevalence has more than doubled over the last 20 years. Diagnostic antibody titres (1:800 or more) were found in 3.6% of sera, suggesting about five million of acute Toxocara invasions per year.

俄罗斯弓形虫病的总体发病率很低,介于每10万人1.6至2.7人之间,而在几个高流行地区,如阿勒泰、库尔干、彼尔姆和乌德穆尔特,发病率达到每10万人43人。在已发表的文献中,弓形虫病的血清患病率平均为16%,在俄罗斯各地有所不同,从北西伯利亚的可以忽略不计到西西伯利亚南部地区的40%。本研究确定的俄罗斯五个地区成人血清阳性率平均为20%,从雅库特(东西伯利亚北部)的3%到俄罗斯南部顿河畔罗斯托夫的36%不等。血清阳性率与报告的弓形虫病发病率之间无相关性;然而,血清阳性率变化的模式可能与犬中弓形虫的流行有关。弓形虫病血清患病率在过去20年中增加了一倍以上。在3.6%的血清中发现诊断性抗体滴度(1:800或更高),表明每年约有500万例急性弓形虫入侵。
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引用次数: 1
Toxocara: Seroprevalence in Mexico. 弓形虫:墨西哥的血清患病率。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-02-05 DOI: 10.1016/bs.apar.2020.01.012
Martha Ponce-Macotela, Mario Noé Martínez-Gordillo

In Mexico, toxocariasis, like some other parasitosis in humans, is not a disease of conventional surveillance or immediate notification. Seroprevalence studies are scarce, six dealing with paediatric populations and eight dealing with adults; the reports were only from four states in Mexico. There were 1596 children, and the seroprevalence was 13.8%. In the case of adults, there were 1827 subjects, and seroprevalence was 4.7%. There is a significant positive association between seroprevalence and the paediatric population P<0.0001 (OR, 3.285; 95% CI, 2.541-4.279). It is advisable to perform competitive ELISAs and add another diagnostic test, such as Western blot or the detection of circulating antigens to reduce diagnostic uncertainty. This neglected parasitosis can be confused with retinoblastoma. Therefore, there is a risk of ocular enucleation. It is necessary to sensitise the authorities of the Ministry of Health and decision-makers, to provide economic support for epidemiological surveillance of this zoonotic parasite.

在墨西哥,弓形虫病与其他一些人类寄生虫病一样,不是一种常规监测或立即通报的疾病。血清患病率研究很少,其中6项涉及儿科人群,8项涉及成人;这些报告仅来自墨西哥的四个州。患儿1596例,血清阳性率为13.8%。在成人病例中,共有1827名受试者,血清阳性率为4.7%。血清阳性率与儿科人群P呈显著正相关
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引用次数: 3
Elucidating the molecular and developmental biology of parasitic nematodes: Moving to a multiomics paradigm. 阐明寄生线虫的分子和发育生物学:转向多组学范式。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-01-31 DOI: 10.1016/bs.apar.2019.12.005
Guangxu Ma, Tao Wang, Pasi K Korhonen, Andreas Hofmann, Paul W Sternberg, Neil D Young, Robin B Gasser

In the past two decades, significant progress has been made in the sequencing, assembly, annotation and analyses of genomes and transcriptomes of parasitic worms of socioeconomic importance. This progress has somewhat improved our knowledge and understanding of these pathogens at the molecular level. However, compared with the free-living nematode Caenorhabditis elegans, the areas of functional genomics, transcriptomics, proteomics and metabolomics of parasitic nematodes are still in their infancy, and there are major gaps in our knowledge and understanding of the molecular biology of parasitic nematodes. The information on signalling molecules, molecular pathways and microRNAs (miRNAs) that are known to be involved in developmental processes in C. elegans and the availability of some molecular resources (draft genomes, transcriptomes and some proteomes) for selected parasitic nematodes provide a basis to start exploring the developmental biology of parasitic nematodes. Indeed, some studies have identified molecules and pathways that might associate with developmental processes in related, parasitic nematodes, such as Haemonchus contortus (barber's pole worm). However, detailed information is often scant and 'omics resources are limited, preventing a proper integration of 'omic data sets and comprehensive analyses. Moreover, little is known about the functional roles of pheromones, hormones, signalling pathways and post-transcriptional/post-translational regulations in the development of key parasitic nematodes throughout their entire life cycles. Although C. elegans is an excellent model to assist molecular studies of parasitic nematodes, its use is limited when it comes to explorations of processes that are specific to parasitism within host animals. A deep understanding of parasitic nematodes, such as H. contortus, requires substantially enhanced resources and the use of integrative 'omics approaches for analyses. The improved genome and well-established in vitro larval culture system for H. contortus provide unprecedented opportunities for comprehensive studies of the transcriptomes (mRNA and miRNA), proteomes (somatic, excretory/secretory and phosphorylated proteins) and lipidomes (e.g., polar and neutral lipids) of this nematode. Such resources should enable in-depth explorations of its developmental biology at a level, not previously possible. The main aims of this review are (i) to provide a background on the development of nematodes, with a particular emphasis on the molecular aspects involved in the dauer formation and exit in C. elegans; (ii) to critically appraise the current state of knowledge of the developmental biology of parasitic nematodes and identify key knowledge gaps; (iii) to cover salient aspects of H. contortus, with a focus on the recent advances in genomics, transcriptomics, proteomics and lipidomics as well as in vitro culturing systems; (iv) to review recent advances in our knowledge and understanding of the mol

在过去的二十年中,对具有社会经济意义的寄生虫基因组和转录组的测序、组装、注释和分析取得了重大进展。这一进展在一定程度上提高了我们对这些病原体在分子水平上的认识和理解。然而,与自由生活的秀丽隐杆线虫相比,寄生线虫的功能基因组学、转录组学、蛋白质组学和代谢组学等领域还处于起步阶段,我们对寄生线虫分子生物学的认识和理解还存在较大差距。线虫发育过程中已知的信号分子、分子通路和microrna (mirna)的信息以及部分寄生性线虫分子资源(基因组草图、转录组和部分蛋白质组)的可用性为寄生性线虫的发育生物学研究提供了基础。事实上,一些研究已经确定了一些分子和途径,这些分子和途径可能与相关的寄生线虫的发育过程有关,比如弯血线虫(理发师杆虫)。然而,详细的信息往往是缺乏的,组学资源是有限的,这阻碍了对组学数据集和全面分析的适当整合。此外,人们对信息素、激素、信号通路和转录后/翻译后调控在寄生性线虫整个生命周期中的功能作用知之甚少。虽然秀丽隐杆线虫是一个很好的模型,以协助寄生线虫的分子研究,它的使用是有限的,当涉及到寄生在宿主动物的特定过程的探索。要深入了解寄生线虫,如H. contortus,需要大量增加资源和使用综合组学方法进行分析。线虫基因组的改进和体外幼虫培养系统的完善为线虫转录组(mRNA和miRNA)、蛋白质组(体细胞、排泄/分泌和磷酸化蛋白)和脂质组(如极性脂质和中性脂质)的综合研究提供了前所未有的机会。这些资源应该能够在以前不可能的水平上对其发育生物学进行深入探索。这篇综述的主要目的是:(1)提供线虫发展的背景,特别强调在秀丽隐杆线虫的水形成和退出的分子方面;(ii)批判性地评估寄生线虫发育生物学知识的现状,并确定关键的知识空白;(iii)介绍弯齿莲的主要方面,重点介绍基因组学、转录组学、蛋白质组学和脂质组学以及体外培养系统的最新进展;(iv)回顾了利用综合多组学方法在线虫分子和发育生物学方面的最新进展,并讨论了该方法在详细探索与线虫发育、适应和寄生相关的信号分子、分子过程和途径以及识别针对这些病原体的新干预靶点方面的意义。显然,最近建立的多组学方法很容易适用于在分子水平上探索广泛的有趣的和具有社会经济意义的寄生虫(也包括吸虫和绦虫),并阐明宿主-寄生虫相互作用和疾病过程。
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引用次数: 19
Canine Toxocariosis: Its prevalence, incidence and occurrence in the Indian subcontinent. 犬弓形虫病:其流行,发病率和发生在印度次大陆。
3区 医学 Q1 Immunology and Microbiology Pub Date : 2020-01-01 Epub Date: 2020-02-10 DOI: 10.1016/bs.apar.2020.01.018
Manigandan Lejeune, V Gnani Charitha, C Mathivathani, V C Rayulu, Dwight D Bowman

Toxocariosis is an important neglected tropical helminth disease of zoonotic significance for which canids are the definitive hosts. Dogs are also considered the sentinel host for the occurrence of T. canis infections in humans. Therefore, understanding its prevalence in canine population is imperative for any effective disease control in humans. A comprehensive review of literature on the prevalence of T. canis in canids was lacking from the Indian subcontinent which necessitated our efforts to compile available data published on this topic. Data on prevalence, incidence and occurrence of this helminths in canids were presented in this review as tabular format for easy comprehension. Moreover, the data were categorized based on the region where the studies were conducted with an aim to understand the spatial distribution of this parasite in the subcontinent. Factors influencing the regional prevalence/occurrence of T. canis such as type of canids (stray or pet), age, sex, breed, season and the choice of analytical methods were also discussed. In addition, data on the prevalence of T. canis in environmental samples and in zoo canids were also compiled and presented. We anticipate such an exhaustive review of literature available mostly in the journals published from the subcontinent would become a point source of information necessary for prioritizing future surveillance efforts in this region and for making informed policy decision to control this zoonotic helminth infection.

弓形虫病是一种重要的被忽视的热带寄生虫病,具有人畜共患的意义,其中犬科动物是最终宿主。狗也被认为是人类犬类感染发生的哨兵宿主。因此,了解其在犬群中的流行情况对于有效控制人类疾病至关重要。由于缺乏关于印度次大陆犬科动物中犬绦虫流行的文献综述,因此我们需要努力汇编关于这一主题的现有数据。为了便于理解,本文以表格形式介绍了该蠕虫在犬科动物中的流行率、发病率和发生情况。此外,这些数据是根据进行研究的区域进行分类的,目的是了解这种寄生虫在次大陆的空间分布。讨论了犬类(流浪犬或宠物)类型、年龄、性别、品种、季节和分析方法选择等影响犬类流行/发生的因素。此外,还汇编和介绍了环境样本和动物园犬科动物中犬绦虫的流行情况。我们预计,对主要发表在南亚次大陆期刊上的现有文献进行如此详尽的审查,将成为确定该地区未来监测工作的优先次序和做出明智的政策决定以控制这种人畜共患蠕虫感染所必需的信息源。
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引用次数: 1
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Advances in Parasitology
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