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.

蚤传斑点热（FBSF）由猫立克次体（一种革兰氏细胞内 细菌，是最近描述的（1994）新兴疾病的人，现在已经 描述世界各地。猫蚤是已确认的生物媒介和宿主， 蚊子也可以携带R.猫由于FBSF的临床症状是非特异性的， 可能是无症状的，可能有相当大的漏报的疾病。然而，尽管如此， 通过血液PCR确定的感染在一些国家的发热患者中特别常见， 在非洲和亚洲。对R.尚未从FBSF患者的血液中分离出猫。 作为一种新描述的疾病，存在许多与FBSF相关的问题，包括 其他载体的可能性，致病机理和对感染的免疫反应，甚至 R.猫可能不是致病性的，仅作为人类寄生虫的共生体被检测到， 原生动物。这些问题将随着更多患者数据的慢慢积累而得到解决， 可以进行临床试验。然而，适当的动物模型将极大地促进 并加快对FBSF未解之谜的调查不幸的是， 关于动物感染的唯一信息，包括猫、狗、豚鼠、小鼠、负鼠和 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的 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。到 这是R的唯一数据。NHP中的猫是有机体可以在他们的粪便中找到。 本研究的目的是确定非洲绿色猴（Chlorocebus aethiops sabaeus）（AGM）对LSU的实验感染（静脉接种）敏感 菌株R.猫感染后，将通过PCR监测AGM的临床体征、立克次体 以及培养、抗体反应、身体器官损伤和功能障碍。只有最低限度 将使用满足研究目的所需的动物数量，并将其圈养 在露天的专用设施中，这些设施既能防虫，又能密切反映其自然环境 在加勒比海圣基茨岛的研究地点。出现严重迹象的年度股东大会将被给予 强力霉素，推荐用于治疗的抗生素，这将使详细的 检查药物的功效。如果AGM出现非常严重的症状，预后不良， 将被人道处死并进行尸检，以确定感染的发病机制。 如果发现AGM易受影响，研究数据将有助于研究人员决定 如果AGM是R.可以用于未来发病机制的猫感染， 传播、诊断和/或治疗研究。