Over the last century, major advances in the prevention and treatment of infections due to Streptococcus pneumoniae have been attributed to the development of antimicrobial drugs and polysaccharide vaccines. Yet, the emergence of antimicrobial drug resistance and, more recently, non-vaccine serotypes among clinical isolates of S. pneumoniae seriously threaten the effectiveness of these interventions. Critical to the successful implementation of prevention and treatment strategies for pneumococcal infections has been the availability of epidemiological data identifying high risk populations for infection as appropriate targets for vaccination or antimicrobial chemotherapy. However, risk factor identification at the individual level may no longer be adequate for controlling and preventing infectious diseases that spread rapidly across complex human networks. For example, it is clear that the transmission of S. pneumoniae involves both host and environmental factors. Relevant environmental factors include characteristics of both the natural (eg, climate) and built (eg, housing density, child care centers) environment. However, neighborhood characteristics that might influence the transmission of bacteria within urban environments are poorly understood because past studies examining neighborhood-level risk factors for pneumococcal carriage have focused on relatively isolated, geographically distinct communities. The significance of these findings for infection control and prevention in urban settings is unknown. Preliminary data indicate that the incidence of pneumococcal bacteremia displays significant small area heterogeneity suggesting the hypothesis that neighborhood characteristics influence pneumococcal transmission rates within urban settings. To test this exploratory hypothesis, we will take advantage of a recently established large primary care pediatric network to sample children from neighborhoods across a major U.S. city in order to obtain measures of patterns of pneumococcal carriage. The primary aim is to demonstrate that neighborhood level characteristics, specifically measures of child day care attendance and crowding, are risk factors for pneumococcal carriage independent of individual host characteristics. The study will be a cross-sectional assessment of patterns of pneumococcal carriage among children living in Philadelphia sampled from six geographically diverse pediatric practices within an integrated network of primary care sites. We will obtain demographic, clinical, and especially, geographic data on all enrollees and obtain nasal swabs to characterize the pneumococcal carriage status of all study subjects. In addition, serological typing of all isolates will permit separate analyses for geographic heterogeneity within serotype subgroups. Individual level characteristics that may influence pneumococcal carriage will be extracted from the integrated electronic medical record. Data on neighborhood-level factors will be available from the University of Pennsylvania Cartographic Modeling Laboratory. Multi-level modeling approaches will be employed to examine the individual and neighborhood-level factors associated with pneumococcal carriage.
Effective vaccination and infection control procedures require an understanding of risk factors for infectious disease transmission. Using carriage of S. pneumoniae among children as a model, this study will examine neighborhood factors that influence transmission and could become targets for future vaccination and infection control interventions to reduce the burden of pneumococcal disease, and, by extension, other respiratory pathogens. ? ? ? ? ?
| Pettigrew, Melinda M; Laufer, Alison S; Gent, Janneane F et al. (2012) Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children. Appl Environ Microbiol 78:6262-70 |
| Laufer, Alison S; Metlay, Joshua P; Gent, Janneane F et al. (2011) Microbial communities of the upper respiratory tract and otitis media in children. MBio 2:e00245-10 |
| Adams, Kristin N; Takaki, Kevin; Connolly, Lynn E et al. (2011) Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell 145:39-53 |
