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

细胞内革兰氏立克次体引起的跳蚤传播斑点热(FBSF) 细菌，是最近(1994)描述的一种新出现的人类疾病，现在已经 在世界范围内被描述。猫蚤是已证实的生物媒介和宿主，尽管扁虱 而且蚊子也可以窝藏猫狂犬病。由于FBSF的临床症状是非特异性和感染性的 可能是无症状的，可能会有相当大的漏报疾病。不过， 通过血液聚合酶链式反应确定的感染，在一些国家的发烧患者中尤其常见。 在非洲和亚洲。到目前为止，还没有从FBSF患者的血液中分离到费氏杆菌。 作为一种新描述的疾病，与FBSF有关的问题很多，包括 其他载体的可能性、发病机制和对感染的免疫反应，甚至 费氏杆菌是否可能不是致病的，只作为人类寄生虫的共生体被检测出来，还是 原生动物。这些问题将随着进一步的患者数据慢慢积累和 可能会进行临床试验。然而，一个合适的动物模型将极大地促进 并加快调查围绕FBSF的悬而未决的问题。不幸的是， 关于动物感染的唯一信息，来自猫、狗、豚鼠、老鼠、负鼠和 大鼠，表明没有一个是合适的模型。最有可能的动物模型应该是非人类的 灵长类(NHP)，因为它们在解剖学和生理学上与人类更接近。至 目前，有关非霍乱弧菌的唯一数据是，在它们的粪便中可以找到这种微生物。 我们研究的目的是确定非洲绿猴(ChlorOcean Bus Atheiops) Sabaeus)(AGM)对LSU的实验性感染(静脉接种)很敏感 费氏乳杆菌菌株。感染后，将通过聚合酶链式反应监测巨噬细胞病的临床症状和立克次体症状。 培养，抗体反应，以及身体器官损伤和功能障碍。只有最低限度的 达到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，专用的设施是防虫的，但与他们的自然环境非常接近 在加勒比海圣基茨岛的研究地点。出现严重症状的股东周年大会将被给予 多西环素，推荐用于人类治疗的抗生素，它将使详细的 检查药物的疗效。如果动员会出现非常严重的症状，预后很差，他们会 将被人道地实施安乐死和身体解剖以确定感染的发病机制。 如果发现股东周年大会易受影响，研究数据将帮助研究人员决定 如果AGMS是可以用于未来发病机制的合适的费氏杆菌感染模型， 传播、诊断和/或治疗研究。

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.