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Wolbachia-based emerging strategies for control of vector-transmitted disease 基于 Wolbachia 的控制病媒传播疾病的新策略。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-28 DOI: 10.1016/j.actatropica.2024.107410
Diego Montenegro , Gerardo Cortés-Cortés , María Guadalupe Balbuena-Alonso , Caison Warner , Manel Camps
Dengue fever is a mosquito-transmitted disease of great public health importance. Dengue lacks adequate vaccine protection and insecticide-based methods of mosquito control are proving increasingly ineffective. Here we review the emerging use of mosquitoes transinfected with the obligate intracellular bacterium Wolbachia pipientis for vector control. Wolbachia often induces cytoplasmic incompatibility in its mosquito hosts, resulting in infertile progeny between an infected male and an uninfected female. Wolbachia infection also suppresses the replication of pathogens in the mosquito, a process known as “pathogen blocking”. Two strategies have emerged. The first one releases Wolbachia carriers (both male and female) to replace the wild mosquito population, a process driven by cytoplasmic incompatibility and that becomes irreversible once a threshold is reached. This suppresses disease transmission mainly by pathogen blocking and frequently requires a single intervention. The second strategy floods the field population with an exclusively male population of Wolbachia-carrying mosquitoes to generate infertile hybrid progeny. In this case, transmission suppression depends largely on decreasing the population density of mosquitoes driven by infertility and requires continued mosquito release. The efficacy of both Wolbachia-based approaches has been conclusively demonstrated by randomized and non-randomized studies of deployments across the world. However, results conducted in one setting cannot be directly or easily extrapolated to other settings because dengue incidence is highly affected by the conditions into which the mosquitoes are released. Compared to traditional vector control methods, Wolbachia-based approaches are much more environmentally friendly and can be effective in the medium/long term. On the flip side, they are much more complex and cost-intensive operations, requiring a substantial investment, infrastructure, trained personnel, coordination between agencies, and community engagement. Finally, we discuss recent evidence suggesting that the release of Wolbachia-transinfected mosquitoes has a moderate potential risk of spreading potentially dangerous genes in the environment.
登革热是一种由蚊子传播的疾病,对公共卫生具有重大意义。登革热缺乏足够的疫苗保护,以杀虫剂为基础的灭蚊方法也越来越无效。在此,我们回顾了新出现的利用转染了琵琶虫Wolbachia的蚊子来控制病媒的方法。沃尔巴克氏菌通常会诱导蚊子宿主的细胞质不相容,导致受感染的雄蚊和未受感染的雌蚊产生不能生育的后代。沃尔巴克氏体感染还能抑制病原体在蚊子体内的复制,这一过程被称为 "病原体阻断"。目前出现了两种策略。第一种是释放沃尔巴克氏体携带者(包括雄蚊和雌蚊)来取代野生蚊子种群,这一过程由细胞质不相容驱动,一旦达到临界值就不可逆转。这主要是通过病原体阻断来抑制疾病传播,通常只需要一次干预。第二种策略是用携带沃尔巴克氏体的纯雄性蚊子淹没野外种群,以产生不能生育的杂交后代。在这种情况下,抑制传播主要取决于降低因不育造成的蚊子种群密度,需要持续释放蚊子。这两种基于沃尔巴克氏体的方法的有效性已通过在世界各地部署的随机和非随机研究得到确证。然而,由于登革热发病率受蚊子释放环境的影响很大,因此在一种环境下取得的结果不能直接或轻易地推断到其他环境。与传统方法相比,基于沃尔巴克氏体的方法更环保,而且在中长期内有效。但另一方面,这些方法也更加复杂,需要大量的投资、基础设施、训练有素的人员、机构间的协调以及社区的参与。最后,我们讨论了最近的证据,这些证据表明,释放的蚊子中转染的沃尔巴克氏体具有在环境中传播基因的中等潜在风险。
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引用次数: 0
Identification and functional validation of P450 genes associated with pyrethroid resistance in the malaria vector Anopheles sinensis (Diptera Culicidae) 疟疾病媒中华按蚊(双翅目疟蚊科)中与拟除虫菊酯抗性有关的 P450 基因的鉴定和功能验证。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-27 DOI: 10.1016/j.actatropica.2024.107413
Ying-Ao Guo, Feng-Ling Si, Bao-Zhu Han, Liang Qiao, Bin Chen
Cytochrome P450 monooxygenases (P450s), a multifunctional protein superfamily, are one of three major classes of detoxification enzymes. However, the diversity and functions of P450 genes from pyrethroid-resistant populations of Anopheles sinensis have not been fully explored. In this study, P450 genes associated with pyrethroid resistance were systematically screened using RNA-seq in three field pyrethroid-resistant populations (AH-FR, CQ-FR, YN-FR) and one laboratory resistant strain (WX-LR) at developmental stages, tissues, and post blood-meal in comparison to the laboratory susceptible strain (WX-LS) in An. sinensis. Importantly, the expression of significantly upregulated P450s was verified using RT-qPCR, and the function of selected P450s in pyrethroid detoxification was determined with RNA interference using four laboratory pyrethroid-resistant strains (WX-LR, AH-LR, CQ-LR, YN-LR). Sixteen P450 genes were significantly upregulated in at least one field-resistant population, and 44 were significantly upregulated in different developmental stages, tissues or post blood-meal. A total of 19 P450s were selected to verify their association with pyrethroid resistance, and four of them (AsCYP6P3v1, AsCYP6P3v2, AsCYP9J10, and AsCYP9K1) demonstrated significant upregulation in laboratory pyrethroid-resistant strains using RT-qPCR. Knockdown of these four genes all significantly reduced pyrethroid resistance and increased the mortality by 57.19% (AsCYP6P3v1 and AsCYP6P3v2 knockdown group), 38.39% (AsCYP9K1 knockdown group) and 48.87% (AsCYP9J10 knockdown group) in An. sinensis by RNAi, which determined the pyrethroid detoxification function of these four genes. This study revealed the diversity of P450 genes and provided functional evidence for four P450s in pyrethroid detoxification in An. sinensis for the first time, which increases our understanding of the pyrethroid resistance mechanism, and is of potential value for pyrethroid resistance detection and surveillance.
细胞色素 P450 单氧化酶(P450s)是一个多功能蛋白质超家族,是三大类解毒酶之一。然而,对拟除虫菊酯抗性的中华按蚊种群中的 P450 基因的多样性和功能尚未进行充分的研究。本研究利用RNA-seq技术系统地筛选了三个野外除虫菊酯抗性种群(AH-FR、CQ-FR、YN-FR)和一个实验室抗性株系(WX-LR)在发育阶段、组织和血餐后与实验室易感株系(WX-LS)相比与除虫菊酯抗性相关的P450基因。重要的是,利用 RT-qPCR 验证了明显上调的 P450s 的表达,并利用四个实验室除虫菊酯抗性菌株(WX-LR、AH-LR、CQ-LR、YN-LR),通过 RNA 干扰确定了所选 P450s 在除虫菊酯解毒中的功能。在至少一个田间抗性种群中,有 16 个 P450 基因明显上调,在不同发育阶段、组织或血餐后,有 44 个基因明显上调。利用 RT-qPCR 技术,共选择了 19 个 P450 基因来验证它们与拟除虫菊酯抗性的关系,其中四个基因(AsCYP6P3v1、AsCYP6P3v2、AsCYP9J10 和 AsCYP9K1)在实验室拟除虫菊酯抗性菌株中表现出明显的上调。通过RNAi方法,敲除这四个基因均能显著降低拟除虫菊酯抗性,并使中华鳖的死亡率增加57.19%(AsCYP6P3v1和AsCYP6P3v2基因敲除组)、38.39%(AsCYP9K1基因敲除组)和48.87%(AsCYP9J10基因敲除组),从而确定了这四个基因的拟除虫菊酯解毒功能。该研究首次揭示了P450基因的多样性,并提供了4个P450在中华蚁除虫菊酯解毒过程中的功能证据,加深了我们对除虫菊酯抗性机理的认识,对除虫菊酯抗性检测和监控具有潜在价值。
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引用次数: 0
Tick-borne pathogens in Mongolian ticks: The high prevalence of Rickettsia raoultii and its public health implications 蒙古蜱虫中的蜱媒病原体:Rickettsia raoultii 的高流行率及其对公共卫生的影响。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-26 DOI: 10.1016/j.actatropica.2024.107412
You-Jeong Lee , Beoul Kim , Dongmi Kwak , Ochirkhuu Nyamsuren , Nyamdavaa Guugandaa , Min-Goo Seo
In Mongolia, a substantial segment of the population is engaged in pastoralism, leading to frequent interactions with livestock and heightened exposure to tick-infested environments. Consequently, ticks and the endemic tick-borne pathogens (TBPs) they harbor present significant health threats. In May 2021, we conducted a study to evaluate the prevalence of 9 TBPs in ticks collected from four regions in Mongolia: Uvurkhangai, Tuv, Bayan-Ulgii, and Khentii. The pathogens surveyed included Anaplasma, Rickettsia, Bartonella, Borrelia, Ehrlichia, Babesia, Toxoplasma, Theileria, and lumpy skin disease virus. Molecular analysis of 1142 ticks revealed that, although the majority of TBPs were not detected, 89.1 % of the ticks were positive for Rickettsia. Genetic characterization using the 16S rRNA and gltA genes identified the pathogen identified the pathogen Rickettsia raoultii. Species identification indicated a predominance of Dermacentor nuttalli (70.0 %) and Dermacentor silvarum (30.0 %). These findings highlight the extensive prevalence of R. raoultii in Mongolia and underscore the urgent need for heightened awareness and preventive measures due to the high level of interaction between livestock and humans. The genetic similarity of R. raoultii sequences to those found in neighboring countries suggests potential cross-border transmission, underscoring the importance of conducting similar research in surrounding regions. This study advances our understanding of the epidemiology of tick-borne diseases in Mongolia and can inform public health strategies aimed at mitigating the risks associated with these infections.
在蒙古,很大一部分人口从事畜牧业,因此经常与牲畜打交道,也更容易接触到蜱虫肆虐的环境。因此,蜱虫及其携带的地方性蜱媒病原体(TBPs)对健康构成了严重威胁。2021 年 5 月,我们进行了一项研究,评估从蒙古四个地区采集的蜱虫中 9 种 TBPs 的流行情况:我们在 2021 年 5 月进行了一项研究,评估了从蒙古乌武尔汗盖、图瓦、巴彦乌勒盖和肯特伊四个地区采集的蜱虫中 9 种 TBP 的流行情况。调查的病原体包括阿纳普拉丝虫、立克次体、巴顿氏菌、鲍氏菌、埃立克次氏体、巴贝斯虫、弓形虫、毛癣菌和块状皮肤病病毒。对 1142 只蜱进行的分子分析表明,虽然没有检测到大多数 TBPs,但 89.1%的蜱对立克次体呈阳性。利用 16S rRNA 和 gltA 基因进行的基因鉴定确定了病原体为 Rickettsia raoultii。物种鉴定表明,主要是 Dermacentor nuttalli(70.0%)和 Dermacentor silvarum(30.0%)。这些发现凸显了 R. raoultii 在蒙古的广泛流行,并强调由于牲畜与人类的高度互动,迫切需要提高意识和采取预防措施。R.raoultii序列与邻国发现的R.raoultii序列的遗传相似性表明可能存在跨境传播,这突出了在周边地区开展类似研究的重要性。这项研究加深了我们对蒙古蜱传疾病流行病学的了解,并可为旨在降低这些传染病相关风险的公共卫生策略提供信息。
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引用次数: 0
Nation-wide surveillance of ticks (Acari: Ixodidae) on birds in Singapore 新加坡全国鸟类蜱虫(Acari: Ixodidae)监测。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-26 DOI: 10.1016/j.actatropica.2024.107411
Mackenzie L. Kwak , Leshon Lee , David J.X. Tan , Frank E. Rheindt , Ryo Nakao
Surveillance programs focused on bird ticks are often challenging owing to the difficulty in capturing and screening birds as well as the fact that ticks on avian hosts frequently occur at a low prevalence. Nonetheless, elucidating the diversity and host preferences of avian ticks is critical for understanding public health risks posed by both migratory and resident birds. The first nation-wide surveillance program of avian ticks was initiated to examine bird-tick interactions in Singapore, a key juncture along the East Asian–Australasian flyway. Two tick species were detected, namely Haemaphysalis wellingtoni and Rhipicephalus linnaei, while five bird species were found to host ticks in Singapore, namely Columba livia, Gallus gallus, Ixobrychus flavicollis, Lanius cristatus, and Pitta moluccensis. The threats posed to public health by the human-biting tick H. wellingtoni are discussed along with the potential for migratory birds and ticks to transport tick-borne pathogens into, and through, Singapore.
由于难以捕捉和筛查鸟类,而且鸟类宿主身上的蜱虫经常以较低的流行率出现,因此以鸟类蜱虫为重点的监测计划往往具有挑战性。然而,阐明鸟类蜱虫的多样性和宿主偏好对于了解候鸟和留鸟带来的公共卫生风险至关重要。新加坡是东亚-澳大利西亚飞行路线上的一个重要节点,为了研究鸟类与蜱虫之间的相互作用,新加坡启动了首个全国性的禽蜱监测计划。在新加坡发现了两种蜱虫,分别是Haemaphysalis wellingtoni和Rhipicephalus linnaei,而有五种鸟类寄生了蜱虫,分别是Columba livia、Gallus gallus、Ixobrychus flavicollis、Lanius cristatus和Pitta moluccensis。本文讨论了人咬蜱H. wellingtoni对公共卫生造成的威胁,以及候鸟和蜱虫将蜱传病原体传播到新加坡或通过新加坡传播的可能性。
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引用次数: 0
Incriminating leishmaniases vectors in Colombia: An overview and roadmap for future research 哥伦比亚的利什曼病病媒:概述和未来研究路线图
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-22 DOI: 10.1016/j.actatropica.2024.107409
Laura Posada-Lopez , Eunice AB Galati , Jeffrey Shaw , Fredy Galvis-Ovallos
A major challenge in defining the vector status of phlebotomine sand flies is selecting the appropriate criteria. Vectors can be graded by importance, with successful transmission as the highest grade. Potential vectors are often identified based on high frequency in transmission foci, anthropophily, and more recently by identification of DNA in field samples. However, a species' ability to transmit a pathogen depends not only on its intrinsic biology of sand fly–Leishmania interactions but also on ecological parameters, which are rarely evaluated. This study aimed to analyze the literature data describing characteristics of Colombian sand flies related to their role as vectors of Leishmaniinae parasites. Based on information contained in scientific publications using combinations of five criteria, sand fly species were graded into five levels, and 26 species were considered as potential or proven leishmaniasis vectors in Colombia. Levels one to four refer to potential or suspected status, while level five denotes proven vectors. Studying vectors in a regional context is crucial because species' behaviors vary with environmental and ecological conditions, meaning a species may be a key vector in one area but not in another. A better understanding of vector-parasite interactions will aid in developing innovative control strategies and formulating significant epidemiological perspectives.
确定血吸虫沙蝇病媒状况的一个主要挑战是选择适当的标准。病媒可按重要性分级,成功传播为最高级别。潜在的病媒通常是根据在传播地的高频率、嗜人性,以及最近通过对野外样本中 DNA 的鉴定来确定的。然而,一个物种传播病原体的能力不仅取决于沙蝇与利什曼原虫相互作用的内在生物学特性,还取决于生态学参数,而这些参数很少得到评估。本研究旨在分析描述哥伦比亚沙蝇作为利什曼伊科寄生虫传播媒介的特征的文献数据。根据科学出版物中包含的信息,结合五项标准,将沙蝇物种分为五个等级,并将 26 个物种视为哥伦比亚利什曼病的潜在或已证实病媒。一至四级为潜在或疑似病媒,五级为已证实病媒。在区域背景下研究病媒至关重要,因为物种的行为会随着环境和生态条件的变化而变化,这意味着一个物种可能在一个地区是主要病媒,但在另一个地区却不是。更好地了解病媒与寄生虫之间的相互作用将有助于制定创新的控制策略和形成重要的流行病学观点。
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引用次数: 0
Diversity, vertical stratification and detection of Leishmania DNA in sand flies (Diptera: Psychodidae) collected in the Mapinguari National Park, Brazilian Amazon 在巴西亚马逊马宾加里国家公园采集的沙蝇(双翅目:灵蝇科)的多样性、垂直分层和利什曼病 DNA 检测。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-19 DOI: 10.1016/j.actatropica.2024.107407
Linda Kimberlin dos Santos Teles Oliveira , Michelli Santos da Silva , Tivian Raphaella Melo Munis , Gabriel Moreira Valença , Kamila Pereira de França , Janaina Danielle Alves , Antônio Marques Pereira Júnior , Priscilla Elias Ferreira da Silva , Jansen Fernandes Medeiros
This study aimed to assess the diversity patterns of sand fly fauna across different strata and detect Leishmania DNA in these insects in the Mapinguari National Park in Rondônia and Amazonas states, Northern Brazil. Sand flies were collected with “HP” light traps in the canopy (15 m) and at ground level (1 m) on two trails, during August and November 2021 and March and August 2022. Polymerase chain reaction and DNA sequencing were used to identify Leishmania species. A total of 8,040 individuals (2,303♂ – 28.64 %, 5,737♀ – 71.36 %) were collected and 53 species and 13 genera were identified. The most abundant species were Psychodopygus chagasi (21.00 %), Trichophoromyia ubiquitalis (13.61 %) Psychodopygus davisi (11.69 %), Nyssomyia fraihai (10.58 %), Nyssomyia antunesi (6.68 %) and Nyssomyia richardwardi (5.55 %). Species diversity was greater in the canopy (Shannon index H' = 10.8 common species) when compared to ground level (H' = 10.5 common species). We observed a minimum infection rate of 0.45 % (22/4,868 females), in which Leishmania braziliensis DNA was found in Ps. chagasi and Le. lainsoni DNA in Ps. chagasi, Ny. richardwardi, Ps. ayrozai and Th. ubiquitalis. The minimum infection rate of Leishmania in the canopy was 0.47 % (19/4,031) and in the ground was 0.52 % (3/567). In the present study, we observed Le. lainsoni DNA in females of Ny. richardwardi for the first time. The data presented in this study contribute to understanding sand fly diversity and its distribution between the states of Rondônia and Amazonas. They may be useful for implementing targeted control measures to reduce the spread of leishmaniasis and implement entomological surveillance strategies.
本研究旨在评估巴西北部朗多尼亚州和亚马孙州马宾加里国家公园不同地层沙蝇动物群的多样性模式,并检测这些昆虫体内的利什曼病DNA。在 2021 年 8 月和 11 月以及 2022 年 3 月和 8 月期间,使用 "HP "灯光诱捕器在两条路径上的树冠(15 米)和地面(1 米)收集沙蝇。聚合酶链式反应和 DNA 测序被用来鉴定利什曼原虫的种类。共采集到 8 040 个个体(2 303♂ - 28.64%,5 737♀ - 71.36%),鉴定出 53 个种和 13 个属。数量最多的物种为 Psychodopygus chagasi(21.00%)、Trichophoromyia ubiquitalis(13.61%)、Psychodopygus davisi(11.69%)、Nyssomyia fraihai(10.58%)、Nyssomyia antunesi(6.68%)和 Nyssomyia richardwardi(5.55%)。树冠层的物种多样性(香农指数 H' = 10.8 种常见物种)高于地面层(H' = 10.5 种常见物种)。我们观察到最低感染率为 0.45%(22/4,868 只雌虫),其中在 Ps. chagasi 中发现了巴西利什曼病 DNA,在 Ps. chagasi、Ny. richardwardi、Ps. ayrozai 和 Th. ubiquitalis 中发现了莱什曼尼亚属 DNA。利什曼原虫在树冠上的最低感染率为 0.47%(19/4,031),在地面上的最低感染率为 0.52%(3/567)。在本研究中,我们首次在 Ny. richardwardi 的雌性体内观察到了 Le. lainsoni DNA。本研究提供的数据有助于了解沙蝇的多样性及其在朗多尼亚州和亚马孙州之间的分布情况。这些数据可能有助于实施有针对性的控制措施,以减少利什曼病的传播,并有助于实施昆虫学监测策略。
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引用次数: 0
Corrigendum to: "Surveillance and control of Trypanosoma evansi in the canary Islands: A descriptive analysis" [Acta Tropica, 246 (2023), 106990]. 更正:"加那利群岛对伊万斯锥虫的监测和控制:描述性分析》[《热带学报》,246 (2023),106990]:A descriptive analysis" [Acta Tropica, 246 (2023), 106990]。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-17 DOI: 10.1016/j.actatropica.2024.107390
María Teresa Tejedor-Junco, Adrián Melián Henríquez, Pedro Peláez Puerto, María Dolores Ramos, Margarita González-Martín, Manuel Morales Doreste, Geoffrey Gimonneau, Marc Desquesnes, Sergio Martín Martel, Juan Alberto Corbera
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引用次数: 0
Managing vector-borne diseases in a geoAI-enabled society. Malaria as an example 在地理信息系统支持的社会中管理病媒传染的疾病。以疟疾为例。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-17 DOI: 10.1016/j.actatropica.2024.107406
Justine I Blanford
More than 17 % of all infectious diseases are caused by vector-borne diseases resulting in more than 1 billion cases and over 1 million deaths each year. Of these malaria continues to be a global burden in over eighty countries. As societies become more digitalised, the availability of geospatially enabled health and disease information will become more abundant. With this, the ability to assess health and disease risks in real-time will become a reality.
The purpose of this study was to examine how geographic information, geospatial technologies and spatial data science are being used to reduce the burden of vector-borne diseases such as malaria and explore the opportunities that lie ahead with GeoAI and other geospatial technology advancements.
Malaria is a dynamic and complex system and as such a range of data and approaches are needed to tackle different parts of the malaria cycle at different local and global scales. Geospatial technologies provide an integrated framework vital for monitoring, analysing and managing vector-borne diseases. GeoAI and technological advancements are useful for enhancing real-time assessments, accelerating the decision making process and spatial targeting of interventions. Training is needed to enhance the use of geospatial information for the management of vector-borne diseases.
在所有传染病中,17%以上是由病媒传播的疾病引起的,每年造成 10 亿多病例和 100 多万人死亡。其中,疟疾仍然是全球 80 多个国家的负担。随着社会日益数字化,地理空间支持的健康和疾病信息将更加丰富。因此,实时评估健康和疾病风险的能力将成为现实。本研究旨在探讨如何利用地理信息、地理空间技术和空间数据科学来减轻疟疾等病媒传播疾病的负担,并探索 GeoAI 和其他地理空间技术进步所带来的机遇。疟疾是一个动态而复杂的系统,因此需要一系列数据和方法来处理不同地方和全球范围内疟疾周期的不同部分。地理空间技术提供了一个对监测、分析和管理病媒传染疾病至关重要的综合框架。GeoAI 和技术进步有助于加强实时评估、加快决策进程和干预措施的空间定位。需要开展培训,以加强地理空间信息在病媒传播疾病管理中的应用。
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引用次数: 0
Up-regulation of MDSCs accumulation and Th2 biased response to co-stimulation of CsESP from Clonorchis sinensis and HBeAg in vitro 中华皂苷和 HBeAg 共同刺激体外 MDSCs 积累和 Th2 偏向反应的上调作用
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-15 DOI: 10.1016/j.actatropica.2024.107405
Qiannan Liu , Nian Wang , Hengchang Sun , Huimin Dong , Xuerong Li , Xinbing Yu , Yan Huang

Co-infection with Clonorchis sinensis (C. sinensis) and Hepatitis B virus (HBV) are commonly observed in endemic areas of Clonorchiasis. Chronic infection of C. sinensis or HBV is more likely to happen. However, the immune mechanisms related to the pathogenesis of co-infection remain unknown. In the present study, Myeloid-derived suppressor cells (MDSCs) accumulation, bone marrow derived dendritic cells (BMDCs) reaction and the consequent effectors on Th1/Th2 polarization to co-incubation of excretory-secretory products from C. sinensis (CsESP) and Hepatitis B e antigen (HBeAg) in vitro were investigated for further understanding the immune response during co-infection. The results indicated that compared with CsESP or HBeAg alone, co-stimulation dominantly promoted MDSCs accumulation. Co-stimulation significantly downregulated the expression of CD80 and CD86, and reduced IL-12p70 release while augmented IL-10 levels of BMDCs. Higher transcription levels of mannose receptor (MR) while lower mRNA level of toll like receptor 4 (TLR-4) were detected among membrane receptors of BMDCs with co-treatment. In addition, after CD4 naïve T cells were stimulated by LPS-treated BMDCs with CsESP and HBeAg, the proportion of CD4+IL-4+ T cells and IL-4 increased, while CD4+INF-γ+ T cells percentage and INF-γ down-regulated. In conclusion, CsESP and HBeAg co-incubation more distinctly suppressed maturation of BMDCs resulting in increase of IL-10 and decrease of IL-12 highly possible by up-regulation of MR and down-regulation of TLR-4 of BMDCs, and successively induce Th2 immune skewing. These findings laid the cornerstone to further clarify immune responses during the co-infection contributing to the better precise treatment and progression assessment of co-infection patients.

在中华蟠尾丝虫病流行地区,常见中华蟠尾丝虫(C. sinensis)和乙型肝炎病毒(HBV)的合并感染。慢性感染中华癣菌或 HBV 的可能性更大。然而,与合并感染的发病机制有关的免疫机制仍然未知。在本研究中,为了进一步了解共同感染过程中的免疫反应,研究人员在体外研究了髓源性抑制细胞(MDSCs)的积累、骨髓树突状细胞(BMDCs)的反应以及由此产生的Th1/Th2极化效应对中华睾吸虫(CsESP)和乙型肝炎e抗原(HBeAg)共同作用的影响。结果表明,与单独使用 CsESP 或 HBeAg 相比,联合刺激能显著促进 MDSCs 的聚集。共同刺激可明显下调 CD80 和 CD86 的表达,减少 IL-12p70 的释放,同时提高 BMDCs 的 IL-10 水平。在联合刺激下,BMDCs 的膜受体中甘露糖受体(MR)的转录水平升高,而类毒素受体 4(TLR-4)的 mRNA 水平降低。此外,经 CsESP 和 HBeAg 与 LPS 处理的 BMDCs 刺激 CD4 天真 T 细胞后,CD4+IL-4+ T 细胞比例和 IL-4 增加,而 CD4+INF-γ+ T 细胞比例和 INF-γ 下调。总之,CsESP 和 HBeAg 共孵育更明显地抑制了 BMDCs 的成熟,导致 IL-10 的增加和 IL-12 的减少,这高度可能是通过上调 BMDCs 的 MR 和下调 TLR-4 实现的,并先后诱导 Th2 免疫倾斜。这些发现为进一步阐明合并感染期间的免疫反应奠定了基础,有助于对合并感染患者进行更精确的治疗和病情进展评估。
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引用次数: 0
Low-cost and simple PCR process for access to molecular diagnosis of HTLV-1/2 in low-resource countries 低成本、简便的 PCR 流程,可用于低资源国家的 Htlv-1/2 分子诊断。
IF 2.1 3区 医学 Q2 PARASITOLOGY Pub Date : 2024-09-14 DOI: 10.1016/j.actatropica.2024.107395
Nicolás Ducasa , Diego Domínguez , Paula Benencio , Laura Alfie , Patricia Etcheves , Giampaolo Scarton , Mirna Biglione , Mariela Caputo

Background

HTLV-1/2 exhibit a widespread distribution globally and are associated with severe clinical manifestations, necessitating precise viral identification for diagnosis. Currently, there are no official diagnostic guidelines, and a variety of published protocols exists. We introduce an enhanced nested real-time PCR technique followed by high-resolution melting (rtPCR-HRM), designed to offer a cost-effective and straightforward tool for the simultaneous identification of both viruses.

Methods

The technique was tested in a retrospective, blinded study, involving a total panel of 110 samples, of which 47 were positive for HTLV-1, 12 for HTLV-2, and 51 tested negatives. Additionally, we compared the performance of this technique with a line immunoassay (LIA).

Results

The results demonstrate 100 % sensitivity, specificity, and diagnostic accuracy for both viruses. Sensitivity analysis indicated that at least 1 viral copy of HTLV-1 and 14.4 viral copies of HTLV-2 could be reliably detected.

Conclusions

Our results indicate that rtPCR-HRM is effective in confirming HTLV-1 and HTLV-2 infection, important in Latin American countries where both viruses circulate. Furthermore, the proposed strategy provides a new tool that can be used to resolve indeterminate cases identified by Western blot, with the added advantage of being faster and simpler than n-PCR and more cost-effective than other probe-based RT-PCRs.
背景:HTLV-1/2 在全球广泛分布,并伴有严重的临床表现,因此需要进行精确的病毒鉴定以进行诊断。目前,尚无官方诊断指南,已公布的方案也多种多样。我们介绍了一种增强型巢式实时 PCR 技术和高分辨率熔解技术(rtPCR-HRM),旨在为同时鉴定这两种病毒提供一种经济高效的直接工具:在一项回顾性盲法研究中对该技术进行了测试,共检测了 110 份样本,其中 47 份样本检测结果为 HTLV-1 阳性,12 份样本检测结果为 HTLV-2 阳性,51 份样本检测结果为阴性。此外,我们还比较了该技术与线性免疫测定(LIA)的性能:结果:结果表明,对这两种病毒的敏感性、特异性和诊断准确性均为 100%。灵敏度分析表明,至少可以可靠地检测出 1 个 HTLV-1 病毒拷贝和 14.4 个 HTLV-2 病毒拷贝:我们的研究结果表明,rtPCR-HRM 能有效确诊 HTLV-1 和 HTLV-2 感染,这在两种病毒均有流行的拉丁美洲国家非常重要。此外,所提出的策略还提供了一种新工具,可用于解决 Western 印迹鉴定出的不确定病例,其额外优势是比 n-PCR 更快、更简单,比其他基于探针的 RT-PCR 更具成本效益。
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Acta tropica
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