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Ecological determinants and indicator-based analysis of Aedes albopictus expansion in a Central European metropolis: implications for urban sustainability 中欧大都市白纹伊蚊扩张的生态决定因素和指标分析:对城市可持续性的影响。
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.actatropica.2025.107937
Attila J Trájer
The invasive bridge vector mosquito Aedes albopictus has been increasingly detected across Europe, posing potential risks for arboviral disease transmission. Urban-scale assessments of its expansion remain scarce in Central Europe. The establishment and spread of Ae. albopictus in Budapest were analysed between 2018 and 2025 using spatio-temporal mapping, seasonal observations, and indicator-based ecological modelling, complemented by ensemble machine learning approaches. Occurrence patterns followed a logistic growth trajectory (R² = 0.995), with colonization rising from sparse foci in 2020 to over 85% of districts by 2025. Seasonal activity extended from late April to mid-October, peaking in early September. Ensemble machine learning models consistently achieved high predictive performance, with key predictors included urban fabric, temperature, topography, and precipitation-related indices (bio18; Köppen Aridity Index) while other factors contributed variably. Ecological associations were strongest with urbanized land cover (discontinuous and continuous urban fabric, industrial areas), specific soil types such as fluvent entisols, and humid temperate climates (Köppen Cfa). K-means clustering and decision tree analyses distinguished seven ecological clusters across Budapest, ranging from warm, densely built urban cores to cooler, shaded peri‑urban and forested zones. Conceptually linking ecological clusters to the Sustainable Development Goals highlighted spatially heterogeneous intersections with health (SDG 3), urban sustainability (SDG 11), water management (SDG 6), climate action (SDG 13), and biodiversity conservation (SDG 15). These findings provide a baseline for predicting urban vector expansion, informing early warning systems, and guiding public health interventions and vector control strategies in European metropolitan regions.
侵袭性桥梁媒介白纹伊蚊在欧洲越来越多地被发现,构成了虫媒病毒疾病传播的潜在风险。在中欧,对其扩张的城市规模评估仍然很少。Ae的建立和传播。利用时空制图、季节观测和基于指标的生态模型,并辅以集成机器学习方法,对2018年至2025年布达佩斯白纹伊蚊进行了分析。发生模式遵循logistic增长轨迹(R² = 0.995),种群分布从2020年的稀疏集中地增加到2025年的85%以上。季节性活动从4月下旬持续到10月中旬,在9月初达到高峰。集成机器学习模型始终具有较高的预测性能,其关键预测指标包括城市结构、温度、地形和降水相关指数(bio18; Köppen干旱指数),而其他因素的贡献各不相同。城市化土地覆盖(不连续和连续的城市结构、工业区)、特定土壤类型(如流土)和湿润温带气候(Köppen Cfa)的生态关联最强。K-means聚类和决策树分析区分了布达佩斯的7个生态集群,从温暖、密集的城市核心到凉爽、阴凉的城市周边和森林地区。将生态集群与可持续发展目标在概念上联系起来,强调了与健康(可持续发展目标3)、城市可持续性(可持续发展目标11)、水管理(可持续发展目标6)、气候行动(可持续发展目标13)和生物多样性保护(可持续发展目标15)在空间上的异质交叉点。这些发现为预测城市病媒扩展、告知预警系统以及指导欧洲大都市地区的公共卫生干预和病媒控制战略提供了基线。
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引用次数: 0
Temporal genomic diversity of Dengue virus in South India from 2019 to 2024 2019 - 2024年印度南部登革热病毒的时间基因组多样性
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.actatropica.2025.107934
Sudarson Sundarrajan , Santharam S Katta , Sridhar KN , Suraj Jagtap , Nagaraj C
Dengue is an endemic disease in over 100 countries, causing an estimated 500,000 hospitalizations each year. The global mortality rate for severe dengue infections is around 2.5 %. India is a major dengue hotspot, accounting for almost a third of all global cases. Despite this significant burden, there are limited studies on the circulating serotypes and genetic lineages of the dengue virus (DENV) within the country. This retrospective study investigates the distribution and genetic diversity of circulating dengue virus (DENV) variants based on clinical samples collected from healthcare centres between 2019 and 2024 in South India. A total of 1015 samples from dengue patients tested positive for at least one of the dengue NS1, IgM, or IgG markers. Among these, 210 NS1-positive samples underwent DENV serotyping via RT-PCR, and 84 of those were further characterized through Sanger sequencing of the C-prM gene to determine genotype and lineage associations. The analysis revealed a decline in dengue infection rates with increasing age, supported by a corresponding rise in IgG seropositivity. Notably, individuals under 20 years of age exhibited a significantly higher frequency of severe disease compared to older age groups. All four DENV serotypes, DENV-1 through DENV-4, were detected across the study period, with a shift in dominant serotype approximately every 2–3 years. DENV-2 and DENV-3 emerged as the most prevalent serotypes. Phylogenetic analysis identified the following genotype-lineage associations: DENV-1 as Genotype III (Lineage: 1III_A), DENV-2 as Genotype II (Cosmopolitan) (Lineages: 2II_A and 2II_F), DENV-3 as Genotype III (Lineage: 3III_B), and DENV-4 as Genotype I (Lineage: 4I_B). These findings underscore the dynamic nature of dengue virus transmission and genetic evolution in the region, emphasizing the importance of age-specific surveillance and targeted prevention strategies. This study contributes valuable insights into local DENV circulation patterns, which are critical for informing diagnostic, therapeutic, and vaccine development efforts.
登革热是100多个国家的一种地方病,每年估计造成50万人住院。严重登革热感染的全球死亡率约为2.5%。印度是登革热的主要热点,几乎占全球所有病例的三分之一。尽管有这一重大负担,但对该国登革热病毒(DENV)的流行血清型和遗传谱系的研究有限。这项回顾性研究基于2019年至2024年间从印度南部医疗中心收集的临床样本,调查了流行登革热病毒(DENV)变体的分布和遗传多样性。来自登革热患者的总共1015个样本在登革热NS1、IgM或IgG标记物中至少一种检测呈阳性。其中,210份ns1阳性样本通过RT-PCR进行DENV血清分型,其中84份通过C-prM基因的Sanger测序进一步表征,以确定基因型和谱系相关性。分析显示,随着年龄的增长,登革热感染率下降,IgG血清阳性相应上升。值得注意的是,与年龄较大的群体相比,20岁以下的个体患严重疾病的频率明显更高。在整个研究期间检测到所有四种DENV血清型,DENV-1至DENV-4,大约每2-3年发生一次优势血清型的转变。DENV-2和DENV-3是最普遍的血清型。系统发育分析发现:DENV-1为基因型III(谱系:1ii_a), DENV-2为基因型II(世界性)(谱系:2II_A和2II_F), DENV-3为基因型III(谱系:3ii_b), DENV-4为基因型I(谱系:4I_B)。这些发现强调了该地区登革热病毒传播和遗传进化的动态性质,强调了针对特定年龄的监测和有针对性的预防战略的重要性。该研究为DENV的当地传播模式提供了有价值的见解,这对于告知诊断、治疗和疫苗开发工作至关重要。
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引用次数: 0
Climate extremes and the dynamic reshaping of snail habitat: implications for the spatiotemporal heterogeneity of schistosomal vulnerability in Brazil 极端气候和蜗牛栖息地的动态重塑:对巴西血吸虫易感性时空异质性的影响。
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.actatropica.2025.107933
Amirreza Meydani , Shuai Wang , Robert Bergquist , Flavio Lopes Ribeiro , Delphis F. Levia
Extreme climate variables are increasingly important for understanding the distribution of Biomphalaria snails, the intermediate hosts of Schistosoma mansoni. While many studies focus on long-term averages, our approach emphasizes the role of climatic extreme events and their seasonal timing in shaping habitat persistence. We applied spatially explicit Random Forest (RF) species distribution models with spatial cross-validation and bootstrap aggregation to produce robust and transferable predictions of snail habitat suitability, and then ranked the influence of extreme climate variables using SHapley Additive exPlanations (SHAP) values and partial dependence plots. The models performed well, with average area under curve (AUC) values of 0.75 across species and partial AUC ratios greater than one, confirming the robustness of the predictions. Precipitation seasonality, multi-month drought indices, surface absorbed solar radiation extremes, and diurnal air temperature range were the highest-ranked drivers, though their influence was not uniform across snail species. Biomphalaria glabrata was most responsive to seasonal recharge, while B. straminea showed resilience to variability and often persisted in man-made habitats. Biomphalaria tenagophila was more constrained by drought and radiation stress. Spatial comparisons between 1995 and 2020 indicated expansions and contractions in various states, with new hotspots emerging in southeastern and central Brazil, while habitat suitability declined in drought-prone regions, such as in the State of Pernambuco. These results demonstrate that climate extreme events, in addition to long-term baseline changes, drive the spatially heterogeneous redistribution of Biomphalaria habitats. Also, our findings highlight the need for species-specific monitoring, integration of water infrastructure management, and forward-looking surveillance strategies that address both climate variability and landscapes modified by humans.
极端气候变量对了解曼氏血吸虫中间寄主生物螺的分布越来越重要。虽然许多研究侧重于长期平均值,但我们的方法强调气候极端事件及其季节时间在塑造栖息地持久性中的作用。采用空间显式随机森林(RF)物种分布模型,结合空间交叉验证和自举聚集,对蜗牛栖息地适宜性进行鲁棒性预测,并利用SHapley加性解释(SHAP)值和部分相关图对极端气候变量的影响进行排序。各物种的平均曲线下面积(AUC)值为0.75,部分AUC比值大于1,证实了模型的稳健性。降水季节性、多月干旱指数、地表吸收太阳辐射极值和日气温变化是影响螺类生长的主要因素,但对不同螺种的影响并不均匀。白僵菌对季节补给的响应最大,而白僵菌对变化的适应能力最强,并在人工生境中持续存在。B. tenagophila更受干旱和辐射胁迫的约束。1995年至2020年的空间比较表明,巴西各州的栖息地面积出现了扩张和收缩,巴西东南部和中部出现了新的热点地区,而伯南布哥州等干旱易发地区的栖息地适宜性则有所下降。这些结果表明,极端气候事件除了长期基线变化外,还驱动了Biomphalaria生境的空间异质性再分布。此外,我们的研究结果还强调了对特定物种进行监测、整合水基础设施管理和前瞻性监测战略的必要性,这些战略既要解决气候变化问题,也要解决人类改变的景观问题。
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引用次数: 0
Taxonomy and histopathology of Myxobolus mirandensis n. sp. parasite of the gills of Salminus brasiliensis from the Brazilian Pantanal wetland 巴西潘塔纳尔湿地巴西咸鱼鳃寄生米兰氏粘虫的分类与组织病理学。
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107931
Caroline M. Meira , Anna V. Serafim , Edson A. Adriano , Antonio A.M. Maia
Myxozoa are a highly diverse group of cnidarian parasites, with approximately 3070 described species. This study describes a new species, Myxobolus mirandensis n. sp., based on morphological, molecular, and histopathological analyses. The parasite was found in Salminus brasiliensis (dourado), one of the largest and most economically and recreationally important freshwater fish species in South America. Specimens of S. brasiliensis were collected from the Miranda River in the Brazilian Pantanal, with a prevalence of the infection of 63.6 % (7/11). White and elongated plasmodia were observed in the gill filaments. Pear-shaped myxospores measured 10.1 ± 0.3 µm in length, 6.6 ± 0.3 µm in width, and 5.1 ± 0.1 µm in thickness. Nematocysts were elongated and occupied more than half of the spore body, measuring 4.9 ± 0.3 µm in length and 1.9 ± 0.2 µm in width. Histopathological analysis revealed plasmodia developing in the epithelial tissue at the distal ends of the gill filaments, resulting in compression of adjacent tissues and structures. A thin connective tissue capsule surrounded the plasmodia, and numerous granulocytic cells were observed in the tissue adjacent to the plasmodia. Sequencing of the small subunit ribosomal DNA (SSU rDNA) yielded a 1954 bp fragment. Phylogenetic analysis showed M. mirandensis grouping with Myxobolus oliveirai and Myxobolus filamentum, both reported in Bryconidae hosts. This represents the seventh record of a myxozoan infecting S. brasiliensis.
黏液虫是一种高度多样化的刺胞寄生虫,大约有3070种已描述的物种。本文根据形态、分子和组织病理学分析,描述了一个新种——米兰粘虫(Myxobolus mirandensis n.sp .)。这种寄生虫是在巴西盐(Salminus brasiliensis, dourado)中发现的,巴西盐是南美洲最大、最具经济和娱乐价值的淡水鱼之一。在巴西潘塔纳尔河米兰达河采集到巴西棘球蚴标本,感染率为63.6%(7/11)。鳃丝内可见白色、细长的疟原虫。梨形黏液孢子长10.1±0.3µm,宽6.6±0.3µm,厚5.1±0.1µm。线虫囊呈细长状,占孢子体的一半以上,长4.9±0.3µm,宽1.9±0.2µm。组织病理学分析显示,疟原虫在鳃丝远端上皮组织中发育,导致邻近组织和结构受压。一层薄薄的结缔组织包膜包裹着疟原虫,在疟原虫附近的组织中可见大量粒细胞。小亚基核糖体DNA (SSU rDNA)测序得到一个1,954 bp的片段。系统发育分析表明,M. mirandensis与brycondae寄主中报道的Myxobolus oliveirai和Myxobolus filamum属同一类群。这是巴西葡萄球菌感染黏液虫的第七次记录。
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引用次数: 0
Epidemiology of the Crimean-Congo hemorrhagic fever virus 克里米亚-刚果出血热病毒的流行病学。
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107917
Neha Kaushal , Sahil Jain , Dimple Davray , Albert Rizvanov , Ming-Hsien Chiang , Olesia Ohlopkova , Svetlana Khaiboullina , Ze Chen , Manoj Baranwal
Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in >30 countries across Asia, Europe, the Middle East, and Africa. CCHFV causes Crimean-Congo hemorrhagic fever (CCHF), a disease characterized by bleeding and haemoptysis. Since the first diagnosis in 1944, 10,000–15,000 CCHF cases are reported worldwide annually. Around three billion people are at risk of CCHFV infection. The World Health Organization (WHO) announced CCHFV as a priority pathogen in December 2015 due to its widespread and significant healthcare threat. In this review, we track the outbreaks, discuss their origin, and analyze the geographical spread of the CCHFV. We will also discuss reservoirs, the modes of transmission, and the factors influencing CCHFV infection. Preventive measures will be highlighted with emphasis on the potential of artificial intelligence in outbreak prediction and disease surveillance.
克里米亚-刚果出血热病毒(CCHFV)在亚洲、欧洲、中东和非洲的30多个国家流行。克里米亚-刚果出血热(CCHF)是一种以出血和咯血为特征的疾病。自1944年首次诊断以来,全世界每年报告1万至1.5万例CCHF病例。约有30亿人面临感染CCHFV的风险。世界卫生组织(世卫组织)于2015年12月宣布CCHFV为优先病原体,因为它具有广泛和重大的卫生威胁。在这篇综述中,我们追踪了疫情,讨论了它们的起源,并分析了CCHFV的地理传播。我们还将讨论宿主、传播方式和影响CCHFV感染的因素。将强调预防措施,重点是人工智能在疫情预测和疾病监测方面的潜力。
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引用次数: 0
Evaluation of epidemiological characteristics of Crimean-Congo haemorrhagic fever patients reported to the National Surveillance System in Türkiye, 2011-2024 2011-2024年<s:1>基耶省国家监测系统报告的克里米亚-刚果出血热患者流行病学特征评估
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107925
Selda Şahan , Seher Topluoğlu , Fehminaz Temel , Yasemin Coşgun , Erdoğan Öz , Muhammed Emin Demirkol , Şuayıp Birinci
Crimean-Congo haemorrhagic fever (CCHF) is a major public health concern in Türkiye, which has the highest global incidence. This study analysed national surveillance data from 2011 to 2024 to describe the epidemiology of CCHF and identify predictors of fatality through a retrospective cohort analysis using the CCHF Information System. All laboratory-confirmed cases reported between 2011 and 2024 were included. Descriptive statistics summarized demographic, clinical, and laboratory variables. Logistic regression was applied to determine fatality predictors, and adjusted odds ratios (ORadj) with 95 % confidence intervals (CI) were calculated. Among 27,269 samples tested, 11,811 cases were laboratory-confirmed, of which 552 died (case fatality rate: 4.7 %). Males comprised 60.5 % of cases, and the mean age was 46.8 ± 18.5 years. Tick-bite or tick contact (62.2 %) and close contact with animal blood or tissues (69.6 %) were common exposure histories. Fatality was independently associated with increasing age (ORadj: 1.034; 95 % CI: 1.029–1.040), male sex (ORadj: 1.3; 95 % CI: 1.1–1.6), splenomegaly (ORadj: 2.0; 95 % CI: 1.5–2.7), haemorrhagic findings (ORadj: 2.4; 95 % CI: 2.0–3.0), platelet count <20,000/mm³ (ORadj: 10.3; 95 % CI: 6.7–15.7), platelet count 20,000–49,000/mm³ (ORadj: 4.6; 95 % CI: 3.0–7.0), and elevated AST or ALT (ORadj: 1.5; 95 % CI: 1.1–2.0). Patients who did not receive ribavirin had higher fatality (ORadj: 1.5; 95 % CI: 1.2–2.0). Although Türkiye reports many cases, fatality remains comparatively low. Identified predictors can support early risk stratification and clinical management. Strengthening surveillance, laboratory capacity, and clinician training may further reduce mortality.
克里米亚-刚果出血热(CCHF)是全球发病率最高的乌克兰的一个主要公共卫生问题。本研究分析了2011年至2024年的国家监测数据,通过使用CCHF信息系统进行回顾性队列分析,描述了CCHF的流行病学,并确定了死亡预测因素。包括2011年至2024年期间报告的所有实验室确诊病例。描述性统计总结了人口统计、临床和实验室变量。应用逻辑回归确定病死率预测因子,并计算校正优势比(ORadj)和95%置信区间(CI)。在检测的27269份样本中,有11,811例得到实验室确诊,其中552例死亡(病死率:4.7%)。男性占60.5%,平均年龄46.8±18.5岁。蜱叮咬或蜱接触(62.2%)和动物血液或组织密切接触(69.6%)是常见的暴露史。病死率与年龄增加(ORadj: 1.034; 95% CI: 1.029-1.040)、男性(ORadj: 1.3; 95% CI: 1.1-1.6)、脾肿大(ORadj: 2.0; 95% CI: 1.5-2.7)、出血(ORadj: 2.4; 95% CI: 2.0-3.0)、血小板计数独立相关。
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引用次数: 0
Ultrastructural and morphological characterization of Trypanosoma bubalisi reveals an active endocytic system 巴比利锥虫的超微结构和形态特征显示其具有活跃的内吞系统。
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107926
Ju-Feng Wang , Ying-Xin Bi , Jiong Yang , Geoff Hide , De-Hua Lai , Zhao-Rong Lun
Trypanosoma bubalisi is a newly identified mammalian trypanosome isolated from a freshwater leech (Hirudinaria manillensis) and the water buffalo (Bubalus bubalis) is considered its host. Despite the detailed morphological description of in vitro cultivated forms of this trypanosome, little is known about its ultrastructure. In this study, a detailed ultrastructure of T. bubalisi was characterized using scanning electron microscopy, transmission electron microscopy and focused ion beam-scanning electron microscopy. Two membrane-bound organelles were identified, multivesicular body-like vesicles (ve1) and large lipid-rich vesicles resembling reservosomes (ve2), alongside an extracellular ‘beads-on-a-string’ structure. These all appear to be associated with endocytosis or secretion. Three-dimensional reconstructions confirmed the organization and distribution of the two membrane-bound organelles. Functional assays using Tomato lectin and Lyso-Tracker demonstrated that ve2 is involved in endocytic uptake and may act as a terminal storage compartment. Compared to the pathogen causing Nagana, Trypanosoma brucei, T. bubalisi showed higher endocytic activity under both 27 °C and 4 °C conditions. These findings suggest that T. bubalisi possesses an active endocytic system and may share conserved mechanisms of material transport and storage with the pathogen causing Chagas’ disease, Tryponosoma cruzi.
水蛭锥虫是一种新发现的从淡水水蛭中分离出来的哺乳动物锥虫,水牛被认为是它的宿主。尽管对体外培养的锥虫有详细的形态描述,但对其超微结构知之甚少。本研究采用扫描电镜、透射电镜和聚焦离子束扫描电镜等方法,对紫毛霉的超微结构进行了详细的表征。鉴定出两种膜结合细胞器,多泡体样囊泡(ve1)和大型富含脂质的囊泡(ve2),以及细胞外的“串珠”结构。这些似乎都与内吞作用或分泌有关。三维重建证实了两个膜结合细胞器的组织和分布。使用番茄凝集素和Lyso-Tracker进行的功能分析表明,ve2参与了内吞摄取,并可能作为终端储存室。在27°C和4°C条件下,布氏锥虫均表现出较高的内吞活性。这些发现表明,南美锥虫具有活跃的内吞系统,可能与引起南美锥虫病的克氏锥虫具有相同的物质运输和储存机制。
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引用次数: 0
Repurposing disulfiram in a promising combination therapy for cryptosporidiosis in immunocompromised mice 双硫仑用于免疫功能低下小鼠隐孢子虫病的联合治疗。
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107929
Amel Youssef Shehab , Engy Mosbah Hassan , Esraa A. Moneer , Heba Essam Sedky , Fatma A. Abdelkader , Mona Mohamed Tolba , Amal Farahat Allam , Heba Elhadad
Cryptosporidiosis remains a major health concern, particularly in immunocompromised individuals, due to limited effective treatment options. Nitazoxanide (NTZ) is currently the only FDA-approved drug for cryptosporidiosis, yet its efficacy is significantly reduced in immunosuppressed hosts. This study evaluated the therapeutic potential of disulfiram, an FDA-approved drug for alcoholism, alone and in combination with NTZ, against Cryptosporidium infection in immunocompromised mice. Forty immunosuppressed Swiss albino mice were divided into five equal groups: uninfected controls, infected untreated, NTZ-treated, disulfiram-treated, and combination-treated (NTZ + disulfiram). All infected mice were orally inoculated with ∼10⁴ Cryptosporidium oocysts and were treated with NTZ (250 mg/kg/day) and/or disulfiram (25 mg/kg/day) for 10 consecutive days. Efficacy was assessed through parasitological, histopathological, and ultrastructural analyses. The combination therapy achieved the highest fecal oocyst reduction: 34.3 % after one week and 88.3 % after two weeks. In comparison, NTZ and disulfiram monotherapies achieved 24 % and 76 % reductions, respectively, at two-weeks mark. In intestinal contents, the combination therapy resulted in 62.6 % oocyst reduction versus 11.4 % for NTZ and 36.2 % for disulfiram at week two post treatment. Histopathological analysis revealed near-complete mucosal restoration in the combination group, whereas monotherapies showed limited or moderate recovery. Transmission electron microscopy confirmed full epithelial regeneration only in the dual therapy group, with intact microvilli, normal mitochondria, and restored cellular junctions. In conclusion, disulfiram, particularly when combined with NTZ, demonstrated enhanced anti-cryptosporidial efficacy and may serve as a promising adjunct therapy, mostly for immunocompromised patients.
隐孢子虫病仍然是一个主要的健康问题,特别是在免疫功能低下的个体,由于有限的有效治疗方案。Nitazoxanide (NTZ)是目前fda批准的唯一治疗隐孢子虫病的药物,但其在免疫抑制宿主中的疗效显著降低。这项研究评估了双硫仑(一种fda批准的酒精中毒药物)单独或与NTZ联合治疗免疫功能低下小鼠隐孢子虫感染的治疗潜力。40只免疫抑制的瑞士白化病小鼠被分为五组:未感染的对照组、未感染的对照组、NTZ治疗组、双硫仑治疗组和联合治疗组(NTZ + 双硫仑)。所有感染小鼠口服接种10⁴隐孢子虫卵囊,并连续10天用NTZ (250 mg/kg/天)和/或双硫仑(25 mg/kg/天)治疗。通过寄生虫学、组织病理学和超微结构分析评估疗效。联合治疗的粪卵囊肿减少率最高:一周后为34.3%,两周后为88.3%。相比之下,NTZ和双硫仑单药治疗在两周时分别减少了24%和76%。在肠道内容物方面,在治疗后第2周,联合治疗导致62.6%的卵囊减少,而NTZ组为11.4%,双硫仑组为36.2%。组织病理学分析显示,联合治疗组几乎完全恢复粘膜,而单一治疗组显示有限或中度恢复。透射电镜证实,只有双重治疗组上皮再生完全,微绒毛完整,线粒体正常,细胞连接恢复。总之,双硫仑,特别是与NTZ联合使用时,显示出增强的抗隐孢子虫功效,可能作为一种有希望的辅助治疗,主要用于免疫功能低下的患者。
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引用次数: 0
Antiparasitic Efficacy of Chalepensin from Ruta chalepensis L. Against Trichinella spiralis: In Vitro, In Vivo, and Molecular Docking Study chalepensis L. Chalepensin对旋毛虫的体外、体内及分子对接研究
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107927
Nancy E. Rodríguez-Garza , Miguel Marín , Javier Sánchez-Montejo , Ana L. Delgado-Miranda , Aldo F. Bazaldúa-Rodríguez , Ramiro Quintanilla-Licea , Azael Flores-Treviño , César I. Romo-Sáenz , Antonio Muro , Rafael Peláez , Julio López-Abán
Ruta chalepensis L. is a medicinal species widely used in ethnomedicine for gastrointestinal disorders and parasitic diseases. Among its bioactive compounds, the furanocoumarins chalepensin and graveoline have shown antiparasitic activity. This study aimed to evaluate the nematocidal potential of graveoline and chalepensin, isolated from R. chalepensis, against Trichinella spiralis in both in vitro cultures and an experimental in vivo model. The compounds were obtained from leaves and stems and first tested against first-stage larvae (L1) in culture. Selectivity indices (SI) were calculated based on cytotoxicity in Vero cells. Based on in vitro efficacy, chalepensin was selected for evaluation in a murine model of trichinellosis at 50 mg/kg/day administered over three consecutive days against three different infection stages: intestinal (days 0–2), migrating (days 13–15), and encysted (days 34–36). Larvae per gram of muscle were quantified on day 43. Histological sections were analyzed for capsule morphology and inflammation. Additionally, molecular docking was performed to explore potential parasite targets. Both compounds exhibited superior activity compared to the R. chalepensis extract (LC₅₀ = 28.2 µg/mL; SI = 22.4). Chalepensin exhibited strong in vitro activity (LC₅₀ = 0.1 µg/mL; SI = 8561), superior to graveoline (LC₅₀ = 1.1 µg/mL; SI = 162). In vivo, chalepensin reduced larval burden by 90.7% (intestinal), 37.5% (migrating), and 37.0% (encysted). Histology revealed reduced capsule thickness and pericystic inflammation. Docking predicted high affinity for thymidylate synthase (ΔG = –7.175 kcal/mol), suggesting interference with DNA synthesis. Chalepensin demonstrates potent nematocidal activity against T. spiralis, supporting its potential utility as a phytochemical-based therapeutic candidate for the management of trichinellosis.
芦丁是一种广泛应用于胃肠疾病和寄生虫病的民族医学药用植物。其生物活性成分中呋喃香豆素、chalepensin和graveoline具有抗寄生虫活性。本研究旨在评价从chalepensis中分离的graveoline和chalepensin对旋毛虫(Trichinella spiralis)的体外培养和体内实验模型的杀线虫能力。这些化合物从叶片和茎中获得,并在培养中对第一阶段幼虫(L1)进行了初步试验。根据Vero细胞毒性计算选择性指数(SI)。根据体外疗效,选择chalepensin在旋毛虫病小鼠模型中进行评估,剂量为50 mg/kg/天,连续3天给药,针对3个不同的感染阶段:肠道(0-2天)、迁移(13-15天)和成囊(34-36天)。第43天定量测定每克肌肉的幼虫数。组织切片分析胶囊形态及炎症情况。此外,还进行了分子对接,以探索潜在的寄生虫靶点。这两种化合物都比沙勒坡菌提取物具有更强的活性(LC₅₀ = 28.2µg/mL; SI = 22.4)。Chalepensin具有很强的体外活性(LC₅₀ = 0.1µg/mL; SI = 8561),优于砾石碱(LC₅₀ = 1.1µg/mL; SI = 162)。在体内,chalepensin减少了90.7%(肠道)、37.5%(迁移)和37.0%(成囊)的幼虫负担。组织学显示囊膜厚度减小,囊周炎症。对接预测胸苷酸合成酶具有高亲和力(ΔG = -7.175 kcal/mol),提示干扰DNA合成。Chalepensin显示出对螺旋体的有效杀线虫活性,支持其作为一种基于植物化学的治疗旋毛虫病的候选药物的潜在效用。
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引用次数: 0
Association of recombinant proteins rASP-2 and rTC24 from Trypanosoma cruzi as a vaccine strategy against Chagas disease induces a mixed Th1/ Th17 immune response 克氏锥虫重组蛋白rasp2和rTC24联合作为恰加斯病疫苗策略诱导混合Th1/ Th17免疫应答
IF 2.5 3区 医学 Q2 PARASITOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.actatropica.2025.107922
Bárbara da Rocha Fonseca , Guilherme Senna dos Santos , Fernanda Kanaan de Azambuja , Gustavo dos Santos Hartleben , Luiza Domingues Moron , Fernanda Severo Sabedra Souza , Fabiana Kommling Seixas , Tiago Veiras Collares , Edmundo Carlos Grisard , Sibele Borsuk
Chagas disease is a globally widespread parasitic infection caused by the flagellated protozoan Trypanosoma cruzi. It is classified as a neglected tropical disease, primarily affecting impoverished and rural regions where access to diagnosis and treatment is limited. Although treatment for this disease is effective, it is restricted to the acute phase, during which diagnosis is more challenging, reducing cure rates. Consequently, prevention remains the most effective control method, and recombinant proteins offer a promising strategy for vaccine development. Specifically, the proteins ASP-2 and TC24 have demonstrated immunoprotective activity in various experimental models. This study aimed to characterize the immune response elicited by the combined use of recombinant ASP-2 (from the intracellular stage) and TC24 (from the bloodstream stage), seeking to promote a synergistic protective effect compared to the response generated by the proteins used individually. To evaluate this, recombinant proteins rASP-2 and rTC24 were used as vaccine formulations to immunize female BALB/c mice as follows: Group 1: Saline solution; Group 2: 25 µg of rTC24 + aluminum hydroxide; Group 3: 25 µg of rASP-2 + aluminum hydroxide; Group 4: 12.5 µg of rTC24 + 12.5 µg of rASP-2 + aluminum hydroxide. The humoral immune response assessed IgG antibody levels by indirect ELISA of animal sera collected on days 0, 21, and 42 of the experiment, while the cellular response was evaluated by collecting and culturing splenocytes, assessing cytokines IFN-γ, TNF-α, interleukins 1β, 4, 6, 12, 17, and Toll-like receptor 4, quantified by real-time PCR. The results indicated a significant antibody production in the group where the proteins were combined (G4) compared to the control group (G1) on days 21 and 42. A significant increase in antibody production was also observed in group G4 on day 42 when compared to both groups using the isolated proteins (G2 and G3). Conversely, the cellular response showed an increase in IFN-γ and interleukins 1β and 17 in Group D, while the isolated ASP-2 protein induced the expression of TNF-α, interleukins 4 and 12, and Toll-like receptor 4. Western blotting using T. cruzi lysate and pooled serum confirmed the ability of the antibodies to recognize native parasite proteins. In conclusion, the combined use of proteins from different parasite life stages proved advantageous, indicating the induction of a mixed cellular immune response, predominantly of the Th1 and Th17 profiles.
恰加斯病是由有鞭毛的原生动物克氏锥虫引起的一种全球广泛传播的寄生虫感染。它被列为一种被忽视的热带病,主要影响获得诊断和治疗的机会有限的贫困和农村地区。虽然对这种疾病的治疗是有效的,但它仅限于急性期,在此期间诊断更具挑战性,降低了治愈率。因此,预防仍然是最有效的控制方法,重组蛋白为疫苗开发提供了一个有希望的策略。具体而言,ASP-2和TC24蛋白在各种实验模型中显示出免疫保护活性。本研究旨在表征重组ASP-2(来自细胞内阶段)和TC24(来自血液阶段)联合使用引发的免疫反应,与单独使用蛋白质产生的反应相比,寻求促进协同保护作用。为了验证这一点,以重组蛋白rasp2和rTC24作为疫苗配方免疫雌性BALB/c小鼠:1组:生理盐水溶液;第2组:rTC24 + 氢氧化铝25µg;第3组:25µg rasp2 + 氢氧化铝;第4组:rTC24 12.5µg + 12.5µg rasp2 + 氢氧化铝。体液免疫反应通过间接ELISA法评估实验第0、21和42天收集的动物血清中IgG抗体水平,而细胞免疫反应通过收集和培养脾细胞,评估细胞因子IFN-γ、TNF-α、白细胞介素1β、4、6、12、17和toll样受体4,通过实时PCR定量。结果表明,与对照组(G1)相比,蛋白质组合组(G4)在第21天和第42天产生了显著的抗体。与使用分离蛋白(G2和G3)的两组相比,G4组在第42天的抗体产量也显著增加。相反,D组的细胞反应显示IFN-γ和白细胞介素1β和17增加,而分离的ASP-2蛋白诱导TNF-α、白细胞介素4和12以及toll样受体4的表达。利用克氏t细胞裂解液和混合血清进行Western blotting证实了抗体识别原生寄生虫蛋白的能力。总之,结合使用来自不同寄生虫生命阶段的蛋白质证明是有利的,表明诱导混合细胞免疫反应,主要是Th1和Th17谱。
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Acta tropica
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