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: 10430326
• 负责人: Matthew John Valentine
• 金额: $ 5.13万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10430326
• 关键词: 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; Diagnosis; Diagnostic; Didelphidae; Disease; Doxycycline; Environment; Etiology; 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; 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.

由立克菲利斯（Rickettsia felis）引起的跳蚤传播斑点发烧（FBSF），克细胞内 细菌是最近描述的（1994年）的新兴疾病 描述了全球。猫跳蚤是确认的生物学载体和储层，尽管滴答了 蚊子可以藏有R. Felis。由于FBSF的临床体征是非特异性的，并且感染 可能是无症状的，疾病可能会大大不足。尽管如此， 由血液PCR确定的感染在国家的热火患者中尤为常见 在非洲和亚洲。迄今为止，R。Felis尚未与FBSF患者的血液中分离出来。 作为一种新描述的疾病，有许多与FBSF有关的问题，包括 其他载体的可能性，发病机理和对感染的免疫反应，甚至 R. felis是否可能不是致病性的，并且仅作为人类寄生虫的象征或 原虫。随着进一步的患者数据逐渐积累，这些问题将得到解决，并且 可以进行临床试验。但是，适当的动物模型将极大地促进 并加速了有关FBSF的未解决问题的投资。很遗憾， 关于动物感染的唯一信息，来自猫，狗，豚鼠，小鼠，骨和 大鼠，表明没有合适的模型。最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身体上与人类之间的关系更紧密。 日期关于NHP中的R. felis的唯一数据是可以在粪便中找到生物体。 我们研究的目的是确定非洲绿猴是否（氯康布斯Aethiops） Sabaeus（AGM）易受LSU的实验感染（静脉接种） Felis菌株。感染后，将监测AGM的临床体征，Rickettsemia通过PCR监测 和培养，抗体反应以及人体器官损伤和功能障碍。只有最小值 满足研究目的所需的动物数量将被使用，这些动物将被安置 在露天的专用设施中，避免了昆虫，但紧密地反映了他们的自然环境 在加勒比岛圣基茨岛的研究地点。会产生严重迹象的AGM 强力霉素，建议在人们治疗的抗生素，这将使详细 检查药物的效率。如果AGM的预后迹象很严重，那么它们 将被人性化的安乐死和死灵，以确定感染的发病机理。 如果发现AGM易感性，研究的数据将帮助研究人员决定 如果AGM是可用于未来发病机理的felis感染的合适模型， 传播，诊断和/或治疗研究。