Gene expression in epithelial cells in response to pneumovirus infection

Respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM) are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR) and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner

Inflammatory responses to acute pneumovirus infection in neonatal mice

Background: The innate immune responses of neonates differ dramatically from those of adults. Here we examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection. Results: We demonstrate that virus replication proceeds indistinguishably in all age groups (inoculated at 1, 2, 3 and 4 weeks of age), although inflammatory responses vary in extent and character. Some of the biochemical mediators detected varied minimally with age at inoculation. Most of the mediators evaluated demonstrated elevated expression over baseline correlating directly with age at the time of virus inoculation. Among the latter group are CCL2, CCL3, and IFN-γ, all cytokines previously associated with PVM-induced inflammatory pathology in mature mice. Likewise, we detect neutrophil recruitment to lung tissue in all age groups, but recruitment is most pronounced among the older (3 - 4 week old) mice. Interestingly, all mice exhibit failure to thrive, lagging in expected weight gain for given age, including the youngest mice that present little overt evidence of inflammation. Conclusions: Our findings among the youngest mice may explain in part the phenomenon of atypical or minimally symptomatic respiratory infections in human neonates, which may be explored further with this infection model

Efficient replication of pneumonia virus of mice (PVM) in a mouse macrophage cell line

Pneumonia virus of mice (PVM; family Paramyxoviridae, subfamily Pneumovirinae) is a natural respiratory pathogen of rodent species and an important new model for the study of severe viral bronchiolitis and pneumonia. However, despite high virus titers typically detected in infected mouse lung tissue in vivo, cell lines used routinely for virus propagation in vitro are not highly susceptible to PVM infection. We have evaluated several rodent and primate cell lines for susceptibility to PVM infection, and detected highest virus titers from infection of the mouse monocyte-macrophage RAW 264.7 cell line. Additionally, virus replication in RAW 264.7 cells induces the synthesis and secretion of proinflammatory cytokines relevant to respiratory virus disease, including tumor necrosis factor-α (TNF-α), interferon-β (IFN-β), macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) and the functional homolog of human IL-8, mouse macrophage inflammatory peptide-2 (MIP-2). Identification and characterization of a rodent cell line that supports the replication of PVM and induces the synthesis of disease-related proinflammatory mediators will facilitate studies of molecular mechanisms of viral pathogenesis that will complement and expand on findings from mouse model systems

A quality improvement education initiative to increase adolescent human papillomavirus (HPV) vaccine completion rates

HPV vaccine uptake is low, nationwide. Quality improvement (QI) principles have the potential to change practice; however, not all providers are confident with QI skills. We developed an educational program designed to enhance QI skills and improve HPV vaccination rates. Five pediatric practices participated in the pilot initiative. Training consisted of presentations regarding QI methods, data tracking and analysis, and system changes to reduce missed opportunities. Monthly for 6 months, participants performed chart audits, captured data, printed run charts, and developed, implemented, and tracked interventions. Outcome measures included rates of HPV vaccine completion and missed opportunities. A second phase included eight different pediatric practices who received similar training. Outcome measures included rates of HPV vaccine initiation and completion. Over the 6 months, mean HPV vaccine completion rates increased (45% to 65%) and missed opportunities for HPV vaccination decreased (45% to 19%) in the pilot program. When the program was replicated in phase 2, an increase was seen in both HPV vaccine initiation (46% to 61%) and completion (62% to 94%) rates. Combining QI education with workflow-focused strategies was associated with a reduction in missed opportunities and a substantial increase in HPV vaccine completion rates

Multi-component cancer prevention awareness program to improve adolescent HPV vaccine uptake

Objective We introduced a multi-component cancer prevention awareness program to primary care practices across New York State to evaluate its impact on adolescent human papillomavirus (HPV) vaccination rates. Methods Eight pediatric and three family medicine practices were recruited to participate in this program. On-site training sessions were provided for all practice providers and staff to discuss the importance of HPV vaccine and cancer prevention and teach strategies for delivering a strong vaccine recommendation. Each practice received a study-specific booklet that included HPV vaccine information and other commonly provided cancer prevention guidance. These booklets were distributed to all adolescents and their parents during well visits over a one-year period. Practice specific and county-wide HPV vaccination rates were assessed before and 12 months after the program training session. Results One year after program initiation, aggregate data show statistically higher vaccine series initiation rates among 11–12 and 13–18-year-olds and higher vaccine series completion rates among 13–18-year-olds. The greatest and most consistent improvements were seen in vaccine initiation rates for the 11–12-year-old cohort. Disparities in vaccine uptake were observed by gender and medical specialty. Conclusion Cancer prevention education targeting providers, office staff, patients, and parents, improved adolescent HPV vaccine series initiation rates

Immunization attitudes and practices among family medicine providers

Objective: To describe immunization attitudes and practices among family medicine providers across New York State. Methods: In this cross-sectional survey study, family medicine providers across New York State completed a questionnaire to assess vaccine beliefs and barriers and immunization practices. Statistical analysis: Descriptive statistical methods were used to define provider characteristics, knowledge and vaccine practices. Results: Completed questionnaires from 226 family medicine providers were included for analysis. As a group, 207/218 (95%) of providers who answered the question state they always recommend standard pediatric vaccines. Of the 209 providers who answered both questions, 47 (22%) state they always recommend standard pediatric vaccines but do not always recommend HPV vaccine to eligible 11–12 year-old patients. Only 75% of providers strongly disagreed with the statement ‘vaccinating adolescents against HPV increases the likelihood of unprotected sex'. Even though 178/190 (94%) and 164/188 (87%) of surveyed family medicine providers reported recommending that their pregnant patients receive influenza vaccine and Tdap vaccine, respectively, only 134/185 (72%) routinely do so in their office. Conclusion: Most family medicine providers self-report always recommending standard pediatric vaccines, however only a minority are following ACIP recommendations. Educational sessions to update family medicine providers on ACIP recommendations and address individual provider concerns may improve provider vaccine confidence and uptake of vaccines by their patients