Susceptibility of African Green Monkeys (Chlorocebus aethiops sabaeus) to Rickettsia felis, the agent of flea-borne spotted fever

非洲绿猴（Chlorocebus aethiops sabaeus）对猫立克次体（跳蚤传播的斑疹热病原）的敏感性

• 批准号: 10606549
• 负责人: Matthew John Valentine
• 金额: $ 5.37万
• 依托单位: ROSS UNIVERSITY SCH/VETERINARY MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-08 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10606549
• 关键词: Acceleration; Africa; African Green Monkey; Air; Anatomy; Animal Model; Animals; Antibiotics; Antibody Response; Asia; Attention; Autopsy; Bacteria; Behavioral Sciences; Biochemical; Biological; Blood; Body Weight decreased; Canis familiaris; Caribbean region; Caring; Cavia; Child; Clinical; Clinical Trials; Collaborations; Coughing; Country; Culicidae; Data; Dedications; Diagnosis; Diagnostic; Didelphidae; Disease; Doxycycline; Environment; Etiology; Euthanasia; Exanthema; Faculty; Feces; Felis catus; Fever; Fleas; Foundations; Functional disorder; Future; Hematology; Human; Immune response; Immunologics; Infection; Insecta; Intravenous; Investigation; Island; Laboratories; Laboratory Animals; Mental Depression; Modeling; Modernization; Monitor; Mus; Myalgia; Organ; Organism; Parasites; Pathogenesis; Pathogenicity; Patients; Persons; Physiological; Population; Predisposition; Prognosis; Publications; Rattus; Reaction; Recommendation; Recording of previous events; Reporting; Research; Research Personnel; Rickettsia felis; Serology; Site; Testing; Ticks; Time; Universities; Vector-transmitted infectious disease; Veterinary Medicine; Veterinary Schools; West Indies; appetite loss; college; drug efficacy; flea-borne; gastrointestinal sign; high risk; human model; nonhuman primate; spotted fever; symbiont; transmission process; vector

Flea-borne spotted fever (FBSF) caused by Rickettsia felis, a Gram -ve intracellular bacterium, is a recently described (1994) emerging disease of people that has now been described worldwide. The cat flea is the confirmed biological vector and reservoir although ticks and mosquitoes can harbor R. felis. Since clinical signs of FBSF are non-specific and infections can be asymptomatic, there might be considerable underreporting of the disease. Nevertheless, infections, as determined by PCR of blood, are particularly common in febrile patients in countries in Africa and Asia. To date R. felis has not been isolated from the blood of a FBSF patient. As a newly described disease there are many questions relating to FBSF, including the possibility of other vectors, the pathogenesis and immune responses to infection, and even as to whether R. felis might not be pathogenic and detected only as a symbiont of a human parasite or protozoan. These questions will be resolved as further patient data slowly accumulates and clinical trials may be carried out. However, an appropriate animal model would greatly facilitate and accelerate the investigation of the unanswered questions surrounding FBSF. Unfortunately, the only information on infections in animals, from cats, dogs, guinea pigs, mice, opossums, and rats, indicate none are suitable models. The most likely animal model should be a non-human primate (NHP) as they are more closely related, anatomically and physiologically, to humans. To date the only data on R. felis in NHPs is that the organism can be found in their feces. The aim of our study is to determine if African green monkeys (Chlorocebus aethiops sabaeus) (AGMs) are susceptible to experimental infection (intravenous inoculation) with the LSU strain of R. felis. After infection, AGMs will be monitored for clinical signs, rickettsemia by PCR and culture, antibody responses, and body organ damage and dysfunction. Only the minimum number of animals required to meet the aim of the study will be used, and these will be housed in open-air, dedicated facilities that are insect-proof but closely mirror their natural environment at the study site on the Caribbean island of St Kitts. AGMs that develop severe signs will be given doxycycline, the antibiotic recommended for treatment in people, which will enable a detailed examination of the drug’s efficacy. If AGMs develop very severe signs with a poor prognosis, they will be humanely euthanized and necropsied to determine the pathogenesis of infections. If the AGMs are found susceptible, the data from the study will help researchers to decide if AGMs are suitable models of R. felis infections that can be used in future pathogenesis, transmission, diagnosis, and/or treatment studies.

由革兰氏阴性细胞内立克次体引起的跳蚤传播斑疹热 (FBSF) 细菌，是最近（1994）描述的一种新出现的人类疾病，现已被 尽管猫跳蚤是已被证实的生物媒介和宿主蜱。 由于 FBSF 的临床症状是非特异性的并且感染，蚊子可能含有猫 R. felis。 可能是无症状的，但可能存在大量的疾病漏报情况。 通过血液 PCR 确定的感染在一些国家的发热患者中尤其常见 迄今为止，非洲和亚洲尚未从 FBSF 患者的血液中分离出猫 R. felis。 作为一种新描述的疾病，有许多与 FBSF 相关的问题，包括 其他媒介的可能性、发病机制和对感染的免疫反应，甚至 猫红线虫是否可能不具有致病性并且仅作为人类寄生虫的共生体被检测到，或者 随着进一步的患者数据的慢慢积累和研究，这些问题将会得到解决。 然而，适当的动物模型将极大地促进临床试验的进行。 并加速对有关 FBSF 的未解答问题的调查 不幸的是， 关于猫、狗、豚鼠、小鼠、负鼠等动物感染的唯一信息 大鼠，表明没有合适的模型，最有可能的动物模型应该是非人类。 灵长类动物（NHP），因为它们在解剖学和生理学上与人类更密切相关。 迄今为止，关于 NHP 中猫科动物的唯一数据是，可以在其粪便中找到该生物体。 我们研究的目的是确定非洲绿猴（Chlorocebus aethiops）是否 sabaeus）（AGM）对 LSU 的实验性感染（静脉接种）敏感 感染后，将通过 PCR 监测 AGM 的临床症状、立克次血症。 以及培养、抗体反应以及身体器官损伤和功能障碍。 将使用达到研究目标所需的动物数量，并将这些动物安置在 在露天专用设施中，防虫但又密切反映其自然环境 在加勒比圣基茨岛的研究地点，出现严重迹象的年度股东大会将发出警告。 多西环素，推荐用于人类治疗的抗生素，这将使详细的 检查药物的疗效 如果 AGM 出现非常严重的症状且预后不良，则应进行检查。 将被人道地安乐死并进行尸检以确定感染的发病机制。 如果发现年度股东大会容易受到影响，研究数据将帮助研究人员做出决定 如果 AGM 是可用于未来发病机制的猫 R. felis 感染的合适模型， 传播、诊断和/或治疗研究。