Pub Date : 2024-08-10DOI: 10.1016/j.ttbdis.2024.102386
C. Ndawula Jr , P. Emudong , N. Muwereza , C. Currà
Instead of using the Infection and Treatment Method (ITM)-based vaccine, is it possible to control East Coast Fever (ECF) through blocking Theileria parva transmission in ticks and cattle? This review pursues this question. It's over 100 years since Arnold Theiler (1912) first illustrated the natural ITM as a vaccination approach against ECF-cattle disease. The approach entails infecting cattle with live Theileria sporozoites and co-treatment with long-acting tetracycline. Building on the ITM principle, the “Muguga”-cocktail ECF vaccine was developed in the 1970s and it remains the only commercially available-one. Although the vaccine induces cattle-protection, the vaccination approach still raises several drawbacks. Of those, the most outstanding is the vaccine-safety. This is implied because after ITM vaccination, cattle revert to T. parva pathogen reservoirs, therefore, during blood meal-acquisition, the ticks co-ingest T. parva pathogens. Ultimately, the pathogens are further transmitted transstadial; from larvae to nymph and nymph-adults and later re-transmitted to cattle during blood-meal acquisition. Consequently, the vaccine-constituting T. parva strains are introduced and (re) spread in non-endemic/ endemic areas. Precisely, rather than eradicating the disease, the ITM vaccination-approach promotes ECF endemicity. With advent of novel vaccination approaches toward vector and vector-borne disease control, ECF-control based on ITM of vaccination is considered outdated. The review highlights the need for embracing a holistic integrative vaccination approach entailing blocking Theileria pathogen-development and transmission both in the ticks and cattle, and/or the tick-population.
是否有可能不使用基于感染和治疗方法 (ITM) 的疫苗,而是通过阻断副疟原虫在蜱和牛中的传播来控制东海岸热 (ECF)?本综述将探讨这一问题。自 Arnold Theiler(1912 年)首次将自然 ITM 作为预防东海岸热-牛病的疫苗接种方法以来,已有 100 多年的历史。这种方法需要用活的泰勒氏孢子虫感染牛,并同时使用长效四环素进行治疗。在 ITM 原理的基础上,20 世纪 70 年代开发出了 "Muguga"-鸡尾 ECF 疫苗,目前仍是唯一可在市场上买到的疫苗。虽然这种疫苗能对牛起到保护作用,但疫苗接种方法仍存在一些缺陷。其中最突出的是疫苗安全性。这是因为在接种 ITM 疫苗后,牛会变回 T. parva 病原体储库,因此,在血餐采集过程中,蜱会与 T. parva 病原体共存。最终,病原体进一步经体表传播;从幼虫到若虫和若虫-成虫,然后在获取血餐时再次传播给牛。因此,在非地方病/地方病流行地区,疫苗构成的 T. parva 菌株被引入并(再次)传播。准确地说,ITM 疫苗接种方法非但没有根除疾病,反而助长了 ECF 的流行。随着控制病媒和病媒传播疾病的新型疫苗接种方法的出现,基于ITM疫苗接种的ECF控制被认为已经过时。这篇综述强调了采用整体综合疫苗接种方法的必要性,这种方法需要同时阻止蜱和牛体内的毛癣菌病原体发展和传播,以及/或阻止蜱群的发展和传播。
{"title":"Insights into Theileria transmission-blocking vaccines for East Coast fever control: A disease with an “outdated vaccination approach”","authors":"C. Ndawula Jr , P. Emudong , N. Muwereza , C. Currà","doi":"10.1016/j.ttbdis.2024.102386","DOIUrl":"10.1016/j.ttbdis.2024.102386","url":null,"abstract":"<div><p>Instead of using the Infection and Treatment Method (ITM)-based vaccine, is it possible to control East Coast Fever (ECF) through blocking <em>Theileria parva</em> transmission in ticks and cattle? This review pursues this question. It's over 100 years since Arnold Theiler (1912) first illustrated the natural ITM as a vaccination approach against ECF-cattle disease. The approach entails infecting cattle with live <em>Theileria</em> sporozoites and co-treatment with long-acting tetracycline. Building on the ITM principle, the “Muguga”-cocktail ECF vaccine was developed in the 1970s and it remains the only commercially available-one. Although the vaccine induces cattle-protection, the vaccination approach still raises several drawbacks. Of those, the most outstanding is the vaccine-safety. This is implied because after ITM vaccination, cattle revert to <em>T. parva</em> pathogen reservoirs, therefore, during blood meal-acquisition, the ticks co-ingest <em>T. parva</em> pathogens. Ultimately, the pathogens are further transmitted transstadial; from larvae to nymph and nymph-adults and later re-transmitted to cattle during blood-meal acquisition. Consequently, the vaccine-constituting <em>T. parva</em> strains are introduced and (re) spread in non-endemic/ endemic areas. Precisely, rather than eradicating the disease, the ITM vaccination-approach promotes ECF endemicity. With advent of novel vaccination approaches toward vector and vector-borne disease control, ECF-control based on ITM of vaccination is considered outdated. The review highlights the need for embracing a holistic integrative vaccination approach entailing blocking <em>Theileria</em> pathogen-development and transmission both in the ticks and cattle, and/or the tick-population.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102386"},"PeriodicalIF":3.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000797/pdfft?md5=0a6f4b7b7b9653f8650133bd6d0de4e5&pid=1-s2.0-S1877959X24000797-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1016/j.ttbdis.2024.102387
Michela Menegon , Elisa Mancuso , Marco Di Luca , Francesca Casale , Luis Neves , Andeliza Smit , Francesco Severini , Michele Castelli , Andrea Di Giulio , Silvio G. d'Alessio , Maria Goffredo , Federica Monaco , Luciano Toma
Migratory birds play an important role in transporting ixodid ticks and tick-borne pathogens between continents. During the Boreal spring, migratory birds reach Europe, mainly from sub-Saharan Africa or from northern African countries but not much is known about the diversity and ecology of the ticks they spread. From 2017 to 2022, in the framework of two consecutive projects focused on sampling migratory birds from Africa to Europe, a total of 27 immature Amblyomma ticks were collected from migratory birds, belonging to 8 species, captured on the Island of Ventotene, an important stop-over site in the Mediterranean Sea. In the absence of adult specimens, morphological identification was limited to assigning these ticks to the Amblyomma genus. In this study, sequencing and comparative analysis of three mitochondrial molecular markers (12S rDNA, 16S rDNA, COI) were performed to achieve taxonomic identification. Sequences obtained from Ventotene specimens matched at 100% identity with Amblyomma sparsum. In conclusion, this study documented that immature stages of this species belonging to the Amblyomma marmoreum complex reached the Pontine Islands for six consecutive years. The entry of alien tick species and their potentially transmitted pathogens deserves further study, also in light of the globally ongoing climate change.
{"title":"Amblyomma sparsum Neumann 1899 on migratory birds from Africa: First records in Italy","authors":"Michela Menegon , Elisa Mancuso , Marco Di Luca , Francesca Casale , Luis Neves , Andeliza Smit , Francesco Severini , Michele Castelli , Andrea Di Giulio , Silvio G. d'Alessio , Maria Goffredo , Federica Monaco , Luciano Toma","doi":"10.1016/j.ttbdis.2024.102387","DOIUrl":"10.1016/j.ttbdis.2024.102387","url":null,"abstract":"<div><p>Migratory birds play an important role in transporting ixodid ticks and tick-borne pathogens between continents. During the Boreal spring, migratory birds reach Europe, mainly from sub-Saharan Africa or from northern African countries but not much is known about the diversity and ecology of the ticks they spread. From 2017 to 2022, in the framework of two consecutive projects focused on sampling migratory birds from Africa to Europe, a total of 27 immature <em>Amblyomma</em> ticks were collected from migratory birds, belonging to 8 species, captured on the Island of Ventotene, an important stop-over site in the Mediterranean Sea. In the absence of adult specimens, morphological identification was limited to assigning these ticks to the <em>Amblyomma</em> genus. In this study, sequencing and comparative analysis of three mitochondrial molecular markers (<em>12S</em> rDNA, <em>16S</em> rDNA, <em>COI</em>) were performed to achieve taxonomic identification. Sequences obtained from Ventotene specimens matched at 100% identity with <em>Amblyomma sparsum</em>. In conclusion, this study documented that immature stages of this species belonging to the <em>Amblyomma marmoreum</em> complex reached the Pontine Islands for six consecutive years. The entry of alien tick species and their potentially transmitted pathogens deserves further study, also in light of the globally ongoing climate change.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102387"},"PeriodicalIF":3.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000803/pdfft?md5=356394d0f60ed204fcfe9e130dbf702a&pid=1-s2.0-S1877959X24000803-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02DOI: 10.1016/j.ttbdis.2024.102385
Michael W. Dougherty , Nathan M. Russart , Robert A. Gaultney , Emily M. Gisi , Haley M. Cooper , Lindsey R. Kallis , Catherine A. Brissette , Jefferson A. Vaughan
<div><p>Lyme disease has expanded into the Great Plains of the USA. To investigate local enzootic transmission, small mammals were trapped in two forested tracts in northeastern North Dakota during 2012 and 2013. <em>Peromyscus</em> mice and southern red-backed voles, <em>Myodes gapperi,</em> comprised over 90% of all mammals captured. One site was dominated by <em>Peromyscus</em> (79% of 100 mammals captured). At the other site, <em>M. gapperi</em> (59% of 107 mammals captured) was more abundant than <em>Peromyscus</em> (36%). Immature stages of two tick species parasitized small mammals: <em>Dermacentor variabilis</em> and <em>Ixodes scapularis</em>. Larval <em>I. scapularis</em> ectoparasitism was significantly higher on <em>Peromyscus</em> (81% infested; 3.7 larvae per infested mouse) than <em>M. gapperi</em> (47% infested; 2.6 larvae per infested vole) whereas larval and nymphal <em>D. variabilis</em> ectoparasitism were highest on <em>M. gapperi</em>. Over 45% of infested rodents were concurrently infested with both tick species. Testing engorged <em>I. scapularis</em> larvae from <em>Peromyscus</em> (<em>n</em> = 66) and <em>M. gapperi</em> (<em>n</em> = 20) yielded xenopositivity prevalence for <em>Borrelia burgdorferi</em> sensu lato (s.l.) in these rodents of 6% and 5%, respectively. Progeny of field collected <em>M. gapperi</em> were used to determine host infectivity for a local isolate of <em>B. burgdorferi</em> sensu stricto (s.s.). Five <em>M. gapperi</em> were injected with spirochetes, infested with pathogen-free <em>I. scapularis</em> larvae on days 10, 20, and 40 after infection, and engorged larvae molted to nymphs. Subsamples of nymphs were tested by PCR for <em>B. burgdorferi</em> s. s<em>.</em> DNA and yielded infection rates of 56% (<em>n</em> = 100 nymphs tested), 75% (<em>n</em> = 8) and 64% (<em>n</em> = 31), respectively. The remaining infected nymphs were fed on BALB/c <em>Mus musculus</em> mice and 7 d later, mice were euthanized, and tissues were cultured for <em>B. burgdorferi</em> s.s. Nymphs successfully transmitted spirochetes to 13 of 18 (72%) mice that were exposed to 1–5 infected ticks. Theoretical reservoir potentials – i.e.<em>,</em> ability to generate <em>B. burgdorferi</em> infected nymphs – were compared between <em>Peromyscus</em> and <em>M. gapperi</em>. At one site, <em>Peromyscus</em> accounted for nearly all <em>Borrelia</em>-infected nymphs produced (reservoir potential value of 0.935). At the other site, the reservoir potentials for <em>Peromyscus</em> (0.566) and <em>M. gapperi</em> (0.434) were comparable. The difference was attributed to differences in the relative abundance of voles versus mice between sites and the higher level of ectoparasitism by larval <em>I. scapularis</em> on <em>Peromyscus</em> versus <em>M. gapperi</em> at both sites. The southern red-backed vole, <em>M. gapperi</em>, contributes to the enzootic maintenance of Lyme disease spirochetes in North Dakota and possibly othe
莱姆病已扩展到美国大平原。为了调查当地的流行病传播情况,我们于2012年和2013年在北达科他州东北部的两片森林中捕获了小型哺乳动物。捕获的所有哺乳动物中,90%以上是珀罗米鼠和南方红背田鼠(Myodes gapperi)。在一个地点,捕获的哺乳动物主要是珀罗米鼠(占捕获的 100 只哺乳动物的 79%)。在另一个地点,M. gapperi(占捕获的 107 只哺乳动物的 59%)的数量比 Peromyscus(36%)多。两种蜱的未成熟阶段寄生在小型哺乳动物身上:Dermacentor variabilis 和 Ixodes scapularis。I. scapularis幼虫在Peromyscus上的体外寄生率(81%)明显高于M. gapperi(47%;每只田鼠2.6只幼虫),而D. variabilis幼虫和若虫在M. gapperi上的体外寄生率最高。超过 45% 的受感染啮齿动物同时受到两种蜱虫的感染。对来自Peromyscus(n = 66)和M. gapperi(n = 20)的啮齿类动物的噬喙蚤幼虫进行检测,结果发现这些啮齿类动物的博氏包虫病异种阳性率(s.l. Borrelia burgdorferi sensu lato)分别为6%和5%。野外采集的 M. gapperi 的后代被用来确定当地分离的严格意义上的 B. burgdorferi(s.s.)的宿主感染性。给 5 只 M. gapperi 注射螺旋体,在感染后第 10、20 和 40 天用无病原体的 I. scapularis 幼虫进行侵染,吞食的幼虫蜕皮为若虫。通过 PCR 检测若虫的 B. burgdorferi s. s.DNA 进行检测,结果显示感染率分别为 56%(检测的若虫数量为 100 个)、75%(数量为 8 个)和 64%(数量为 31 个)。将剩余的受感染若虫喂养 BALB/c 麝香小鼠,7 天后,小鼠被安乐死,组织经培养检测 B. burgdorferi s.s.。若虫成功地将螺旋体传播给 18 只小鼠中的 13 只(72%),这些小鼠接触了 1-5 只受感染的蜱。比较了Peromyscus和M. gapperi的理论储库潜力(即产生感染B. burgdorferi的若虫的能力)。在一个地点,Peromyscus 几乎产生了所有感染 Borrelia 的若虫(蓄积潜能值为 0.935)。在另一个地点,Peromyscus(0.566)和 M. gapperi(0.434)的蓄积潜能值相当。造成这种差异的原因是不同地点田鼠与小鼠的相对丰度不同,以及两地田鼠幼虫 I. scapularis 对 Peromyscus 和 M. gapperi 的体外寄生程度较高。南方红背田鼠(M. gapperi)在北达科他州以及该啮齿类物种丰富的其他地区造成了莱姆病螺旋体的流行。
{"title":"The role of southern red-backed voles, Myodes gapperi, and Peromyscus mice in the enzootic maintenance of Lyme disease spirochetes in North Dakota, USA","authors":"Michael W. Dougherty , Nathan M. Russart , Robert A. Gaultney , Emily M. Gisi , Haley M. Cooper , Lindsey R. Kallis , Catherine A. Brissette , Jefferson A. Vaughan","doi":"10.1016/j.ttbdis.2024.102385","DOIUrl":"10.1016/j.ttbdis.2024.102385","url":null,"abstract":"<div><p>Lyme disease has expanded into the Great Plains of the USA. To investigate local enzootic transmission, small mammals were trapped in two forested tracts in northeastern North Dakota during 2012 and 2013. <em>Peromyscus</em> mice and southern red-backed voles, <em>Myodes gapperi,</em> comprised over 90% of all mammals captured. One site was dominated by <em>Peromyscus</em> (79% of 100 mammals captured). At the other site, <em>M. gapperi</em> (59% of 107 mammals captured) was more abundant than <em>Peromyscus</em> (36%). Immature stages of two tick species parasitized small mammals: <em>Dermacentor variabilis</em> and <em>Ixodes scapularis</em>. Larval <em>I. scapularis</em> ectoparasitism was significantly higher on <em>Peromyscus</em> (81% infested; 3.7 larvae per infested mouse) than <em>M. gapperi</em> (47% infested; 2.6 larvae per infested vole) whereas larval and nymphal <em>D. variabilis</em> ectoparasitism were highest on <em>M. gapperi</em>. Over 45% of infested rodents were concurrently infested with both tick species. Testing engorged <em>I. scapularis</em> larvae from <em>Peromyscus</em> (<em>n</em> = 66) and <em>M. gapperi</em> (<em>n</em> = 20) yielded xenopositivity prevalence for <em>Borrelia burgdorferi</em> sensu lato (s.l.) in these rodents of 6% and 5%, respectively. Progeny of field collected <em>M. gapperi</em> were used to determine host infectivity for a local isolate of <em>B. burgdorferi</em> sensu stricto (s.s.). Five <em>M. gapperi</em> were injected with spirochetes, infested with pathogen-free <em>I. scapularis</em> larvae on days 10, 20, and 40 after infection, and engorged larvae molted to nymphs. Subsamples of nymphs were tested by PCR for <em>B. burgdorferi</em> s. s<em>.</em> DNA and yielded infection rates of 56% (<em>n</em> = 100 nymphs tested), 75% (<em>n</em> = 8) and 64% (<em>n</em> = 31), respectively. The remaining infected nymphs were fed on BALB/c <em>Mus musculus</em> mice and 7 d later, mice were euthanized, and tissues were cultured for <em>B. burgdorferi</em> s.s. Nymphs successfully transmitted spirochetes to 13 of 18 (72%) mice that were exposed to 1–5 infected ticks. Theoretical reservoir potentials – i.e.<em>,</em> ability to generate <em>B. burgdorferi</em> infected nymphs – were compared between <em>Peromyscus</em> and <em>M. gapperi</em>. At one site, <em>Peromyscus</em> accounted for nearly all <em>Borrelia</em>-infected nymphs produced (reservoir potential value of 0.935). At the other site, the reservoir potentials for <em>Peromyscus</em> (0.566) and <em>M. gapperi</em> (0.434) were comparable. The difference was attributed to differences in the relative abundance of voles versus mice between sites and the higher level of ectoparasitism by larval <em>I. scapularis</em> on <em>Peromyscus</em> versus <em>M. gapperi</em> at both sites. The southern red-backed vole, <em>M. gapperi</em>, contributes to the enzootic maintenance of Lyme disease spirochetes in North Dakota and possibly othe","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102385"},"PeriodicalIF":3.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000785/pdfft?md5=1639aa18063521976f7606a8dacfc946&pid=1-s2.0-S1877959X24000785-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1016/j.ttbdis.2024.102383
Beate Hagenkötter , Souheil Zayet , Samantha Poloni , Vincent Gendrin , Marie Zanusso , Silviu Stancescu , Timothée Klopfenstein
We report a case of posterior reversible encephalopathy syndrome in an adult patient fulfilling criteria for proven early Lyme neuroborreliosis.
我们报告了一例成年患者的后可逆性脑病综合征病例,该患者符合经证实的早期莱姆神经源病的标准。
{"title":"Posterior reversible encephalopathy syndrome in early lyme neuroborreliosis","authors":"Beate Hagenkötter , Souheil Zayet , Samantha Poloni , Vincent Gendrin , Marie Zanusso , Silviu Stancescu , Timothée Klopfenstein","doi":"10.1016/j.ttbdis.2024.102383","DOIUrl":"10.1016/j.ttbdis.2024.102383","url":null,"abstract":"<div><p>We report a case of posterior reversible encephalopathy syndrome in an adult patient fulfilling criteria for proven early Lyme neuroborreliosis.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102383"},"PeriodicalIF":3.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000761/pdfft?md5=d2013604f73df495b68e9fd48a94d8be&pid=1-s2.0-S1877959X24000761-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24DOI: 10.1016/j.ttbdis.2024.102384
Surendra Raj Sharma , Sabir Hussain , Shailesh K. Choudhary , Scott P. Commins , Shahid Karim
Alpha-Gal Syndrome (AGS) is a delayed allergic reaction triggered by IgE antibodies targeting galactose-α-1,3-galactose (α-gal), prevalent in red meat. Its global significance has increased, with over 450,000 estimated cases in the United States alone. AGS is linked to tick bites, causing sensitization and elevated α-gal specific IgE levels. However, the precise mechanisms and tick intrinsic factors contributing to AGS development post-tick bites remain unclear. This study aims to characterize the alpha-gal conjugated lipid antigens in Amblyomma americanum (Am. americanum) salivary glands and saliva. Nanospray ionization mass spectrometry (NSI-MS) analysis revealed the identification of α-gal bound lipid antigens in Am. americanum saliva. Additionally, the activation of basophils by extracted alpha-gal bound lipids and proteins provides evidence of their antigenic capabilities.
{"title":"Identification of Alpha-Gal glycolipids in saliva of Lone-Star Tick (Amblyomma americanum)","authors":"Surendra Raj Sharma , Sabir Hussain , Shailesh K. Choudhary , Scott P. Commins , Shahid Karim","doi":"10.1016/j.ttbdis.2024.102384","DOIUrl":"10.1016/j.ttbdis.2024.102384","url":null,"abstract":"<div><p>Alpha-Gal Syndrome (AGS) is a delayed allergic reaction triggered by IgE antibodies targeting galactose-α-1,3-galactose (α-gal), prevalent in red meat. Its global significance has increased, with over 450,000 estimated cases in the United States alone. AGS is linked to tick bites, causing sensitization and elevated α-gal specific IgE levels. However, the precise mechanisms and tick intrinsic factors contributing to AGS development post-tick bites remain unclear. This study aims to characterize the alpha-gal conjugated lipid antigens in <em>Amblyomma americanum</em> (<em>Am. americanum</em>) salivary glands and saliva. Nanospray ionization mass spectrometry (NSI-MS) analysis revealed the identification of α-gal bound lipid antigens in <em>Am. americanum</em> saliva. Additionally, the activation of basophils by extracted alpha-gal bound lipids and proteins provides evidence of their antigenic capabilities.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102384"},"PeriodicalIF":3.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000773/pdfft?md5=c9b760211bf8b8ecfdca8c7b46099cef&pid=1-s2.0-S1877959X24000773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-20DOI: 10.1016/j.ttbdis.2024.102379
Jeremiah B. Reyes , Molly McVicar , Saransh Beniwal , Arvind Sharma , Richard Tillett , Juli Petereit , Andrew Nuss , Monika Gulia-Nuss
Ixodes scapularis, the black-legged tick, is a major arthropod vector that transmits the causative agents of Lyme disease and several other pathogens of human significance. The tick midgut is the main tissue involved in blood acquisition and digestion and the first organ to have contact with pathogens ingested through the blood meal. Gene expression in the midgut before, during, and after a blood meal may vary in response to the physiological changes due to blood feeding. A systems biology approach based on RNA and protein sequencing was used to gain insight into the changes in tick midgut transcripts and proteins during blood ingestion (unfed and partially fed) and digestion (1-, 2-, 7-, and 14 days post detachment from the host) by the Ixodes scapularis female ticks. A total of 2,726 differentially expressed transcripts, and 449 proteins were identified across the time points. Genes involved in detoxification of xenobiotics, proteases, protease inhibitors, metabolism, and immunity were differentially expressed in response to blood feeding. Similarly, proteins corresponding to the same groups were also differentially expressed. Nine genes from major gene categories were chosen as potential vaccine candidates, and, using RNA interference, the effect of these gene knockdowns on tick biology was investigated. Knockdown of these genes had variable negative impacts on tick physiology, such as the inability to engorge fully and to produce eggs and increased mortality. These and additional gene targets provide opportunities to explore novel tick control strategies.
{"title":"A multi-omics approach for understanding blood digestion dynamics in Ixodes scapularis and identification of anti-tick vaccine targets","authors":"Jeremiah B. Reyes , Molly McVicar , Saransh Beniwal , Arvind Sharma , Richard Tillett , Juli Petereit , Andrew Nuss , Monika Gulia-Nuss","doi":"10.1016/j.ttbdis.2024.102379","DOIUrl":"10.1016/j.ttbdis.2024.102379","url":null,"abstract":"<div><p><em>Ixodes scapularis,</em> the black-legged tick<em>,</em> is a major arthropod vector that transmits the causative agents of Lyme disease and several other pathogens of human significance. The tick midgut is the main tissue involved in blood acquisition and digestion and the first organ to have contact with pathogens ingested through the blood meal. Gene expression in the midgut before, during, and after a blood meal may vary in response to the physiological changes due to blood feeding. A systems biology approach based on RNA and protein sequencing was used to gain insight into the changes in tick midgut transcripts and proteins during blood ingestion (unfed and partially fed) and digestion (1-, 2-, 7-, and 14 days post detachment from the host) by the <em>Ixodes scapularis</em> female ticks. A total of 2,726 differentially expressed transcripts, and 449 proteins were identified across the time points. Genes involved in detoxification of xenobiotics, proteases, protease inhibitors, metabolism, and immunity were differentially expressed in response to blood feeding. Similarly, proteins corresponding to the same groups were also differentially expressed. Nine genes from major gene categories were chosen as potential vaccine candidates, and, using RNA interference, the effect of these gene knockdowns on tick biology was investigated. Knockdown of these genes had variable negative impacts on tick physiology, such as the inability to engorge fully and to produce eggs and increased mortality. These and additional gene targets provide opportunities to explore novel tick control strategies.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102379"},"PeriodicalIF":3.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000724/pdfft?md5=b3d85f71955aebabbb5fad285334949f&pid=1-s2.0-S1877959X24000724-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-20DOI: 10.1016/j.ttbdis.2024.102382
Lucía de Dios-Blázquez , Ana Laura Cano-Argüelles , Ricardo Pérez-Sánchez , María González-Sánchez , Ana Oleaga
Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, tick proteins involved in cholesterol absorption and transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets for anti-tick vaccine development. The aim of this study was to assess the structure, function, and protective efficacy of the NPC1 orthologues identified previously in the midgut transcriptomes of argasid ticks Ornithodoros erraticus and Ornithodoros moubata. For this purpose, their corresponding cDNA coding sequences were cloned and sequenced, their secondary and 3D structures were predicted, and their function was evaluated through RNAi-mediated gene knockdown and in vitro feeding on blood supplemented with ezetimibe, which inhibits cholesterol binding by NPC1 proteins. Subsequently, the protective efficacy of a recombinant form of NPC1 from O. moubata (rOmNPC1) was tested in a rabbit vaccine trial. While inhibiting cholesterol absorption with ezetimibe resulted in up to 77 % mortality in adult O. moubata, NPC1 gene knockdown and vaccination with rOmNPC1 decreased female reproductive performance in terms of the number and fertility of laid eggs. This study presents the initial molecular and functional insights into NPC1 proteins in soft ticks and supports the hypothesis that disrupting cholesterol metabolism diminishes tick viability and reproduction, rendering Niemann-Pick type C1 domain-containing proteins promising targets for drugs or vaccines.
{"title":"First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins","authors":"Lucía de Dios-Blázquez , Ana Laura Cano-Argüelles , Ricardo Pérez-Sánchez , María González-Sánchez , Ana Oleaga","doi":"10.1016/j.ttbdis.2024.102382","DOIUrl":"10.1016/j.ttbdis.2024.102382","url":null,"abstract":"<div><p>Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, tick proteins involved in cholesterol absorption and transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets for anti-tick vaccine development. The aim of this study was to assess the structure, function, and protective efficacy of the NPC1 orthologues identified previously in the midgut transcriptomes of argasid ticks <em>Ornithodoros erraticus</em> and <em>Ornithodoros moubata</em>. For this purpose, their corresponding cDNA coding sequences were cloned and sequenced, their secondary and 3D structures were predicted, and their function was evaluated through RNAi-mediated gene knockdown and <em>in vitro</em> feeding on blood supplemented with ezetimibe, which inhibits cholesterol binding by NPC1 proteins. Subsequently, the protective efficacy of a recombinant form of NPC1 from <em>O. moubata</em> (rOmNPC1) was tested in a rabbit vaccine trial. While inhibiting cholesterol absorption with ezetimibe resulted in up to 77 % mortality in adult <em>O. moubata</em>, NPC1 gene knockdown and vaccination with rOmNPC1 decreased female reproductive performance in terms of the number and fertility of laid eggs. This study presents the initial molecular and functional insights into NPC1 proteins in soft ticks and supports the hypothesis that disrupting cholesterol metabolism diminishes tick viability and reproduction, rendering Niemann-Pick type C1 domain-containing proteins promising targets for drugs or vaccines.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102382"},"PeriodicalIF":3.1,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X2400075X/pdfft?md5=a4433a0e0c8368d094ad095e5be25fbc&pid=1-s2.0-S1877959X2400075X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1016/j.ttbdis.2024.102375
Yunxiao Wang , Ruiling Zhang , Xiurong Wang , Xudong Zhang , Zhong Zhang , Michael J. Carr , Guangfu Yu , Hong Zhou , Weifeng Shi
Nairobi Sheep Disease (NSD) is a typical tick-borne syndrome characterized by severe hemorrhagic gastroenteritis, spontaneous abortion, and a high case fatality rate in small ruminants. The pathogenic agent, Nairobi sheep disease virus (NSDV), has also been associated with human infections, indicating its possible zoonotic potential. Prior to this study, NSDV has been detected from ticks collected in Jilin, Hubei, and Liaoning provinces in China. In the present study, a total of 343 ticks (Haemaphysalis longicornis) were collected in Shandong province, China in 2020, and pooled into 16 libraries. Analysis of the meta-transcriptomic sequencing data identified NSDV strains SDWL07, SDWL08, and SDWL16 from three pools. The SDWL07 and SDWL16 strains were detected from unfed ticks, while SDWL08 was detected from cattle-feeding ticks. Phylogenetic analyses showed higher sequence identities between the three strains and other Chinese NSDV strains than those from India and Kenya. Phylogenetic analyses also revealed that they clustered together and fell within the China lineage, suggesting no potential genetic reassortment among them. In summary, this is the first report of the identification of NSDV in Shandong province, highlighting the continually expanding endemic regions of this pathogen. Surveillance of NSDV should be intensified in China, especially in areas where H. longicornis is endemic.
{"title":"Identification and phylogenetic analysis of Nairobi sheep disease virus from Haemaphysalis longicornis ticks in Shandong Province, China","authors":"Yunxiao Wang , Ruiling Zhang , Xiurong Wang , Xudong Zhang , Zhong Zhang , Michael J. Carr , Guangfu Yu , Hong Zhou , Weifeng Shi","doi":"10.1016/j.ttbdis.2024.102375","DOIUrl":"10.1016/j.ttbdis.2024.102375","url":null,"abstract":"<div><p>Nairobi Sheep Disease (NSD) is a typical tick-borne syndrome characterized by severe hemorrhagic gastroenteritis, spontaneous abortion, and a high case fatality rate in small ruminants. The pathogenic agent, Nairobi sheep disease virus (NSDV), has also been associated with human infections, indicating its possible zoonotic potential. Prior to this study, NSDV has been detected from ticks collected in Jilin, Hubei, and Liaoning provinces in China. In the present study, a total of 343 ticks (<em>Haemaphysalis longicornis</em>) were collected in Shandong province, China in 2020, and pooled into 16 libraries. Analysis of the meta-transcriptomic sequencing data identified NSDV strains SDWL07, SDWL08, and SDWL16 from three pools. The SDWL07 and SDWL16 strains were detected from unfed ticks, while SDWL08 was detected from cattle-feeding ticks. Phylogenetic analyses showed higher sequence identities between the three strains and other Chinese NSDV strains than those from India and Kenya. Phylogenetic analyses also revealed that they clustered together and fell within the China lineage, suggesting no potential genetic reassortment among them. In summary, this is the first report of the identification of NSDV in Shandong province, highlighting the continually expanding endemic regions of this pathogen. Surveillance of NSDV should be intensified in China, especially in areas where <em>H. longicornis</em> is endemic.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102375"},"PeriodicalIF":3.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000682/pdfft?md5=f5482294951c0b792f501a69c0ecfec3&pid=1-s2.0-S1877959X24000682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141623936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1016/j.ttbdis.2024.102377
Hermes Ribeiro Luz , Carlos Eduardo Costa de Campos , Livio Martins Costa-Junior , Ercileide Silva Santos , Adriani Hass , Dauana Mesquita Sousa , Ruth Myrian de Moares e Silva , Josiane Moreira Rocha , George Rego Albuquerque , Antonio Jorge Argolo , Rogério Zacariotti , Catia Dejuste de Paula , Luiz Cezar Machado Pereira , Patricia Avello Nicola , João Luiz Horacio Faccini , Mauricio Claudio Horta , Rafael Michael Silva Nogueira , Leonardo Teixeira DallAgnol , Marcelo Bahia Labruna , Thiago Fernandes Martins
Ticks parasitize a wide variety of wild animals, including amphibians and reptiles. In addition to the possibility of microorganism transmission to these hosts, ticks can also cause severe bleeding, and high parasitism can lead to death. Therefore, knowing the diversity of ticks parasitizing amphibians and reptiles is important for conservation and preservation measures for these vertebrates. In the present study, we report parasitism by ticks in amphibians and reptiles from different Brazilian biomes (Amazon, Caatinga, Cerrado and Atlantic Forest). Ticks were collected from amphibians and reptiles deposited from the Herpetological Collection of the Federal University of Maranhão (UFMA), São Luís (Maranhão State), the State University Santa Cruz (UESC), Ilhéus (Bahia State), and the Federal University of São Francisco Valley (Univasf), Petrolina (Pernambuco State). Additionally, ticks were collected from amphibians and reptiles captured and road-killed in the Amazon biome, at Maranhão and Amapá States. Specimens of ticks were photographed under a Zeiss stereomicroscope (5.1 zoom). Map with the locations were made using the Qgis program. Overall, 1973 specimens of amphibians and reptiles were examined. A total of 927 ticks were collected: 98 larvae, 421 nymphs and 408 adults. Six species of ticks were identified: Amblyomma rotundatum and Amblyomma dissimile the most frequent, and Amblyomma cajennense sensu stricto, Amblyomma sculptum, Amblyomma nodosum and Amblyomma humerale, occasionally. Surprisingly, a total of twelve males of A. rotundatum were collected. Here we report new records of association between cold-blooded animals and ticks and reinforce the absence of A. dissimile in the Caatinga, Cerrado and Atlantic Forest biomes. Additionally, we report new records of A. rotundatum males on reptiles in the Amazon biome. This last record allows us to speculate about a possible association of A. rotundatum males with reptiles and the Amazon biome.
{"title":"Ticks parasitizing cold-blooded animals from three different Brazilian biomes; with note for males of Amblyomma rotundatum","authors":"Hermes Ribeiro Luz , Carlos Eduardo Costa de Campos , Livio Martins Costa-Junior , Ercileide Silva Santos , Adriani Hass , Dauana Mesquita Sousa , Ruth Myrian de Moares e Silva , Josiane Moreira Rocha , George Rego Albuquerque , Antonio Jorge Argolo , Rogério Zacariotti , Catia Dejuste de Paula , Luiz Cezar Machado Pereira , Patricia Avello Nicola , João Luiz Horacio Faccini , Mauricio Claudio Horta , Rafael Michael Silva Nogueira , Leonardo Teixeira DallAgnol , Marcelo Bahia Labruna , Thiago Fernandes Martins","doi":"10.1016/j.ttbdis.2024.102377","DOIUrl":"10.1016/j.ttbdis.2024.102377","url":null,"abstract":"<div><p>Ticks parasitize a wide variety of wild animals, including amphibians and reptiles. In addition to the possibility of microorganism transmission to these hosts, ticks can also cause severe bleeding, and high parasitism can lead to death. Therefore, knowing the diversity of ticks parasitizing amphibians and reptiles is important for conservation and preservation measures for these vertebrates. In the present study, we report parasitism by ticks in amphibians and reptiles from different Brazilian biomes (Amazon, Caatinga, Cerrado and Atlantic Forest). Ticks were collected from amphibians and reptiles deposited from the Herpetological Collection of the Federal University of Maranhão (UFMA), São Luís (Maranhão State), the State University Santa Cruz (UESC), Ilhéus (Bahia State), and the Federal University of São Francisco Valley (Univasf), Petrolina (Pernambuco State). Additionally, ticks were collected from amphibians and reptiles captured and road-killed in the Amazon biome, at Maranhão and Amapá States. Specimens of ticks were photographed under a Zeiss stereomicroscope (5.1 zoom). Map with the locations were made using the Qgis program. Overall, 1973 specimens of amphibians and reptiles were examined. A total of 927 ticks were collected: 98 larvae, 421 nymphs and 408 adults. Six species of ticks were identified: <em>Amblyomma rotundatum</em> and <em>Amblyomma dissimile</em> the most frequent, and <em>Amblyomma cajennense</em> sensu stricto, <em>Amblyomma sculptum, Amblyomma nodosum</em> and <em>Amblyomma humerale</em>, occasionally. Surprisingly, a total of twelve males of <em>A. rotundatum</em> were collected. Here we report new records of association between cold-blooded animals and ticks and reinforce the absence of <em>A. dissimile</em> in the Caatinga, Cerrado and Atlantic Forest biomes. Additionally, we report new records of <em>A. rotundatum</em> males on reptiles in the Amazon biome. This last record allows us to speculate about a possible association of <em>A. rotundatum</em> males with reptiles and the Amazon biome.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102377"},"PeriodicalIF":3.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000700/pdfft?md5=ec6dc23da8ff74c866ac9ca63f64487a&pid=1-s2.0-S1877959X24000700-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141623958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-13DOI: 10.1016/j.ttbdis.2024.102380
Mai Kishimoto , Yukari Itakura , Koshiro Tabata , Rika Komagome , Hiroki Yamaguchi , Kohei Ogasawara , Ryo Nakao , Yongjin Qiu , Kozue Sato , Hiroki Kawabata , Masahiro Kajihara , Naota Monma , Junji Seto , Asako Shigeno , Masayuki Horie , Michihito Sasaki , William W. Hall , Hirofumi Sawa , Yasuko Orba , Keita Matsuno
Beiji nairovirus (BJNV), in the family Nairoviridae, the order Bunyavirales, was recently reported as a causative agent of an emerging tick-borne zoonotic infection in China. This study investigated the prevalence of BJNV in ticks in Japan. Screening of over 2,000 ticks from multiple regions revealed a widespread distribution of BJNV and BJNV-related viruses in Japan, particularly in the northern island, and in other high altitude areas with exclusive occurrence of Ixodes ticks. Phylogenetic analysis identified three distinct groups of nairoviruses in ticks in Japan: BJNV, Yichun nairovirus (YCNV) and a newly identified Mikuni nairovirus (MKNV). BJNV and YCNV variants identified in ticks in Japan exhibited high nucleotide sequence identities to those in China and Russia with evidence of non-monophyletic evolution among BJNVs, suggesting multiple cross-border transmission events of BJNV between the Eurasian continent and Japan. Whole genome sequencing of BJNV and MKNV revealed a unique GA-rich region in the S segment, the significance of which remains to be determined. In conclusion, the present study has shown a wide distribution and diversity of BJNV-related nairoviruses in Ixodes ticks in Japan and has identified unique genomic structures. The findings demonstrate the significance of BJNV as well as related viruses in Japan and highlight the necessity of monitoring emerging nairovirus infections and their potential risks to public health.
{"title":"A wide distribution of Beiji nairoviruses and related viruses in Ixodes ticks in Japan","authors":"Mai Kishimoto , Yukari Itakura , Koshiro Tabata , Rika Komagome , Hiroki Yamaguchi , Kohei Ogasawara , Ryo Nakao , Yongjin Qiu , Kozue Sato , Hiroki Kawabata , Masahiro Kajihara , Naota Monma , Junji Seto , Asako Shigeno , Masayuki Horie , Michihito Sasaki , William W. Hall , Hirofumi Sawa , Yasuko Orba , Keita Matsuno","doi":"10.1016/j.ttbdis.2024.102380","DOIUrl":"10.1016/j.ttbdis.2024.102380","url":null,"abstract":"<div><p>Beiji nairovirus (BJNV), in the family <em>Nairoviridae</em>, the order <em>Bunyavirales</em>, was recently reported as a causative agent of an emerging tick-borne zoonotic infection in China. This study investigated the prevalence of BJNV in ticks in Japan. Screening of over 2,000 ticks from multiple regions revealed a widespread distribution of BJNV and BJNV-related viruses in Japan, particularly in the northern island, and in other high altitude areas with exclusive occurrence of <em>Ixodes</em> ticks. Phylogenetic analysis identified three distinct groups of nairoviruses in ticks in Japan: BJNV, Yichun nairovirus (YCNV) and a newly identified Mikuni nairovirus (MKNV). BJNV and YCNV variants identified in ticks in Japan exhibited high nucleotide sequence identities to those in China and Russia with evidence of non-monophyletic evolution among BJNVs, suggesting multiple cross-border transmission events of BJNV between the Eurasian continent and Japan. Whole genome sequencing of BJNV and MKNV revealed a unique GA-rich region in the S segment, the significance of which remains to be determined. In conclusion, the present study has shown a wide distribution and diversity of BJNV-related nairoviruses in <em>Ixodes</em> ticks in Japan and has identified unique genomic structures. The findings demonstrate the significance of BJNV as well as related viruses in Japan and highlight the necessity of monitoring emerging nairovirus infections and their potential risks to public health.</p></div>","PeriodicalId":49320,"journal":{"name":"Ticks and Tick-borne Diseases","volume":"15 6","pages":"Article 102380"},"PeriodicalIF":3.1,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1877959X24000736/pdfft?md5=4e7ba51c65498aa470bcda45c4c01065&pid=1-s2.0-S1877959X24000736-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}