Pathogenesis & molecular epidemiology of Pneumococcal infection in Sickle Cell

患有镰状细胞病的患者患严重肺炎球菌感染的风险增加400倍。 其他被包裹的病原体或其他贫血不具有这种风险，这表明有一种 肺炎球菌病的严重程度与SS表型之间的潜在因果关系。这 应用寻求调查镰状细胞病肺炎球菌感染的两个方面。超过了 上一个赠款周期，肺炎球菌发病机制计划和SS之间的合作 移植小鼠模型显示PAF受体是侵袭性增加的关键决定因素 疾病。特定的受体拮抗剂可以改善疾病的结局。这提供了一个可供检验的模型 严重疾病的细菌和宿主决定因素将在下一个赠款期间进行研究。 建立在该中心对具有抗生素耐药性的SS患者的定植研究的强大历史基础上 肺炎球菌，新型七价结合肺炎球菌疫苗对鼻咽部的影响 具体涉及抗生素敏感性和远离疫苗血清型的携带者正在 学习。这些研究也可能对持续青霉素预防这种疾病的有效性有影响。 高危人群。这项研究的所有队列已经完全登记，现在将在下一次跟踪调查 授权期。利用基因芯片研究目前收集到的菌株的基因组含量 表明成为侵袭性肺炎球菌携带一组特定的基因，最明显的是与 铁制交通工具。这一特性将在整个临床菌株队列中进行检查，并研究 该基因座的致病功能将通过突变分析和表型来确定。 在第一个赠款周期中建立小鼠模型。

Patients with sickle cell disease experience a 400 fold increased risk of severe pneumococcal infection. This risk is not shared by other encapsulated pathogens or by other anemias suggesting that there is a potentially causal relationship between severity of pneumococcal disease and the SS phenotype. This application seeks to investigate two aspects of pneumococcal infection in sickle cell disease. Over the previous grant cycle, a collaboration between the program in pneumococcal pathogenesis and the SS transplant mouse model has revealed the PAF receptor to be a key determinant of increased invasive disease. Specific receptor antagonists improve the outcome of disease. This provides a model to examine the bacterial and host determinants of severe disease to be studied in the next grant period. Building on a strong history of this Center's study of the colonization of SS patients with antibiotic resistant pneumococci, the effect of the new seven-valent conjugate pneumococcal vaccine on nasopharyngeal carriage with specific reference to antibiotic susceptibility and shifts away from vaccine serotypes is being studied. These studies may also have implications for the efficacy of continued penicillin prophylaxis in this at risk population. All cohorts for the study have been fully enrolled and will now be followed for the next grant period. Investigation of the genomic content of strains collected thusfar using microarrays has indicated that SS pneumococci that become invasive carry a specific set of genes, most notably related to iron transport. This property will be examined in the entire clinical cohort of strains and the relationship of the function of the locus to pathogenesis will be determined by mutational analysis and phenotype in the mouse model established in the first grant cycle.