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Habu vipers (Protobothrops flavoviridis) are an overlooked but important reservoir of the zoonotic tick Amblyomma testudinarium (Acari: Ixodidae) in subtropical Asia. 哈布毒蛇(Protobothrops flavoviridis)是亚热带亚洲人畜共患病蜱虫Amblyomma testudinarium(Acari: Ixodidae)的一个被忽视但却重要的贮藏库。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.actatropica.2024.107472
Mackenzie L Kwak, Shintaro Nakagawa, So Shinya, Paula Andrea Jiménez, Greg Markowsky, Daniel McInnes, Yurie Taya, Shouta M M Nakayama, Mayumi Ishizuka, Nariaki Nonaka, Ryo Nakao

Subtropical Asia has a rich diversity of reptiles and ticks, though the role of reptiles in the sylvatic cycles of medically important ticks in the region is poorly known. Habu vipers (Protobothrops flavoviridis) are widespread and common in the Japanese subtropics but their role as hosts for ticks has not been carefully explored. For 15 months in 2023/24, habu vipers were screened for ticks and were found to be important hosts for immature stages of the tick Amblyomma testudinarium, with a 22% infestation rate. Amblyomma testudinarium was found to have weak attachment site preferences on P. flavoviridis and host body length was found to have no relationship with either the risk of infestation or the tick load in infested snakes. The phenological profile of A. testudinarium was mapped for the first time in the subtropics based on mean tick loads on P. flavoviridis and historical flagging data. March-April were identified as the period of highest activity, May to July was a period of declining activity, August-September was a period of almost complete inactivity, and October to February was a periods of increasing activity. The role of habu vipers in the sylvatic cycle of A. testudinarium in subtropical Asia is discussion. Additionally, the potential of habu vipers to serve as reservoirs of pathogens or as dilution hosts is also explored.

亚洲亚热带地区拥有丰富多样的爬行动物和蜱虫,但爬行动物在该地区具有重要医疗价值的蜱虫的寄生周期中所起的作用却鲜为人知。哈布蝮蛇(Protobothrops flavoviridis)在日本亚热带地区广泛分布,十分常见,但它们作为蜱虫宿主的作用尚未得到仔细研究。在 2023/24 年的 15 个月中,对哈布蝰进行了蜱虫筛查,发现它们是蜱虫 Amblyomma testudinarium 未成年阶段的重要宿主,感染率为 22%。研究发现,Amblyomma testudinarium对P. flavoviridis的附着部位偏好较弱,宿主体长与受感染蛇类的感染风险或蜱载量均无关系。根据黄花蜱的平均负载量和历史标记数据,首次绘制了亚热带地区黄花蜱的物候轮廓图。结果表明,3 月至 4 月是活动最频繁的时期,5 月至 7 月是活动减少的时期,8 月至 9 月是几乎完全不活动的时期,10 月至 2 月是活动增加的时期。本文讨论了哈布蝰在亚洲亚热带地区睾丸蝮蛇活动周期中的作用。此外,还探讨了哈布蝰作为病原体储库或稀释宿主的潜力。
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引用次数: 0
Harnessing computational and experimental approaches to identify potent hits against Leishmania donovani sterol C-24 methyltransferase from ChemBridge library. 利用计算和实验方法,从 ChemBridge 库中找出对唐氏利什曼原虫甾醇 C-24 甲基转移酶有特效的药物。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.actatropica.2024.107473
Diksha Kumari, Tashi Palmo, Somdutt Mujwar, Kuljit Singh

Leishmaniasis is a neglected tropical disease and is one of the major causes of mortality in poverty-stricken areas. A limited chemotherapeutics arsenal is available to tackle this deadly infection. Thus, identifying novel potent scaffolds using innovative strategies is the need of the hour. High-throughput screening (HTS) is a critical technique that can accelerate the process of drug discovery by evaluating millions of drug-like molecules using various automation tools and biological assays. In the present study, we have employed the HTS strategy to identify potent hits against Leishmania donovani sterol C-24 methyltransferase (LdSMT) from the in-house ChemBridge library. Firstly, a robust dataset was prepared with previously reported sterol C-24 methyltransferase inhibitors, belonging to diverse structural classes. Then, ligand-based virtual screening using similarity search was performed to screen the ChemBridge library having ∼20,000 molecules. This computational approach yielded 81 candidate compounds, which were selected for further molecular docking and biological evaluation. Anti-leishmanial assays revealed that out of 81 molecules, seven showed potential parasitic killing. Three molecules namely IIIM-CB-14, IIIM-CB-29, and IIIM-CB-45 were the most potent ones with 50% inhibitory concentration (IC50) of 5.76, 8.08, and 10.64 µg/mL, respectively. SEM analyses suggest that these potent hits cause considerable morphological alterations. ADME studies of the potent hit molecules indicate that all the hits have considerable drug-likeness properties. Further, molecular dynamics studies were also performed to check the stable confirmation of LdSMT protein with the top two hits (IIIM-CB-14 and IIIM-CB-45). Thus, the present study harnesses computational and experimental approaches to unravel potent anti-leishmanial scaffolds.

利什曼病是一种被忽视的热带疾病,也是贫困地区死亡的主要原因之一。目前可用于应对这种致命感染的化疗药物有限。因此,利用创新策略确定新型强效支架是当务之急。高通量筛选(HTS)是一项关键技术,它能利用各种自动化工具和生物检测方法评估数百万个类药物分子,从而加速药物发现过程。在本研究中,我们采用了 HTS 策略,从内部 ChemBridge 库中筛选出针对唐氏利什曼原虫甾醇 C-24 甲基转移酶(LdSMT)的有效药物。首先,利用以前报道过的不同结构类别的甾醇 C-24 甲基转移酶抑制剂建立了一个强大的数据集。然后,利用相似性搜索进行配体虚拟筛选,对 ChemBridge 库中的 20,000 个分子进行筛选。通过这种计算方法,共筛选出 81 个候选化合物,并对它们进行了进一步的分子对接和生物学评估。抗利什曼病试验显示,在 81 个分子中,有 7 个具有潜在的杀寄生虫作用。其中三个分子,即 IIIM-CB-14、IIIM-CB-29 和 IIIM-CB-45 的药效最强,其 50% 抑制浓度 (IC50) 分别为 5.76、8.08 和 10.64 µg/mL。扫描电子显微镜分析表明,这些强效化合物会引起相当大的形态学改变。对强效命中分子的 ADME 研究表明,所有命中分子都具有相当的药物相似性。此外,还进行了分子动力学研究,以检查 LdSMT 蛋白与前两个命中分子(IIIM-CB-14 和 IIIM-CB-45)的稳定确认情况。因此,本研究利用计算和实验方法揭示了有效的抗利什曼病菌支架。
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引用次数: 0
A methodological proposal to estimate the total abundance of immature mosquitoes in discarded tyres: Aedes aegypti and Culex pipiens as study cases. 估算废弃轮胎中未成熟蚊子总丰度的方法建议:以埃及伊蚊和喙库蚊为研究案例。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-15 DOI: 10.1016/j.actatropica.2024.107474
Julieta A Achaga, Darío Vezzani

Estimating the abundance of immature mosquitoes in discarded water-filled tyres is a laborious task due to their shape and size. Our objective was to develop a procedure that allows, by counting individuals in a water sample, to estimate their total abundance. Polynomial functions linking water column height and water volume were fitted for five tyre categories (from cars to tractors) and horizontal/vertical storage positions. A total of 358 discarded water-filled tyres were then surveyed using this method in 16 piles of tyres in temperate Argentina. Tyre capacity was greater in vertical than horizontal position, reaching a maximum of 95.6 L in tractor tyres. In contrast, the volume of water retained under field conditions showed the opposite pattern, being greater in horizontal tyres. Water volume increased significantly across tyre categories in both horizontal (J-T=7306, p<0.001) and vertical (J-T=10792, p<0.001) positions. Most infested tyres (n=150) showed low abundances and a few extremely high values, both for all mosquito species grouped and for Culex pipiens and Aedes aegypti separately. The median abundance of mosquitoes per infested tyre was 35, decreasing to 30 for Cx. pipiens and 17 for Ae. aegypti. These values ​​increased significantly across tyre categories for mosquitoes (J-T=5525, p<0.001) and Cx. pipiens (J-T=2275, p<0.05), but not for Ae. aegypti (J-T=1526, p=0.472). The comparison between vertical and horizontal positions was not significant for both vector species. Our methodological approach could be particularly useful in research addressing the assessment of disease risk associated with mosquito productivity.

由于蚊子的形状和大小,估算废弃注水轮胎中未成熟蚊子的数量是一项费力的工作。我们的目标是开发一种程序,通过对水样中的个体进行计数,来估算它们的总数量。我们针对五种轮胎类别(从汽车到拖拉机)和水平/垂直储存位置,拟合了连接水柱高度和水量的多项式函数。然后,采用这种方法对阿根廷温带地区 16 个轮胎堆中的 358 个废弃充水轮胎进行了调查。垂直位置的轮胎容量大于水平位置,拖拉机轮胎的最大容量为 95.6 升。相比之下,田间条件下的留水量则显示出相反的模式,水平位置的轮胎留水量更大。在不同的轮胎类别中,水平轮胎的留水量都有明显增加(J-T=7306,p<0.05)。
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引用次数: 0
Evidence of endogenous Non-retroviral RNA Virus Sequences into the genome and transcriptome of the malaria vector Anopheles darlingi. 疟疾病媒达疟蚊基因组和转录组中存在内源性非逆转录 RNA 病毒序列的证据。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-14 DOI: 10.1016/j.actatropica.2024.107469
Juan C Hernandez-Valencia, Paola Muñoz-Laiton, Giovan F Gómez, Margarita M Correa

The characterization of non-retroviral integrated RNA virus sequences (NIRVS) in mosquitoes has emerged as a significant area of research that could yield insight into virus-host interactions. This study aimed to characterize NIRVS in the Anopheles darlingi reference genome and identify putative transcribed NIRVS in field-collected mosquitoes from Colombia. The An. darlingi reference genome was analyzed to identify and characterize NIRVS by conducting a BLAST query with all the virus sequences previously identified in arthropods available in the NCBI-virus repository. In addition, An. darlingi field-collected mosquitoes were examined for NIRVS using a metatranscriptomic approach. As a result, 44 NIRVS were identified in the An. darlingi genome, constituting integrations of negative single-stranded RNA viruses (ssRNA-) from the families Rhabdoviridae, Chuviridae and Phasmaviridae, and integrations of double-stranded RNA viruses (dsRNA) from the families Partitiviridae and Sedoreoviridae. These NIRVS were not randomly distributed but clustered in specific regions of the genome enriched with BEL/Pao and Ty3/Gypsy long terminal repeat elements. Furthermore, putative NIRVS-like sequences were present in the transcriptomic data from all the Colombian An. darlingi natural populations. This study is significant as it represents the first identification of NIRVS in the most important malaria vector of the Neotropics. The findings help in understanding the intricate relationship between the mosquito and its virome, and the regulation of viruses' mechanisms in the Anopheles genus.

蚊子体内非逆转录病毒整合 RNA 病毒序列(NIRVS)的特征描述已成为一个重要的研究领域,可以深入了解病毒与宿主之间的相互作用。本研究旨在描述达疟蚊参考基因组中的非逆转录整合 RNA 病毒序列的特征,并鉴定哥伦比亚野外采集蚊子中的推定转录非逆转录整合 RNA 病毒序列。通过与 NCBI 病毒库中以前在节肢动物中鉴定出的所有病毒序列进行 BLAST 查询,分析了达疟蝇参考基因组,以鉴定 NIRVS 并确定其特征。此外,还使用元转录组学方法对现场采集的达疟蚊进行了 NIRVS 检测。结果,在达疟蚊基因组中发现了 44 种 NIRVS,它们构成了来自 Rhabdoviridae、Chuviridae 和 Phasmaviridae 科的阴性单链 RNA 病毒(ssRNA-)的整合,以及来自 Partitiviridae 和 Sedoreoviridae 科的双链 RNA 病毒(dsRNA)的整合。这些 NIRVS 并非随机分布,而是聚集在基因组中富含 BEL/Pao 和 Ty3/Gypsy 长末端重复元件的特定区域。此外,在所有哥伦比亚 An. darlingi 自然种群的转录组数据中都存在类似 NIRVS 的推定序列。这项研究意义重大,因为它首次在新热带地区最重要的疟疾病媒中发现了 NIRVS。研究结果有助于了解蚊子与其病毒组之间错综复杂的关系,以及按蚊属中病毒的调控机制。
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引用次数: 0
Interplay of climate change with physiological changes in adult Aedes albopictus 气候变化与成年白纹伊蚊生理变化的相互作用
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.actatropica.2024.107467
Chinazom Enukoha , Asghar Talbalaghi , Sahar Hassandoust , Fabio Fossati , Marco Bazzoni , Simone Parisato , David Puccioni , Laura Erbetta , Peyman Ghaffari
The effect of unprecedented climate change conditions on the environment has attracted the attention of experts from various disciplines who wish to predict its evolution. This is due to its interaction with population health and people's quality of life. The emergence of vector-borne diseases (VBD) in Europe, particularly caused by invasive mosquitoes, has resulted in autochthonous transmission of Dengue and Chikungunya virus cases. In this contribution, we delve into the significant decline in the population of tiger mosquitoes and the noticeable reduction in their size, related to the changes that occur often in years with low rainfall and high temperatures during the summer months. This change can be traced to the morphology of the species, which has been analysed in this work and related to the possible enhanced transmission efficiency and susceptibility of vectors to VBD dissemination. Due to the greater susceptibility to pathogen replication and subsequent transmission of the pathogens to a host during blood feeding, these morphologically distinct species relatively seem to be an efficient vector. The relationship between the sizes of studied mosquitoes and rainfall levels requires more research by mathematical epidemiologists.
前所未有的气候变化条件对环境的影响引起了各学科专家的关注,他们希望预测气候变化的演变。这是因为气候变化与人口健康和人们的生活质量相互影响。欧洲出现的病媒传染病(VBD),尤其是由入侵蚊子引起的病媒传染病,已经导致登革热和基孔肯雅病毒病例的本土传播。在这篇论文中,我们深入探讨了虎蚊数量的显著下降及其体型的明显缩小,这与夏季降雨量低、气温高的年份经常发生的变化有关。这种变化可以追溯到物种的形态,在这项工作中对其进行了分析,这与传播效率可能提高以及病媒对 VBD 传播的敏感性有关。由于在吸血过程中更容易复制病原体并随后将病原体传播给宿主,这些形态不同的物种似乎相对是一种高效的病媒。所研究的蚊子大小与降雨量之间的关系需要数学流行病学家进行更多的研究。
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引用次数: 0
LarvaeCountAI: a robust convolutional neural network-based tool for accurately counting the larvae of Culex annulirostris mosquitoes. LarvaeCountAI:基于卷积神经网络的鲁棒工具,用于精确计算环纹库蚊的幼虫数量。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.actatropica.2024.107468
Nouman Javed, Adam J López-Denman, Prasad N Paradkar, Asim Bhatti

Accurate counting of mosquito larval populations is essential for maintaining optimal conditions and population control within rearing facilities, assessing disease transmission risks, and implementing effective vector control measures. While existing methods for counting mosquito larvae have faced challenges such as the impact on larval mortality rate, multiple parameters adjustment and limitations in availability and affordability, recent advancements in artificial intelligence, particularly in AI-driven visual analysis, hold promise for addressing these issues. Here, we introduce LarvaeCountAI, an open-source convolutional neural network (CNN)-based tool designed to automatically count Culex annulirostris mosquito larvae from videos captured in laboratory environments. LarvaeCountAI does not require videos to be recorded using an advanced setup; it can count larvae with high accuracy from videos captured using a simple setup mainly consisting of a camera and commonly used plastic trays. Using the videos enables LarvaeCountAI to capitalise on the continuous movement of larvae, enhancing the likelihood of accurately counting a greater number of larvae. LarvaeCountAI adopts a non-invasive approach, where larvae are simply placed in trays and imaged, minimising any potential impact on larval mortality. This approach addresses the limitations associated with previous methods involving mechanical machines, which often increase the risk of larval mortality as larvae pass through multiple sections for counting purposes. The performance of LarvaeCountAI was tested using 10 video samples. Validation results demonstrated the excellent performance of LarvaeCountAI, with an accuracy ranging from 96.25 % to 99.13 % across 10 test videos and an average accuracy of 97.88 %. LarvaeCountAI represents a remarkable advancement in mosquito surveillance technology, offering a robust and efficient solution for monitoring larval populations. LarvaeCountAI can contribute to developing effective strategies for reducing disease transmission and safeguarding public health by providing timely and accurate data on mosquito larvae abundance.

蚊子幼虫数量的精确计数对于保持饲养设施内的最佳条件和数量控制、评估疾病传播风险以及实施有效的病媒控制措施至关重要。虽然现有的蚊子幼虫计数方法面临着一些挑战,如对幼虫死亡率的影响、多参数调整以及可用性和可负担性的限制,但最近人工智能的进步,特别是人工智能驱动的可视化分析,为解决这些问题带来了希望。在此,我们介绍 LarvaeCountAI,这是一种基于卷积神经网络(CNN)的开源工具,旨在从实验室环境中捕获的视频中自动计数库蚊幼虫。LarvaeCountAI 不需要使用高级设置来录制视频;它可以从主要由摄像头和常用塑料托盘组成的简单设置所捕获的视频中对幼虫进行高精度计数。通过视频,LarvaeCountAI 可以利用幼虫的连续运动,提高准确计数更多幼虫的可能性。LarvaeCountAI 采用非侵入式方法,只需将幼虫放入托盘中并进行成像,从而最大限度地降低了对幼虫死亡率的潜在影响。这种方法解决了以往使用机械设备的方法的局限性,因为机械设备往往会增加幼虫死亡的风险,因为幼虫会通过多个部分进行计数。使用 10 个视频样本对 LarvaeCountAI 的性能进行了测试。验证结果表明 LarvaeCountAI 性能卓越,10 个测试视频的准确率从 96.25% 到 99.13%,平均准确率为 97.88%。LarvaeCountAI 代表了蚊虫监测技术的显著进步,为监测幼虫种群提供了强大而高效的解决方案。LarvaeCountAI 能够提供及时准确的蚊子幼虫数量数据,有助于制定有效的战略,减少疾病传播,保障公众健康。
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引用次数: 0
Insights into Leptospira spp. infection in pet cats in Croatia: Clinical, serological and molecular findings with emphasis on the potential important role of serogroup Pomona 洞察克罗地亚宠物猫的钩端螺旋体感染:临床、血清学和分子研究结果,强调波莫纳血清群的潜在重要作用。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.actatropica.2024.107465
Iva Benvin , Daniel Fitz , Vesna Mojčec Perko , Maja Maurić Maljković , Vlasta Đurić , Josipa Habuš , Zrinka Štritof , Matko Perharić , Suzana Hađina , Iva Zečević , Nenad Turk
Leptospirosis, a globally re-emerging zoonosis caused by pathogenic Leptospira spp., poses a significant threat to public health. Leptospirosis in cats is often neglected due to its high underdiagnosis. Therefore, the role of cats in disease transmission and bacterial maintenance in the environment remains unclear. For this study, 54 serum samples, 54 urine samples and 27 EDTA-anticoagulated blood samples from pet cats presenting to the Veterinary Teaching Hospital due to health problems were used. The serum samples were tested for antibodies against 12 pathogenic serovars of Leptospira spp. using the microscopic agglutination test (MAT). EDTA-anticoagulated blood and urine samples were tested for the lipL32 gene of pathogenic Leptospira spp. by conventional (PCR) and real-time (qPCR) polymerase chain reaction. Agglutinating antibodies were detected in 18.52% (10/54) of the sera with a titre range of 1:50 to 1:12800. The most common serogroup was Pomona, followed by Sejroe, Icterohaemorrhagiae, Australis and Javanica. Leptospira spp. DNA was found in 1.85% (1/54) of the urine samples, while all EDTA-anticoagulated blood samples were negative. A statistically significant difference in seropositivity regarding lifestyle was found between outdoor/indoor and indoor-only cats, while the presence of another cat in the household significantly increased the likelihood of seropositivity. Cats with immunocompromising conditions showed a significantly increased risk of seropositivity, especially those undergoing immunosuppressive treatment. In addition, respiratory signs and changes in lung structure associated with the presence of leptospiral antibodies, and these cats were more likely to be infected with the Pomona serogroup. Moreover, cats with anaemia, leucocytosis, and thrombocytopenia were significantly more likely to have antibodies against Leptospira spp., while seropositive cats had significantly lower urine-specific gravity compared to seronegative cats. The results underline the importance of raising awareness of feline leptospirosis in veterinary care and recognising pet cats as potential carriers of leptospires. Further research is needed to clarify the specific role of the Pomona serogroup as a potentially highly evolutionary drifting serogroup in terms of pathogenicity and to clarify the zoonotic potential of infected cats, which is crucial for the implementation of effective public health measures and veterinary interventions.
钩端螺旋体病是由致病性钩端螺旋体属引起的一种全球重新流行的人畜共患疾病,对公共卫生构成严重威胁。由于诊断率低,猫的钩端螺旋体病常常被忽视。因此,猫在疾病传播和细菌维持环境中的作用仍不清楚。本研究采用了 54 份血清样本、54 份尿液样本和 27 份 EDTA 抗凝血样本,这些样本均来自因健康问题前往兽医教学医院就诊的宠物猫。使用显微凝集试验(MAT)检测血清样本中针对 12 种钩端螺旋体病原体血清的抗体。通过常规(PCR)和实时(qPCR)聚合酶链式反应,对经 EDTA 抗凝的血液和尿液样本进行致病性钩端螺旋体 lipL32 基因检测。18.52%(10/54)的血清中检测到凝集抗体,滴度范围为 1:50 至 1:12800。最常见的血清群是 Pomona,其次是 Sejroe、Icterohaemorrhagiae、Australis 和 Javanica。1.85%(1/54)的尿液样本中发现了钩端螺旋体 DNA,而所有 EDTA 抗凝血液样本均为阴性。在生活方式方面,室外/室内猫与纯室内猫的血清阳性率有明显的统计学差异,而家中有另一只猫则会显著增加血清阳性的可能性。免疫力低下的猫血清阳性的风险明显增加,尤其是正在接受免疫抑制治疗的猫。此外,呼吸道症状和肺部结构变化与钩端螺旋体抗体的存在有关,这些猫更有可能感染波莫纳血清群。此外,贫血、白细胞减少和血小板减少的猫明显更容易产生钩端螺旋体抗体,而与血清阴性的猫相比,血清阳性猫的尿液特异性重力明显较低。这些结果强调了在兽医护理中提高对猫钩端螺旋体病的认识以及将宠物猫视为钩端螺旋体潜在携带者的重要性。还需要进一步研究,以明确波莫纳血清群作为潜在的高度进化漂移血清群在致病性方面的具体作用,并明确受感染猫的人畜共患可能性,这对于实施有效的公共卫生措施和兽医干预措施至关重要。
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引用次数: 0
Genetic diversity of Plasmodium vivax population in northeast Myanmar assessed by amplicon sequencing of PvMSP1 and PvMSP3α 通过 PvMSP1 和 PvMSP3α 的扩增子测序评估缅甸东北部间日疟原虫种群的遗传多样性。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.actatropica.2024.107461
Xiaoyuan Wei , Pallavi Malla , Zenglei Wang , Zhaoqing Yang , Yaming Cao , Chengqi Wang , Liwang Cui
This study aimed to assess the baseline genetic diversity of the Plasmodium vivax population in an endemic area of northeast Myanmar at the onset of the malaria elimination campaign in the Greater Mekong Subregion. We genotyped 125 P vivax clinical samples at two merozoite surface protein loci, PvMSP1 and PvMSP3α, by amplicon deep sequencing. Our study revealed that the parasite population in this region was highly diverse, identifying 60 PvMSP1 and 98 PvMSP3α haplotypes, with haplotype diversity of 0.929 and 0.944, respectively. Remarkably, 97.6 % (122/125) of the patients harbored multiclonal infections with a mean multiplicity of infection of 4.18, indicating a relatively high transmission intensity. Neutrality tests and network analysis suggested a recent parasite population expansion, consistent with the concurrent malaria outbreak in the region. These findings underscore the existence of a highly diverse P. vivax population at the China-Myanmar border, highlighting the need for effective malaria control strategies to achieve the goal of regional malaria elimination.
本研究旨在评估大湄公河次区域消除疟疾运动开始时缅甸东北部流行地区间日疟原虫种群的基线遗传多样性。我们通过扩增子深度测序对 125 份间日疟原虫临床样本的两个子虫表面蛋白位点 PvMSP1 和 PvMSP3α 进行了基因分型。我们的研究发现,该区域的寄生虫群体具有高度多样性,共鉴定出 60 个 PvMSP1 和 98 个 PvMSP3α 单倍型,单倍型多样性分别为 0.929 和 0.944。值得注意的是,97.6%(122/125)的患者携带多克隆感染,平均感染倍数为 4.18,表明传播强度相对较高。中性检验和网络分析表明,寄生虫种群最近有所扩大,这与该地区同时爆发的疟疾疫情相一致。这些发现强调了中缅边境存在高度多样化的间日疟原虫种群,突出表明需要采取有效的疟疾控制策略,以实现消除区域疟疾的目标。
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引用次数: 0
Supersaturated drug delivery system of albendazole salt-polymer complex for improving oral bioavailability and efficacy anti-secondary E. multilocularis 阿苯达唑盐-聚合物复合物过饱和给药系统,用于提高口服生物利用度和抗二次多角孢子虫药效
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.actatropica.2024.107464
Chunhui Hu , Xueping Zhong , Chaoqun Li , Haiying Yan
Based on the supersaturation theory, this study devised two albendazole (ABZ) salt-polymer complexes that enhance the oral bioavailability and efficacy of secondary hepatic alveolar echinococcosis (HAE) in rats. Solid characteristics, microstructure, and stability of ABZ benzenesulfonate (ABZ-BSA) and ABZ methanesulfonate (ABZ-MSA) were evaluated. The equilibrium solubility and intrinsic dissolution rate of salt were measured across different pH environments to determine its potential for generating supersaturation. Polymer crystallization inhibitors were subsequently introduced to assess their impact on sustaining supersaturation. The pharmacokinetics and anti-echinococcosis effects of ABZ were evaluated in healthy SD and HAE rats. The characteristic peaks corresponding to amino acid esters and benzimidazole in the ABZ salt structure either shifted or disappeared, corroborated by PXRD, signifying successful ABZ salt preparation. Furthermore, reductions in the melting point and enthalpy of the salts were observed, along with discernible differences in microstructure compared to ABZ. The drug salts exhibited a significant increase in apparent solubility and intrinsic dissolution rate of ABZ, thus laying the groundwork for supersaturation. Stability assessments indicated that salts were susceptible to moisture absorption, necessitating stringent humidity control measures. Notably, HPMC-AS demonstrated promising capabilities in sustaining supersaturation. Finally, pharmacokinetic analyses revealed a substantial increase in the AUC of ABZ-BSA-H and ABZ-MSA-H by 7.6 and 20.3 times, respectively, compared to ABZ in vivo. After a 30-day once-daily oral administration of the Salts and ABZ to SD rats with hepatic alveolar echinococcosis, the ABZ-BSA-H and ABZ-MSA-H formulation demonstrated a cysts inhibition effect 9.2-fold and 15.3-fold greater than that of ABZ. The salt-HPMC-AS complex could potentially be developed into an improved anti-AE drug therapy. Therefore, the salt-HPMC-AS complex could be developed into an enhanced anti-AE drug therapy.
基于过饱和度理论,本研究设计了两种阿苯达唑(ABZ)盐-聚合物复合物,可提高大鼠口服生物利用度和对继发性肝泡棘球蚴病(HAE)的疗效。对 ABZ 苯磺酸盐(ABZ-BSA)和 ABZ 甲磺酸盐(ABZ-MSA)的固体特性、微观结构和稳定性进行了评估。测量了盐在不同 pH 值环境下的平衡溶解度和内在溶解速率,以确定其产生过饱和度的潜力。随后引入了聚合物结晶抑制剂,以评估其对维持过饱和度的影响。在健康的 SD 大鼠和 HAE 大鼠体内评估了 ABZ 的药代动力学和抗包虫病效果。经 PXRD 证实,ABZ 盐结构中与氨基酸酯和苯并咪唑相对应的特征峰发生了移动或消失,这表明 ABZ 盐的制备取得了成功。此外,与 ABZ 相比,盐的熔点和焓都有所降低,微观结构也有明显差异。药物盐明显提高了 ABZ 的表观溶解度和内在溶解速率,从而为过饱和奠定了基础。稳定性评估表明,盐类容易吸潮,因此必须采取严格的湿度控制措施。值得注意的是,HPMC-AS 在维持过饱和方面表现出良好的能力。最后,药代动力学分析表明,与 ABZ 相比,ABZ-BSA-H 和 ABZ-MSA-H 在体内的 AUC 分别大幅增加了 7.6 倍和 20.3 倍。患有肝泡棘球蚴病的 SD 大鼠每天一次口服盐类和 ABZ 30 天后,ABZ-BSA-H 和 ABZ-MSA-H 制剂的囊肿抑制效果分别是 ABZ 的 9.2 倍和 15.3 倍。盐-HPMC-AS复合物有可能发展成为一种改良的抗阿米巴药物疗法。因此,盐-HPMC-AS 复合物可开发成一种增强型抗水痘药物疗法。
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引用次数: 0
Isatin-1,2,3-triazole derivatives: synthesis, molecular docking and evaluation against acute experimental toxoplasmosis. 异汀-1,2,3-三唑衍生物:合成、分子对接和对急性实验性弓形虫病的评估。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.actatropica.2024.107471
Fadwa M Arafa, Nehal Nassef Hezema, Ateyatallah Aljuhani, Mohamed R Aouad, Mohamed Hagar, Ahmed Zakaria, Nadjet Rezki, Marwa M Shaaban, Sara Ahmed Abdel Salam

Toxoplasmosis remains a challenge for both public health and animal husbandry which created a constant demand to develop novel compounds using innovative methods. To join this relentless quest for an ideal chemotherapeutic agent, herein, we developed newly synthesized isatin-1,2,3-triazole derivatives. Three compounds (5a, 5b and 5c) were synthesized, characterized, and loaded on chitosan nanoparticles (CNPs) and then evaluated accordingly. Initially, a molecular docking study was carried out which revealed the effective interaction with the target enzymes; purine nucleoside phosphorylase (PNPase) and T. gondii calcium-dependent protein kinase-1 (TgCDPK1). This was further substantiated by in vivo evaluation of the three compounds (5a-c) and their nanoformulae (5a-CNPs, 5b-CNPs, and 5c-CNPs) against acute Toxoplasma gondii infection in murine model. It is worthy of note that all tested compounds and their nanoformulae produced a significant reduction of parasite burden in both peritoneal fluid and liver impression smear and profound ultrastructural alterations, detected by scanning electron microscopy, compared to the infected non-treated control. The nanoformula 5c-CNPs yielded the most outstanding results with the highest tachyzoite reduction percentage in both peritoneal fluid (98.1%) and liver impression smear (95.3%). Furthermore, the serum levels of liver enzymes (aspartate transaminase (AST) and alanine transaminase (ALT), and renal function tests (urea and creatinine) in mice were within normal limits which makes them more appealing candidates with proven safety. To the best of our knowledge, the present work is the first in silico and in vivo study proving the anti-Toxoplasma effect of isatin-1,2,3- triazoles which paves the way for further development of isatin and triazole-based leads for the treatment of toxoplasmosis.

弓形虫病仍然是公共卫生和畜牧业面临的一项挑战,这就要求我们不断采用创新方法开发新型化合物。为了加入对理想化疗药物的不懈追求,我们在此开发了新合成的异atin-1,2,3-三唑衍生物。我们对三种化合物(5a、5b 和 5c)进行了合成、表征,并将其载入壳聚糖纳米颗粒(CNPs),然后进行了相应的评估。首先进行了分子对接研究,结果表明该化合物与目标酶(嘌呤核苷磷酸化酶(PNPase)和淋球菌钙依赖性蛋白激酶-1(TgCDPK1))之间存在有效的相互作用。对三种化合物(5a-c)及其纳米复合物(5a-CNPs、5b-CNPs 和 5c-CNPs)在小鼠模型中抗弓形虫急性感染的体内评估进一步证实了这一点。值得注意的是,与未受感染的对照组相比,所有受试化合物及其纳米配方都能显著减少腹腔液和肝脏涂片中的寄生虫数量,并通过扫描电子显微镜检测到严重的超微结构改变。纳米制剂 5c-CNPs 的效果最为显著,在腹腔液(98.1%)和肝脏印模涂片(95.3%)中的速生虫减少率最高。此外,小鼠血清中的肝酶(天门冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT))水平以及肾功能检测(尿素和肌酐)均在正常范围内,这使它们成为更有吸引力的安全候选药物。据我们所知,本研究是第一项证明异汀-1,2,3-三唑抗弓形虫作用的硅学和体内研究,为进一步开发异汀和三唑类治疗弓形虫病的新药铺平了道路。
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Acta tropica
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