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Tick saliva molecules as potential immunomodulatory therapeutics 勾选唾液分子作为潜在的免疫调节疗法。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-19 DOI: 10.1016/j.parint.2025.103224
Takeshi Hatta
Ticks, infamous vectors of various pathogens, have evolved a unique strategy of saliva secretion during long-term feeding to suppress host defense mechanisms, including immune responses. This phenomenon may be a potential strategy to treat immune disorders and other diseases, offering a promising opportunity for exploiting parasite biology and parasite-derived molecules in drug discovery. This review examines the therapeutic potential of components in tick saliva, focusing on their mechanisms of action and clinical applications. It also discusses tick-derived immunomodulators, such as chemokine-binding proteins and complement inhibitors, that are currently attracting attention from the perspective of therapeutic drug development. Specifically, Ornithodoros moubata complement inhibitor (nomacopan), a C5 complement inhibitor contained in saliva from the soft tick O. moubata, has reached Phase III clinical trial status for hematopoietic stem cell transplantation-associated thrombotic microangiopathy and is considered an advanced research model in tick-derived drug development. The diverse and potent immunomodulatory properties of tick saliva molecules make them a potentially rich source for the identification and development of novel therapeutics, particularly for immune-mediated diseases.
蜱是各种病原体的臭名昭著的载体,在长期摄食过程中进化出一种独特的唾液分泌策略来抑制宿主的防御机制,包括免疫反应。这种现象可能是治疗免疫紊乱和其他疾病的潜在策略,为利用寄生虫生物学和寄生虫衍生分子进行药物发现提供了有希望的机会。本文综述了蜱虫唾液成分的治疗潜力,重点介绍了它们的作用机制和临床应用。它还讨论了蜱衍生的免疫调节剂,如趋化因子结合蛋白和补体抑制剂,目前正从治疗药物开发的角度引起关注。具体来说,moubata Ornithodoros补体抑制剂(nomacopan)是一种含有在moubata软蜱唾液中的C5补体抑制剂,已经达到了用于造血干细胞移植相关血栓性微血管病的III期临床试验状态,被认为是蜱源性药物开发的先进研究模式。蜱虫唾液分子的多样性和有效的免疫调节特性使其成为鉴定和开发新疗法的潜在丰富来源,特别是针对免疫介导的疾病。
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引用次数: 0
Corrigendum to “Parasite diversity in painted frogs inhabiting desert oases in southern Tunisia” [Parasitology International, volume 111C (2026), 103195] “居住在突尼斯南部沙漠绿洲的彩绘蛙的寄生虫多样性”的勘误表[寄生虫学国际,卷111C(2026), 103195]。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-18 DOI: 10.1016/j.parint.2025.103223
J. Dhib , M. Comas , H. Kacem , A. Hammouda , J. Harl , H.P. Fuehrer , J. Garrido-Bautista , G. Moreno-Rueda , S. Selmi
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引用次数: 0
Avian trichomonosis: An innovative approach in drug redirection with Ciprofloxacin, Norfloxacin, and Nitrofurantoin 禽滴虫病:环丙沙星、诺氟沙星和呋喃妥因药物重定向的创新方法。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-14 DOI: 10.1016/j.parint.2025.103221
Marjorie de Giacometi , Yan Wahast Islabão , Alexia Brauner de Mello , Filipe Obelar Martins , Melinda Gomes Victor , Camila Belmonte Oliveira
Trichomonas gallinae is the protozoan that causes avian trichomonosis, a disease affecting the upper digestive tract of birds and leading to proliferative lesions. The 5-nitroimidazoles, especially metronidazole, are the only recommended treatment, but emerging resistance highlights the need for alternatives. Ciprofloxacin (CP) and norfloxacin (NOR) are fluoroquinolones, and nitrofurantoin (NF) is a nitrofuran; all of which show broad-spectrum activity against bacterial and parasitic infections. This study evaluated the in vitro antiparasitic activity of these antibiotics on T. gallinae trophozoites and determined the mean inhibitory concentration (IC50), the minimum inhibitory concentration (MIC), and the mortality curve, in addition to demonstrating the morphological changes caused in the trophozoites. The antibiotics were tested at the following concentration ranges: 5–0.1 mg/mL (CP), 10–0.25 mg/mL (NOR), and 5–0.03 mg/mL (NF). Efficacy was observed at the highest concentrations (5 mg/mL for CP and NF; 10 mg/mL for NOR) after 24 h, with approximately 100 % inhibition of trophozoite growth. In the determination of IC₅₀ values, NF showed the lowest value (0.069 mg/mL), followed by CP (0.27 mg/mL) and NOR (0.71 mg/mL). The activity of antibiotics against T. gallinae began in the first hour of incubation, with over 98 % inhibition for NOR compared to approximately 65 % for CP and NF. After 12 h, inhibition of >95 % was observed, reaching 100 % in 48 h for all antibiotics. These results demonstrated that CP, NOR, and NF were promising antibiotics for the in vitro treatment of avian trichomonosis. All tested antibiotics induced significant morphological changes in trophozoites, including flagellar internalization, vacuolization, and pseudocyst-like formations. In silico studies were carried out with relevant Trichomonas proteins which showed potential mechanistic pathways of CP and NOR.
鸡毛滴虫是引起禽毛滴虫病的原生动物,禽毛滴虫病是一种影响鸟类上消化道并导致增殖性病变的疾病。5-硝基咪唑,特别是甲硝唑,是唯一推荐的治疗方法,但新出现的耐药性突出了寻找替代品的必要性。环丙沙星(CP)和诺氟沙星(NOR)为氟喹诺酮类药物,呋喃妥因(NF)为呋喃类药物;所有这些都显示出对细菌和寄生虫感染的广谱活性。本研究评估了这些抗生素对鸡糜虫滋养体的体外抗寄生活性,测定了平均抑制浓度(IC50)、最低抑制浓度(MIC)和死亡曲线,并证明了滋养体的形态变化。抗生素检测浓度范围为5-0.1 mg/mL (CP)、10-0.25 mg/mL (NOR)和5-0.03 mg/mL (NF)。24 h后,在最高浓度(CP和NF为5 mg/mL; NOR为10 mg/mL)下观察到效果,对滋养体生长的抑制作用约为100% %。在确定IC₅0值时,NF显示出最低值(0.069 mg/mL),其次是CP(0.27 mg/mL)和NOR(0.71 mg/mL)。抗生素对鸡绦虫的活性在孵育的第一个小时开始,对NOR的抑制作用超过98% %,而对CP和NF的抑制作用约为65% %。12 h后,观察到>的抑制率为95% %,48 h后,所有抗生素的抑制率均达到100% %。这些结果表明,CP、NOR和NF是体外治疗禽滴虫病有前景的抗生素。所有测试的抗生素都引起滋养体的显著形态变化,包括鞭毛内化、空泡化和假囊肿样形成。用相关毛滴虫蛋白进行了计算机研究,揭示了CP和NOR的潜在机制途径。
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引用次数: 0
Cryptosporidium spp. in adult goats from family farms in northwestern Argentina: Prevalence and epidemiological insights 阿根廷西北部家庭农场成年山羊隐孢子虫的流行病学研究。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-11 DOI: 10.1016/j.parint.2025.103222
Carina Basset , Kevin D. Steffen , Lorena De Felice , Bruno Fitte , Paula L. Olaizola , M. Laura Gos , Juan M. Unzaga
Cryptosporidium infection in goats has been reported in several countries. However, information is scarce for South America, including Argentina. This study aimed to identify Cryptosporidium spp. infections in adult goats of 11 rural communities from Luracatao Valley (Argentina), and to evaluate associated risk factors through socio-productive surveys. Fecal samples were collected of 409 adult goats from 51 family farms. Oocysts compatible with Cryptosporidium spp. were detected in 0.48 % (2/409) of samples by microscopy. A total of 4.89 % (20/409) of goats and 36.36 % (4/11) of communities tested positive by nested PCR targeting 18S rRNA gene fragments. The sequences were consistent with C. ubiquitum (n = 15), C. xiaoi (n = 3), and C. parvum (n = 2). 51 surveys were conducted with goat-raising families, providing contextual data on herd management, health practices, and environmental conditions. Multivariate analysis showed a significant protective association between antiparasitic treatment and Cryptosporidium infection (OR = 0.073; p < 0.05). These findings provide valuable information to better understand cryptosporidiosis in family goat systems, a system that is often overlooked in public policy, despite goats being a significant source of livelihood for many families.
一些国家报告了山羊中隐孢子虫感染。然而,包括阿根廷在内的南美洲的信息很少。本研究旨在鉴定阿根廷Luracatao山谷11个农村社区成年山羊隐孢子虫感染情况,并通过社会生产调查评估相关危险因素。收集了51个家庭农场409只成年山羊的粪便样本。显微镜下检出与隐孢子虫相容的卵囊率为0.48 %(2/409)。针对18S rRNA基因片段进行巢式PCR检测,共有4.89 %(20/409)的山羊和36.36 %(4/11)的群落呈阳性。与C. ubiquitum (n = 15)、C. xiaoi (n = 3)和C. parvum (n = 2)序列一致。对山羊饲养家庭进行了51次调查,提供了关于羊群管理、卫生做法和环境条件的背景数据。多因素分析显示,抗寄生虫治疗与隐孢子虫感染之间存在显著的保护性关联(OR = 0.073;p
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引用次数: 0
Nocardia-derived metabolites as promising antibacterial and larvicidal agents against Anopheles stephensi (Diptera: Culicidae) 诺卡菌衍生代谢物作为抗斯氏按蚊(双翅目:库蚊科)的有前景的抗菌和杀幼虫剂。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-10 DOI: 10.1016/j.parint.2025.103220
Marjan Seratnahaei , Saeed Eshraghi , Fatemeh Safari , Snigdha Mohan , Neda Merikhi , Leila shirani-bidabadi , Alireza Zahraei-Ramazani
Nocardia species produce diverse bioactive secondary metabolites, with potential applications against antibiotic resistance and vector-borne diseases. This study characterizes a metabolite from Nocardia fluminea strain N2, isolated from soils in Tehran, Iran, and evaluates its dual antibacterial and larvicidal activities. The strain, identified via 16S rRNA sequencing, and its metabolite production was monitored. Antibacterial efficacy was assessed using agar well diffusion and Minimum Inhibitory Concentration (MIC) assays, while larvicidal toxicity was evaluated by determining the Lethal Concentration 50 (LC₅₀) and 90 (LC₉₀). The metabolite's chemical composition was elucidated using High-Performance Liquid Chromatography (HPLC) and mass spectrometry. The metabolite exhibited potent antibacterial effects, demonstrating significant inhibition zones (>15 mm) and low MIC against Escherichia coli (6.67 μg/mL) and Salmonella typhimurium (2.67 μg/mL). In larvicidal assays against Anopheles stephensi, the metabolite showed time-dependent efficacy, with LC₅₀ values decreasing from 399 mg/L at 24 h to 353 mg/L at 72 h. Structural analysis suggested a novel compound with a molecular weight of 738 Da. Our findings identify the N. fluminea N2 metabolite as a promising dual-function agent for combating bacterial pathogens and malaria vectors.
诺卡菌产生多种生物活性次生代谢物,具有抗抗生素耐药性和媒介传播疾病的潜在应用。本研究鉴定了从伊朗德黑兰土壤中分离的流感诺卡菌N2株的代谢物,并评价了其抗菌和杀幼虫的双重活性。通过16S rRNA测序鉴定该菌株,并监测其代谢产物的产生。使用琼脂孔扩散和最低抑制浓度(MIC)测定来评估抗菌效果,而通过确定致死浓度50 (LC₅₀)和90 (LC₉₀)来评估杀幼虫毒性。采用高效液相色谱(HPLC)和质谱法对其化学成分进行了分析。该代谢物对大肠杆菌(6.67 μg/mL)和鼠伤寒沙门菌(2.67 μg/mL)具有显著的抑制区(bbb15 mm)和低MIC,具有较强的抑菌作用。在对斯氏按蚊的杀幼虫试验中,代谢物显示出时间依赖性的功效,LC₅0值从24 h时的399 mg/L下降到72 h时的353 mg/L。结构分析表明该化合物分子量为738 Da。我们的研究结果表明,氟奈米菌N2代谢物是一种很有前途的双功能剂,可用于对抗细菌病原体和疟疾媒介。
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引用次数: 0
First identification of the Africa 4 genotype of toxoplasma gondii in Algeria: Investigation of its origin and rarity 阿尔及利亚首次发现刚地弓形虫非洲4基因型:起源和罕见度调查。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.parint.2025.103212
Nabil Mohamdi , Sihem Benaissa , Anis Benyahia , Karine Passebosc-Faure , Hélène Yéra , Gilles Gargala , Damien Costa , Loic Favennec
Toxoplasmosis, a parasitic infection caused by Toxoplasma gondii, is widely distributed worldwide. Although it generally remains asymptomatic in immunocompetent individuals, it can lead to severe complications in immunocompromised patients, particularly those infected with HIV. These individuals are at increased risk of developing encephalitis, primarily due to the reactivation of a latent infection. Genotyping of T. gondii in humans is an essential tool for studying the epidemiology of this parasitosis. Previous studies have identified three main archetypal (classical) lineages or genotypes: type I, II, and III, as well as strains that show distinct and broader genetic variations.
In this study, we report for the first time in Algeria the isolation and genetic characterization of the Africa 4 lineage of Toxoplasma gondii using microsatellites genotyping in an HIV-positive patient. This recently described clonal lineage in animal and human highlights the genetic diversity of T. gondii. This work underscores the need for studies to explore the prevalence and distribution of genotypes in the Maghreb region.
弓形虫病是由刚地弓形虫引起的一种寄生虫感染,在世界范围内广泛分布。尽管在免疫正常的个体中,它通常没有症状,但在免疫功能低下的患者中,特别是那些感染了艾滋病毒的患者,它可能导致严重的并发症。这些人患脑炎的风险增加,主要是由于潜伏感染的重新激活。人类弓形虫基因分型是研究该寄生虫病流行病学的重要工具。先前的研究已经确定了三种主要的原型(经典)谱系或基因型:I型,II型和III型,以及表现出明显和广泛的遗传变异的菌株。在这项研究中,我们首次在阿尔及利亚报道了用微卫星基因分型方法从一名hiv阳性患者中分离出非洲4系刚地弓形虫并对其进行遗传鉴定。最近在动物中描述的克隆谱系突出了目前在人类中报道的弓形虫的遗传多样性。这项工作强调需要进行研究,探索基因型的流行和分布在马格里布地区。
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引用次数: 0
Toxoplasma gondii and Neospora caninum in naturally infected synanthropic (Muridae) and wild (Cricetidae) rodents from Argentina 阿根廷自然感染的合群(鼠科)和野生(鼠科)啮齿动物中的刚地弓形虫和犬新孢子虫。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.parint.2025.103204
Judith V. Bentancourt Rossoli , Lucía María Campero , Gastón Moré , Agustina Soto-Cabrera , Dadín P. Moore , Eleonora L. Morrell , María V. Scioli , Walter Basso , Yanina P. Hecker , Nathalia P. Scioscia
Rodents serve as reservoir hosts for many parasites, including the closely related intracellular protozoan parasites Toxoplasma gondii and Neospora caninum, which are regarded as major causes of abortion in ruminants. This study investigated T. gondii and N. caninum infections in synanthropic (Muridae) and wild (Cricetidae) rodents from rural areas in the Pampas Region, Argentina, using histological, serological, and molecular methods. We also genetically characterized T. gondii isolates. A total of 356 rodents were captured, comprising both murid (Mus musculus, Rattus norvegicus, R. rattus) and cricetid (Oxymycterus rufus, Necromys spp., Akodon azarae, Oligoryzomys flavescens, Calomys musculinus, C. laucha) species. Histological examination did not reveal tissue cysts of these parasites. However, antibodies for T. gondii and N. caninum were detected in 9.8 % (35/356) and 1.7 % (6/356) of the samples using the indirect immunofluorescent antibody test (IFAT). T. gondii DNA was detected by qPCR in brain samples from two of the 41 seropositive rodents. Multilocus PCR-RFLP revealed atypical T. gondii genotypes in both samples. N. caninum DNA was not detected by PCR in any sample. This study provides the first serological and molecular evidence of T. gondii and N. caninum in Cricetidae rodents from Argentina, including the first genotyping data. The detection of T. gondii DNA exclusively in wild rodents highlights the role of wildlife in parasite transmission.
啮齿类动物是许多寄生虫的宿主,包括密切相关的细胞内原生动物寄生虫刚地弓形虫和犬新孢子虫,它们被认为是反刍动物流产的主要原因。本研究采用组织学、血清学和分子方法调查了阿根廷潘帕斯地区农村合群(鼠科)和野生(鼠科)啮齿动物中弓形虫和犬奈虫的感染情况。我们还对刚地弓形虫分离株进行了遗传表征。共捕获鼠类356只,包括鼠类(小家鼠、褐家鼠、家鼠)和家鼠类(褐家鼠、褐家鼠、扎扎家鼠、黄褐家鼠、褐家鼠、褐家鼠、褐家鼠、褐家鼠)。组织学检查未见组织囊肿。间接免疫荧光抗体检测(IFAT)分别检测到9.8 %(35/356)和1.7 %(6/356)的弓形虫和犬原体抗体。用qPCR方法在41只血清阳性啮齿动物中2只的脑样本中检测到弓形虫DNA。多位点PCR-RFLP结果显示,两份样本均存在非典型弓形虫基因型。所有样品均未检测到犬乳杆菌DNA。本研究首次提供了阿根廷cricedae啮齿动物中弓形虫和犬奈虫的血清学和分子证据,包括首次基因分型数据。仅在野生啮齿动物中检测到弓形虫DNA,突出了野生动物在寄生虫传播中的作用。
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引用次数: 0
Seroprevalence and associated risk factors of human fascioliasis in Yen Bai and Thanh Hoa provinces, Vietnam 越南银白省和清化省人类片形吸虫病的血清患病率及相关危险因素
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.parint.2025.103219
Thao Thi Bich Nguyen , Hafid Dahma , Veronique Dermauw , Dung Thi Bui , Bertrand Losson , Pierre Dorny , Dung Trung Do , Olivier Vandenberg
Fascioliasis is a zoonotic disease that affects human and animal health worldwide, especially in developing countries. Although fascioliasis is considered an emerging disease in Vietnam, community-based prevalence estimates are scarce. This study aimed to assess the prevalence and risk factors of fascioliasis in northern Vietnam. In 2018, a cross-sectional study was conducted involving 796 individuals from Yen Bai and Thanh Hoa provinces; stool and blood samples were collected from its members. Stool samples were analyzed for Fasciola eggs using the Kato-Katz and formalin-ether concentration techniques, while serum samples were analyzed for anti-Fasciola antibodies using ELISA. All participants aged 15 years and older completed a questionnaire on demographic characteristics and culinary practices. No Fasciola eggs were detected in stool samples (0 %, 95 %CI: 0.00–0.46); however, 2.6 % of participants were seropositive for fascioliasis (21/796, 95 %CI: 1.7 % – 4.0 %). Multivariable logistic regression showed a significantly higher risk of being seropositive among individuals of non-Kinh ethnicity (OR = 14.03, 95 % CI: 2.39–82.17), and among farmers (OR = 3.42, 95 % CI: 1.04–11.25). Lack of awareness about fascioliasis was associated with higher seropositivity (OR = 0.31, 95 %CI: 0.11–0.87). Our findings indicate that fascioliasis is mesoendemic in northern and north central Vietnam. Targeted educational campaigns should explain how transmission can be interrupted.
片形吸虫病是一种人畜共患疾病,影响全世界,特别是发展中国家的人类和动物健康。尽管片形吸虫病在越南被认为是一种新出现的疾病,但基于社区的患病率估计很少。本研究旨在评估越南北部片形吸虫病的流行情况和危险因素。2018年,对来自严白和清化省的796人进行了一项横断面研究;收集了其成员的粪便和血液样本。采用Kato-Katz和福尔马林乙醚浓度技术对粪便样本进行片形吸虫卵检测,采用ELISA法对血清样本进行抗片形吸虫抗体检测。所有年龄在 岁及以上的参与者都完成了一份关于人口特征和烹饪实践的问卷调查。粪便标本未检出片形吸虫卵(0 %,95 %CI: 0.00 ~ 0.46);然而,2.6 %的参与者片形吸虫病血清阳性(21/796,95 %CI: 1.7 % - 4.0% %)。多变量logistic回归显示,非kinh族个体(OR = 14.03,95 % CI: 2.39-82.17)和农民(OR = 3.42,95 % CI: 1.04-11.25)的血清阳性风险显著较高。缺乏对片形吸虫病的认识与较高的血清阳性相关(OR = 0.31,95 %CI: 0.11-0.87)。我们的研究结果表明,片形吸虫病在越南北部和中北部是中地方性的。有针对性的教育运动应解释如何阻断传播。
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引用次数: 0
Novel diversity and distributions of myxozoans in amphibians from Ecuador with the description of a new species of Cystodiscus 厄瓜多尔两栖动物黏液动物的新多样性和分布与囊盘一新种的描述。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.parint.2025.103218
Gabriela B. Bittencourt-Silva , Gema Alama-Bermejo , Rebecca Higham , Santiago R. Ron , Beth Okamura , Jeffrey W. Streicher
Among parasites with vertebrate hosts, myxozoans (Cnidaria) remain some of the least studied both taxonomically and geographically. We conducted the first reported surveys for myxozoans from amphibian hosts in Ecuador at two localities: a mid-elevation cloud forest on the Chocó region (western slopes of the Andes) and a lowland Amazonian tropical forest, east of the Andes. We sampled 177 gall bladders and 17 kidneys across the surveys. We found no evidence of myxozoans in the cloud forest site. Myxozoans of the genus Cystodiscus were encountered in the gallbladders of multiple amphibian species from the Amazonian rainforest site, including new host records. Our molecular phylogenies show that, while many of these myxozoans were referable to a clade of C. cf. immersus, we also discovered a divergent lineage of Cystodiscus in the gall bladder of a host that, unlike other known amphibian hosts, has arboreal oviposition. We describe this lineage as a new species, Cystodiscus insperatus n. sp., and infer transmission scenarios consistent with the unique ecology of its frog host. We also report for the first time molecular evidence of a possible new lineage of Sphaerospora living in the kidneys of Osteocephalus taurinus (Anura). Collectively, our study highlights the potential for (i) large biogeographic barriers (like the Andes) to influence the distribution of myxozoans and (ii) intermediate host ecology to drive the evolution of novel lineages of these parasites.
在以脊椎动物为寄主的寄生虫中,粘虫(刺胞虫)在分类学和地理上都是研究最少的。我们在厄瓜多尔的两个地方进行了首次两栖类黏液动物调查:Chocó地区(安第斯山脉西部斜坡)的中高海拔云雾森林和安第斯山脉东部的亚马逊低地热带森林。我们在调查中抽取了177个胆囊和17个肾脏。我们在云雾森林遗址没有发现黏液动物的证据。在亚马逊雨林遗址的多种两栖动物的胆囊中发现了囊盘属黏液动物,包括新的寄主记录。我们的分子系统发育表明,虽然这些黏液动物中的许多都与c.c.s immersus的一个分支有关,但我们也在宿主的胆囊中发现了一个不同的囊盘动物谱系,与其他已知的两栖动物宿主不同,它有树栖产卵。我们将这一谱系描述为一个新的物种,囊蝇insperatus n. sp.,并推断其传播情景与它的青蛙宿主的独特生态相一致。我们也首次报道了在牛头骨头(Osteocephalus taurinus, Anura)的肾脏中可能存在的Sphaerospora新谱系的分子证据。总的来说,我们的研究强调了(i)大型生物地理屏障(如安第斯山脉)影响黏着动物分布和(ii)中间宿主生态驱动这些寄生虫新谱系进化的潜力。
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引用次数: 0
Recombinant small myristoylated protein-3 and synthetic peptide as diagnostic and prognostic biomarkers for tegumentary leishmaniasis 重组小肉豆酰化蛋白-3和合成肽作为被膜利什曼病诊断和预后的生物标志物。
IF 1.9 4区 医学 Q3 PARASITOLOGY Pub Date : 2025-11-30 DOI: 10.1016/j.parint.2025.103213
Maíza M. Rodrigues , Raquel S.B. Câmara , Camila S. Freitas , Daniela P. Lage , Ana L. Silva , Mariana M. Cardoso , Nathália C. Galvani , Dóris M. Abrão , Breno L. Pimenta , Bárbara P.N. Assis , Ana T. Chaves , Grasiele S.V. Tavares , João A. Oliveira-da-Silva , Unaí Tupinambás , Manoel O. da Costa Rocha , Myron Christodoulides , Ricardo A. Machado-de-Ávila , Denise U. Gonçalves , Isabela A.G. Pereira , Eduardo A.F. Coelho
The diagnosis of tegumentary leishmaniasis (TL) remains challenging, primarily due to the variable sensitivity and specificity of current laboratory tests. Moreover, most diagnostic methods rely on invasive blood collection and require laboratory infrastructure, limiting their accessibility. In this study, the Leishmania small myristoylated protein-3 (SMP-3) was evaluated as a potential diagnostic antigen for TL using both urine and serum samples. A total of 175 paired samples were analyzed, including 55 from TL patients, 45 from healthy individuals, and 75 from patients with cross-reactive diseases. The diagnostic performance of recombinant SMP-3 (rSMP-3), a predicted B-cell epitope from the SMP-3 sequence, and a soluble Leishmania (Viannia) braziliensis antigen extract (SLA) were assessed using ELISA experiments. In urine-based ELISA, rSMP-3 demonstrated excellent diagnostic accuracy, with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa coefficient all reaching 100 %. The synthetic peptide yielded sensitivity of 87.3 %, specificity of 100 %, PPV of 1.0, NPV of 0.95, and a kappa of 0.89. In comparison, SLA showed lower performance with values of 76.6 % sensitivity, 93.3 % specificity, 0.84 PPV, 0.90 NPV, and 0.73 kappa coefficient. For serum-based ELISA, rSMP-3 also exhibited high diagnostic performance, with sensitivity of 90.9 %, specificity of 100 %, PPV of 1.0, NPV of 0.96, and a kappa of 0.93. The synthetic peptide reached 94.6 % sensitivity, 96.7 % specificity, 0.96 PPV, 0.95 NPV, and a kappa of 0.91. SLA again showed inferior results, with sensitivity of 50.9 %, specificity of 94.2 %, PPV of 0.94, NPV of 0.92, and a kappa coefficient of 0.50. Furthermore, a significant decline in SMP-3-specific IgG levels was observed six months post-treatment in TL patients, indicating its potential utility as a prognostic marker. When compared to a commercial diagnostic kit, SMP-3 demonstrated satisfactory performance. In conclusion, SMP-3 is a promising antigen for the non-invasive diagnosis and monitoring of TL and warrants further investigation as a diagnostic and prognostic tool for this neglected tropical disease.
囊状利什曼病(TL)的诊断仍然具有挑战性,主要是由于目前实验室检测的敏感性和特异性不同。此外,大多数诊断方法依赖于侵入性采血,需要实验室基础设施,限制了其可及性。在这项研究中,利什曼原虫小肉豆芽酰化蛋白-3 (SMP-3)作为一种潜在的诊断抗原,通过尿液和血清样本进行评估。共分析了175个配对样本,其中55个来自TL患者,45个来自健康个体,75个来自交叉反应性疾病患者。采用酶联免疫吸附试验(ELISA)评价重组SMP-3 (rSMP-3)、SMP-3序列预测的b细胞表位和可溶性巴西利什曼原虫抗原提取物(SLA)的诊断性能。在基于尿液的ELISA中,rSMP-3表现出良好的诊断准确性,其敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV)和kappa系数均达到100% %。合成肽的敏感性为87.3 %,特异性为100 %,PPV为1.0,NPV为0.95,kappa为0.89。相比之下,SLA表现出较低的性能,敏感性为76.6% %,特异性为93.3 %,PPV为0.84,NPV为0.90,kappa系数为0.73。在基于血清的ELISA中,rSMP-3也表现出较高的诊断性能,灵敏度为90.9 %,特异性为100 %,PPV为1.0,NPV为0.96,kappa为0.93。合成肽的敏感性为94.6 %,特异性为96.7 %,PPV为0.96,NPV为0.95,kappa为0.91。SLA再次显示较差的结果,敏感性为50.9 %,特异性为94.2 %,PPV为0.94,NPV为0.92,kappa系数为0.50。此外,治疗后6个月观察到TL患者smp -3特异性IgG水平显著下降,表明其作为预后指标的潜在效用。与商用诊断试剂盒相比,SMP-3表现出令人满意的性能。总之,SMP-3是一种有希望用于TL非侵入性诊断和监测的抗原,值得进一步研究作为这种被忽视的热带病的诊断和预后工具。
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