Protozoan Infections

原生动物感染
  • 文章类型: Journal Article
    原生动物寄生虫是危害人类健康的主要生物,社会,和经济,尤其是在全球赤道地区。寄生虫病,包括利什曼病,疟疾,和其他人,有助于大多数发病率和死亡率。每年约有110万人死于这些疾病。缺乏许可的疫苗接种使这些疾病的全球影响恶化,强调安全有效药物对预防和治疗的重要性。然而,寄生虫耐药性的出现持续影响药物的可用性。对新药的需求推动了全球抗寄生虫药物发现研究,需要实施许多创新方法来维持有前途的分子的连续供应。药物再利用已经成为药物开发的一个引人注目的工具,为标准的从头方法提供具有成本效益和效率的替代方案。对药物重新定位候选药物的彻底检查显示,某些药物可能不会从其原始适应症中获益。尽管如此,它们可能在其他疾病中表现出更明显的效果。此外,某些药物可以产生协同作用,一起给药时可提高治疗效果。在这一章中,我们概述了药物再利用(有时称为药物再定位)中采用的方法,提出新的策略来克服这些障碍,并充分利用药物再利用的前景。我们重点介绍了几种主要的人类原生动物疾病和一系列用于各种原生动物感染的示例性药物,为每种疾病提供出色的结果。
    Protozoan parasites are major hazards to human health, society, and the economy, especially in equatorial regions of the globe. Parasitic diseases, including leishmaniasis, malaria, and others, contribute towards majority of morbidity and mortality. Around 1.1 million people die from these diseases annually. The lack of licensed vaccinations worsens the worldwide impact of these diseases, highlighting the importance of safe and effective medications for their prevention and treatment. However, the appearance of drug resistance in parasites continuously affects the availability of medications. The demand for novel drugs motivates global antiparasitic drug discovery research, necessitating the implementation of many innovative ways to maintain a continuous supply of promising molecules. Drug repurposing has come out as a compelling tool for drug development, offering a cost-effective and efficient alternative to standard de novo approaches. A thorough examination of drug repositioning candidates revealed that certain drugs may not benefit significantly from their original indications. Still, they may exhibit more pronounced effects in other disorders. Furthermore, certain medications can produce a synergistic effect, resulting in enhanced therapeutic effectiveness when given together. In this chapter, we outline the approaches employed in drug repurposing (sometimes referred to as drug repositioning), propose novel strategies to overcome these hurdles and fully exploit the promise of drug repurposing. We highlight a few major human protozoan diseases and a range of exemplary drugs repurposed for various protozoan infections, providing excellent outcomes for each disease.
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  • 文章类型: Journal Article
    结论:一组基因在受Spongospora皮下感染挑战的马铃薯的转录组学分析中,在抗性品种中上调而在易感品种中下调,在蛋白质水平没有显示相同的表达模式。
    CONCLUSIONS: A group of genes that were upregulated in a resistant cultivar while downregulated in a susceptible cultivar in a transcriptomics analysis of potato challenged by Spongospora subterranea infection, did not show the same expression pattern at the protein level.
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  • 文章类型: Journal Article
    原生动物在全球范围内的严重威胁日益引起人类的关注,动物,并且需要改进新的治疗策略以有效地治疗或减轻相关疾病的影响。欧米茄多不饱和脂肪酸(ω-PUFA),包括ω-3(ω-3)和ω-6(ω-6),是来自各种天然来源的成分,由于其在寄生虫感染中的治疗作用以及动物和人类的各种基本结构和调节功能而获得了极大的关注。ω-3和ω-6均通过代谢抗炎介质降低寄生虫的生长和存活率。如脂蛋白,resolvins,和保护剂,并对各种原生动物感染具有体内和体外保护作用。ω-PUFA已被证明通过一种公知的机制来调节宿主的免疫应答,例如(抑制花生四烯酸(AA)代谢过程,抗炎介质的产生,细胞内脂质的修饰,和核受体的激活),通过调节前列腺素等炎症,促进对寄生虫入侵者的更有效的免疫防御转变,白三烯,血栓烷,参与控制炎症反应。免疫调节可能涉及减少炎症,增强吞噬作用,并抑制寄生虫的毒力因子。ω-PUFA的独特特性可以预防原生动物感染,代表了一个重要的研究领域。这篇综述探讨了ω-PUFA对一些原生动物感染的临床影响。阐明预防人类和动物各种寄生虫感染的可能作用机制和支持疗法,比如弓形虫病,疟疾,球虫病,和查加斯病。ω-PUFA由于其直接的抗寄生虫作用和其调节宿主免疫应答的能力而显示出有望作为寄生虫感染的治疗方法。此外,我们讨论了当前的治疗方案,并对未来的研究提出了展望.这可能为这些复杂的全球健康问题提供替代或补充治疗选择。
    Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.
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  • 文章类型: Journal Article
    儿童急性腹泻是撒哈拉以南非洲国家儿童发病和死亡的主要原因之一。溶组织内阿米巴和蓝氏贾第虫是该地区儿童腹泻的常见原因。然而,在撒哈拉以南非洲国家,关于原生动物引起腹泻的研究很少。本研究旨在调查埃塞俄比亚一家公立医院5岁以下腹泻儿童中溶组织大肠埃希菌和兰氏杆菌的相对患病率并探讨其危险因素。在HiwotFana医院的腹泻儿童中进行了一项回顾性研究,埃塞俄比亚。包括从2020年9月1日至2022年12月31日在医院寻求治疗的所有5岁以下腹泻儿童的记录。使用结构化数据收集格式从1257名儿童的医疗记录中收集数据。将数据输入到Excel表格中,并导出到SPSS版本22中进行数据处理和分析。描述性统计检验,卡方,和逻辑区域分析用于确定原生动物感染的预测因子。在1257个案例中,962(76.5%)患有水样腹泻,其余239(19.0%)患有痢疾。腹泻儿童中溶组织菌和兰氏杆菌的合并患病率为11.8%(95%CI:9.6-13.4)。随着孩子年龄的增长,与其他原因的儿童相比,这两种原生动物感染的频率显着增加。在夏季有更多的腹泻病例,包括与溶组织肠球菌和兰氏杆菌相关的腹泻病例。这项研究表明,研究区域中幼儿diarhhea的10个原因中有1个可能是由溶组织大肠杆菌和G.lamblia引起的。这些发现呼吁以社区为基础的安全水和食品安全干预措施,以减少资源贫乏地区由原生动物感染引起的儿童腹泻。
    Acute childhood diarrhea is one of the leading causes of childhood morbidity and mortality in sub-Saharan African countries. Entamoeba histolytica and Giardia lamblia are the common cause of childhood diarrhea in the region. However, there are only few studies on protozoa causing diarrhea in sub-Saharan African countries. This study was conducted to investigate the relative prevalence and explore risk factors of E. histolytica and G. lamblia among diarrheic children of under 5 years in a public hospital of Ethiopia. A retrospective study was conducted among diarrheic children at Hiwot Fana hospital, Ethiopia. Records of all diarrheic children less than 5 years who had sought medical treatment in the hospital from September 1, 2020 to December 31, 2022 were included. Data were collected from 1257 medical records of the children using a structured data-collection format. Data were entered into an Excel sheet and exported into SPSS version 22 for data processing and analysis. Descriptive statistical tests, Chi-square, and logistic region analysis were applied to determine predictors of protozoa infections. Of the 1257 cases, 962 (76.5%) had watery diarrhea and the remaining 239 (19.0%) had dysentery. The combined prevalence of E. histolytica and G. lamblia among diarrheic children was 11.8% (95% CI: 9.6-13.4). As the age of children increased, the frequency of these two protozoan infections was significantly increased compared to children with other causes. There were more diarrhea cases during the summer season including those associated with E. histolytica and G. lamblia. This study revealed that 1 in 10 causes of diarhhea among young children in the study area was likely caused by E. histolytica and G. lamblia. These findings call for community-based safe water and food safety interventions in order to reduce childhood diarrhea caused by protozoan infections in resource-poor settings.
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  • 文章类型: Journal Article
    尽管在预防和治疗传染病方面取得了巨大进展,迄今为止,只有很少的抗寄生虫药物被开发出来。原生动物感染,如疟疾,利什曼病,锥虫病继续对全世界的公共卫生造成巨大的损失,强调需要发现新的抗原生动物药物。最近,对槲皮素的抗原生动物特性的研究激增,人类饮食中最丰富的类黄酮之一。在这次审查中,我们试图巩固目前关于槲皮素抗原生动物作用的知识,并为未来的研究提供最有成效的途径。槲皮素对诸如利什曼原虫的广谱病原体具有有效的抗原生动物活性。,锥虫属。,疟原虫。,隐孢子虫。,毛滴虫。,和弓形虫.除了其免疫调节作用,槲皮素破坏线粒体功能,诱导凋亡/坏死细胞死亡,削弱铁的吸收,抑制参与脂肪酸合成和糖酵解途径的多种酶,抑制DNA拓扑异构酶的活性,并下调这些病原体中各种热休克蛋白的表达。体内研究还表明槲皮素能有效降低寄生负荷,组织病理学损伤,和动物的死亡率。未来的研究应集中在设计有效的药物递送系统以提高槲皮素的口服生物利用度。将槲皮素掺入各种纳米载体系统将是管理局部皮肤感染的有希望的方法。然而,需要临床试验来验证槲皮素治疗各种原生动物感染的疗效.
    Despite tremendous advances in the prevention and treatment of infectious diseases, only few antiparasitic drugs have been developed to date. Protozoan infections such as malaria, leishmaniasis, and trypanosomiasis continue to exact an enormous toll on public health worldwide, underscoring the need to discover novel antiprotozoan drugs. Recently, there has been an explosion of research into the antiprotozoan properties of quercetin, one of the most abundant flavonoids in the human diet. In this review, we tried to consolidate the current knowledge on the antiprotozoal effects of quercetin and to provide the most fruitful avenues for future research. Quercetin exerts potent antiprotozoan activity against a broad spectrum of pathogens such as Leishmania spp., Trypanosoma spp., Plasmodium spp., Cryptosporidium spp., Trichomonas spp., and Toxoplasma gondii. In addition to its immunomodulatory roles, quercetin disrupts mitochondrial function, induces apoptotic/necrotic cell death, impairs iron uptake, inhibits multiple enzymes involved in fatty acid synthesis and the glycolytic pathways, suppresses the activity of DNA topoisomerases, and downregulates the expression of various heat shock proteins in these pathogens. In vivo studies also show that quercetin is effective in reducing parasitic loads, histopathological damage, and mortality in animals. Future research should focus on designing effective drug delivery systems to increase the oral bioavailability of quercetin. Incorporating quercetin into various nanocarrier systems would be a promising approach to manage localized cutaneous infections. Nevertheless, clinical trials are needed to validate the efficacy of quercetin in treating various protozoan infections.
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  • 文章类型: Case Reports
    在这个案例报告中,我们解决了1例最初被怀疑出现长期COVID症状的患者中出现的严重的枯落虫感染的诊断难题和临床意义.我们描述病人的病史,最初的症状,诊断测试,和治疗。一位60多岁的糖尿病女性患者出现严重的呼吸急促,最初被诊断为糖尿病酮症酸中毒(DKA)。DKA症状缓解后,持续的呼吸问题导致了COVID-19测试,这是负面的。胸部计算机断层扫描显示异常,提示支气管镜检查和支气管肺泡灌洗液分析,这证实了L.blattarum的存在。值得注意的是,即使在环境温度下进行4天的运输,原生动物仍然可以移动和存活。该病例强调了在有呼吸道症状的患者中考虑替代诊断和提高对布拉坦乳杆菌感染的认识的重要性。及时准确的管理。
    In this case report, we address the diagnostic challenges and clinical implications of severe infection with Lophomonas blattarum in a patient initially suspected of experiencing long COVID symptoms. We describe the patient\'s medical history, initial symptoms, diagnostic tests, and treatment. A female patient with diabetes in her early 60s presented with severe shortness of breath and was initially diagnosed with diabetic ketoacidosis (DKA). After resolution of her DKA symptoms, persistent respiratory issues led to a COVID-19 test, which was negative. A chest computed tomography scan revealed abnormalities, prompting bronchoscopy and bronchoalveolar lavage fluid analysis, which confirmed the presence of L. blattarum. Notably, the protozoan remained mobile and viable even after a 4-day transport at ambient temperature. This case emphasizes the importance of considering alternative diagnoses and improving awareness about L. blattarum infection in patients with respiratory symptoms, for timely and accurate management.
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  • 文章类型: Journal Article
    Histomoniasis is a deadly disease of turkeys causing devastating economic losses to the poultry industry. In field outbreaks, a presumptive diagnosis is made based on gross pathology lesions and confirmed by histopathology. An early detection tool with quick turnaround time is needed to prevent the spread of histomoniasis. With this objective, two studies were conducted in turkeys. In Study 1, 40 poults were housed in two pens (20 poults/pen) and challenged at 14 days of age with Histomonas meleagridis by intracloacal route. Blood samples were collected 4 days postchallenge. Fifty-five percent (22/40) of the blood samples tested positive for H. meleagridis based on PCR using primers targeted against the 18S rRNA gene and confirmed by sequencing. In Study 2, 40 poults were housed in two groups and raised in floor pens. Groups 1 and 2 served as negative and challenge controls, respectively. At 14 days of age, the birds in Group 2 were challenged with H. meleagridis by intracloacal route. Blood samples were collected 2 days postchallenge. Five percent (1/20) of the blood samples tested positive for H. meleagridis, based on PCR and confirmed by sequencing. The results from both studies indicate that H. meleagridis DNA can be detected in the blood samples by PCR and confirmed by sequencing as early as 4 days postchallenge. This early detection method could be applied in field outbreaks to detect and confirm histomoniasis as early as possible.
    Detección temprana de histomoniasis en muestras de sangre mediante PCR y secuenciación La histomoniasis es una enfermedad mortal de los pavos que causa pérdidas económicas devastadoras a la industria avícola. En los brotes de campo, se realiza un diagnóstico presuntivo basado en lesiones patológicas macroscópicas y se confirma mediante histopatología. Se necesita una herramienta de detección temprana con un tiempo de respuesta rápido para prevenir la propagación de la histomoniasis. Con este objetivo, se realizaron dos estudios en pavos. En el Estudio 1, se alojaron 40 pavipollos en dos corrales (20 pavipollos/corral) y se desafiaron a los 14 días de edad con Histomonas meleagridis por vía intracloacal. Se recolectaron muestras de sangre a los cuatro días después del desafío. El cincuenta y cinco por ciento (22/40) de las muestras de sangre resultaron positivas para H. meleagridis según el método de PCR utilizando iniciadores dirigidos contra el gene 18S rRNA y confirmado mediante secuenciación. En el Estudio 2, se alojaron 40 pavipollos en dos grupos y se criaron en corrales en piso. Los grupos 1 y 2 sirvieron como controles negativos y de desafío, respectivamente. A los 14 días de edad, las aves del Grupo 2 fueron expuestas a H. meleagridis por vía intracloacal. Se recolectaron muestras de sangre dos días después del desafío. El cinco por ciento (1/20) de las muestras de sangre dieron positivo para H. meleagridis, según el método de PCR y confirmado mediante secuenciación. Los resultados de ambos estudios indican que el ADN de H. meleagridis puede detectarse en las muestras de sangre mediante PCR y confirmarse mediante secuenciación tan pronto como cuatro días después de la exposición. Este método de detección temprana podría aplicarse en brotes de campo para detectar y confirmar la histomoniasis lo antes posible.
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  • 文章类型: Journal Article
    尽管付出了巨大的努力,肠道原生动物感染仍然是全球范围内重大的医疗保健问题。尽管许多即时(POC)测试正被越来越多地使用,粪便标本的显微镜检查仍然是诊断的主要手段,尤其是在资源有限的环境中。我们在印度北部农村地区的患者中评估了基于免疫层析的快速POC测试的实用性。总共78名患者被纳入研究。在显微镜下测试十二指肠贾第虫阳性的9个标本中,免疫层析测试(ICT)只能检测到5种(55.55%)。在显微镜下的两个标本中证明了溶组织内阿米巴/dispar,两者都被ICT错过了。其整体灵敏度,特异性,阳性和阴性预测值为50%,98.5%,83.3%,93%,分别。其性能被认为不令人满意。尽管基于ICT的测试提供了相对快速且劳动密集程度较低的替代方案,它们应用于补充而不是代替粪便显微镜检查。
    Despite great efforts, intestinal protozoan infections remain a significant healthcare concern worldwide. Although many point-of-care (POC) tests are increasingly being used, microscopic examination of stool specimens remains the mainstay for their diagnosis, especially in resource-limited settings. We assessed the utility of rapid POC tests based on immunochromatography among patients from rural Northern India. A total of 78 patients were enrolled in the study. Out of nine specimens that tested positive for Giardia duodenalis on microscopy, an immunochromatographic test (ICT) could detect only five (55.55%). Entamoeba histolytica/dispar was demonstrated in two specimens on microscopy, both of which were missed by ICT. Its overall sensitivity, specificity, and positive and negative predictive value were 50%, 98.5%, 83.3%, and 93%, respectively. Its performance was considered unsatisfactory. Although ICT-based tests provide a relatively rapid and less labor-intensive alternative, they should be used to supplement and not replace stool microscopy.
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  • 文章类型: Biography
    CharlesLouisAlphonseLaveran-1845年6月18日-1922年5月18日:法国第一个诺贝尔医学奖,“以表彰他对原生动物在引起疾病中所起作用的工作。”他死后一百年,他的工作和生活只剩下书面记录。这段时期的证人已经不存在了。AlphonseLaveran已成为历史的“对象”。他深陷动荡的历史时期,以政权更迭(君主制/帝国/共和国)危机为标志,军事事件(1830年法国在北非的殖民扩张,1870年和1914-1918年的战争)及其后果(殖民帝国和武装冲突期间感染的医疗影响,Dreyfus事件,除其他外),巴斯德“微生物学”的出现以及传染病传播的原因和模式的破译。一个处于军事和民用世界边缘的玩家,用自己的,有时不相容,要追求的目标和目标的愿景,AlphonseLaveran在一个处于变革阵痛的社会中经历了这些动荡,在他的家庭和科学环境中。矛盾的是,在21世纪,我们学习这位科学家和人类的主要来源既丰富又“稀缺”。他的科学出版物和他在各个学院的许多演讲,委员会和会议大部分是公开的和可访问的,给我们一个科学和医学研究专业人士的愿景,向人们展示和说服他的思想以及理论和实践见解。他同时代的著作,公共和私人,照亮-扭曲?-这个人有很多方面。另一方面,关于这个人和他的生活愿景,他的生活和他的家人和朋友。我们将依靠已经保存的档案,特别是在他的军事和平民生涯中欢迎他的组织,以及他的妻子MarieLaveran和他的同事MariePhisalix,法国最早的医学博士之一和著名的爬虫学家。这两个女性人物保存并为他的记忆做出了贡献。让我们仔细看看科学家背后的人,我们可以想象他通过留下的痕迹。
    Charles Louis Alphonse Laveran - 18 June 1845 - 18 May 1922: first French Nobel Prize in Medicine, \"in recognition of his work on the role played by protozoa in causing diseases\". One hundred years after his death, only written records remain of his work and life. The witnesses to this period are no more. Alphonse Laveran has become an \"object\" of history.He was deeply involved in a turbulent historical period, marked by crises of regime change (Monarchy/Empire/Republic), military events (French colonial expansion in North Africa from 1830, the wars of 1870 and 1914-1918) and their consequences (the medical impact of infections in the colonial empire and during armed conflicts, the Dreyfus affair, among others), the advent of Pasteurian \"microbiology\" and the deciphering of the causes and modes of transmission of infectious diseases. A player on the edge of the military and civilian worlds, with their own, sometimes incompatible, visions of the aims and objectives to be pursued, Alphonse Laveran lived through these upheavals in a society in the throes of change, in his family and scientific environment.Paradoxically, the primary sources available to us for learning about this scientist and man are both abundant and \"scarce\" for us in the 21st century. His scientific publications and many of his speeches at various academies, committees and meetings are for the most part public and accessible, giving us a vision of a professional in scientific and medical research in action, presenting and convincing people of his ideas and theoretical and practical insights. The writings of his contemporaries, both public and private, shed light on - distort? - the man\'s many facets. On the other hand, there are few surviving sources on the man and his vision of life, his life and that of his family and friends.We will rely on the archives that have been preserved, in particular by the organisations that welcomed him during his military and civilian career, as well as by his wife Marie Laveran and his colleague Marie Phisalix, one of the first doctors of medicine in France and a renowned herpetologist. These two female figures have preserved and contributed to his memory. Let\'s take a closer look at the man behind the scientist, as we can imagine him through the traces that remain.
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  • 文章类型: Journal Article
    在以国际旅行增加为特征的快速发展的全球格局中,迁移,和生态变化,这项研究揭示了欧洲针对中枢神经系统(CNS)的原生动物和蠕虫感染的出现。尽管传统上与热带地区有关,这些感染在非流行地区逐渐变得更加普遍。通过审查固有风险,潜在的结果,以及随之而来的挑战,这项研究强调了诊断局限性之间复杂的相互作用,特定人群亚群的易感性,以及气候波动的深远影响。当代社会的相互联系是引入和建立这些感染的渠道,值得全面评估。这项研究强调了提高临床医生警惕性的关键作用,明智的公共卫生干预措施,和协同研究合作,以减轻这些感染的潜在后果。虽然罕见,它们对发病率和死亡率的深远影响强调了保护欧洲民众神经系统健康所需的集体紧迫性。通过这种多方面的方法,欧洲可以有效地驾驭这些紧急感染造成的复杂地形。
    In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for introducing and establishing these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed with these emergent infections.
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