A RHESUS MACAQUE MODEL OF STREPTOCOCCUS PNEUMONIAE CARRIAGE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 表示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。S.肺炎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生率。因此，我们决定建立一个恒河猴S。肺炎携带，以补充和改进现有的啮齿动物模型，其中动物的NP解剖结构和上皮衬里更类似于人。我们首先调查了来自该中心繁殖群的幼年恒河猴的鼻咽，以寻找天然携带者的动物。共158只恒河猴，中位年龄为1.23岁（范围0.59  1.99）进行了调查。没有S。从任何动物中分离肺炎菌菌落。因此恒河猴不可能是S.肺炎。第二，我们尝试通过NP滴注人S. pneumoniae菌株（19 F）。这在抗生素预处理和未处理的动物中进行。我们还研究了继发于定植的肺炎和播散性感染，以及脾切除术是否会促进这些感染。NP定植率在滴注后2周（PI）保持在100%，7周保持在60%以上。然后在30%左右振荡，直到研究结束的第14周;它似乎不受抗生素预处理的影响。在PI第5周和第6周之间，对4只动物进行脾切除术。在任何时间，脾切除或正常脾切除的任何动物均未出现侵袭性感染或疾病。血液和支气管肺泡灌洗液培养始终呈阴性，X线、CBC和血清化学分析始终正常。我们的结论是，恒河猴是一个合适的模型来研究肺炎球菌定植。然而，在该模型中，脾切除术可能不会促进向侵袭性疾病的转变。

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.