A RHESUS MACAQUE MODEL OF STREPTOCOCCUS PNEUMONIAE CARRIAGE

肺炎链球菌携带的恒河猴模型

• 批准号: 8358165
• 负责人: MARIO TOMAS PHILIPP
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358165
• 关键词: Affect; Age; Anatomy; Animals; Antibiotics; Blood; Breeding; Cessation of life; Chemistry; Complement; Disease; Epithelial; Fostering; Funding; Grant; Human; Incidence; Infant; Infection; Macaca mulatta; Modeling; Nasopharynx; National Center for Research Resources; Pneumococcal Colonization; Pneumococcal Infections; Pneumonia; Primates; Principal Investigator; Procedures; Research; Research Infrastructure; Resources; Rodent Model; Roentgen Rays; Secondary to; Serum; Source; Splenectomy; Streptococcus pneumoniae; Surveys; Time; United States National Institutes of Health; cost; improved; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pneumococcal infection causes an estimated 40,000 deaths annually in the US. Colonization of the nasopharynx by S. pneumoniae always precedes pneumococcal disease. Therefore, elucidation of procedures to prevent or eradicate nasopharyngeal (NP) carriage would help diminish the incidence of both pneumonia and invasive disease. We thus endeavored to develop a rhesus monkey model of S. pneumoniae carriage, to complement and improve upon the existing rodent models, with an animal whose NP anatomy and epithelial lining is more akin to the human. We first surveyed the nasopharynx of infant rhesus macaques from the Center's breeding colony, in search of animals that were natural carriers. A total of 158 rhesus of a median age of 1.23 years (range 0.59  1.99) were surveyed. No S. pneumoniae colonies were isolated from any of the animals. Thus rhesus are not likely natural carriers of S. pneumoniae. Second, we attempted to induce carriage experimentally in infants (n = 8), by NP instillation of a human S. pneumoniae strain (19F). This was done both in antibiotic pre-treated and untreated animals. We also searched for pneumonia and disseminated infection secondary to colonization, and whether these forms of infection could be facilitated by splenectomy. The rate of NP colonization remained at 100% for 2 weeks post-instillation (PI), and above 60% for 7 weeks. It then oscillated around 30% until week 14, when the study ended; it did not appear to be affected by antibiotic pre-treatment. Four of the animals were splenectomized between weeks 5 and 6 PI. There was no invasive infection or disease in any of the animals, splenectomized or eusplenic, at any time. Blood and BAL cultures were negative throughout, and X-rays, CBC, and serum chemistry analyses were normal at all times. We concluded that the rhesus monkey is a suitable model to study pneumococcal colonization. However, the transition to invasive disease may not be fostered by splenectomy in this model.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 在美国，肺炎球菌感染每年估计导致 40,000 人死亡。肺炎链球菌在鼻咽部定植总是先于肺炎球菌疾病。因此，阐明预防或根除鼻咽（NP）携带的程序将有助于减少肺炎和侵袭性疾病的发病率。因此，我们致力于开发肺炎链球菌携带的恒河猴模型，以补充和改进现有的啮齿动物模型，该动物的鼻孔解剖结构和上皮内衬更类似于人类。我们首先调查了该中心繁殖群的幼年恒河猴的鼻咽部，寻找天然携带者的动物。总共调查了 158 只恒河猴，中位年龄为 1.23 岁（范围 0.59 - 1.99）。没有从任何动物中分离出肺炎链球菌菌落。因此，恒河猴不太可能是肺炎链球菌的天然携带者。其次，我们尝试通过 NP 滴注人肺炎链球菌菌株 (19F) 来实验性地诱导婴儿 (n = 8) 携带。这是在经过抗生素预处理和未经抗生素处理的动物中进行的。我们还寻找了继发于定植的肺炎和播散性感染，以及脾切除是否可以促进这些形式的感染。滴注后 (PI) 2 周内，NP 定植率保持在 100%，并在 7 周内保持在 60% 以上。然后它在 30% 左右波动，直到第 14 周研究结束；它似乎不受抗生素预处理的影响。其中四只动物在感染后第 5 周至第 6 周期间被切除脾脏。在任何时间，任何被切除脾脏或无脾的动物都没有出现侵袭性感染或疾病。血液和 BAL 培养自始至终呈阴性，X 射线、CBC 和血清化学分析始终正常。我们的结论是，恒河猴是研究肺炎球菌定植的合适模型。然而，在此模型中，脾切除可能不会促进向侵袭性疾病的转变。