HPV vaccine knowledge, attitudes, and practices among New York State medical providers, dentists, and pharmacists.

Healthcare provider vaccine knowledge and attitudes influence delivery of a strong vaccine recommendation. We aim to describe HPV vaccine knowledge, attitudes, and recommendation or discussion practices (KAP) among New York State medical providers, dentists, and pharmacists. A survey to assess providers' KAP was distributed electronically to NYS members of medical organizations. Descriptive and inferential statistical methods were used to characterize provider KAP. Responses from 1637 surveys were included, from 864 (53%) medical providers, 737 (45%) dentists, and 36 (2%) pharmacists. 59% (509/864) of medical providers responded that they recommend HPV vaccine to patients, with 390/509 (77%) strongly recommending vaccine at 11-12 years. Medical providers were more likely to report recommending HPV vaccine for children ages 11-12 years if they strongly agreed that HPV vaccine prevents cancer 326/391 (83%) vs 64/117 (55%) and responded that HPV vaccination does not increase the risk of unprotected sex (386/494 (78%) vs 4/15 (25%)) (p < .05). Less than 1/3 of dentists reported discussing HPV vaccine with 11-26-year-old females (230/737, 31%) and males (205/737, 28%) at least "sometimes." Dentists were more likely to answer that they routinely discuss HPV vaccine with children ages 11-12 years if they responded that HPV vaccination does not increase sexual activity (70/73 (96%) vs 528/662 (80%), p < .001). Few pharmacists reported discussing HPV vaccine with 11-26-year-old females (6/36 (17%)) and males (5/36 (14%)) at least "sometimes." Gaps in HPV vaccine knowledge among providers still exist and may influence vaccine attitudes and recommendation or discussion practices.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus (RSV) Vaccine in Healthy RSV-Seropositive Children 12-23 Months of Age.

BACKGROUND: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12-23-month-old RSV-seropositive children followed up for 2 years after vaccination. METHODS: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti-RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2. RESULTS: Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1. CONCLUSIONS: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. CLINICAL TRIALS REGISTRATION: NCT02927873.

Respiratory syncytial virus (RSV) is among the main causes of bronchiolitis and pneumonia regularly leading to hospitalization in children. A safe and effective vaccine to prevent RSV infection in this age group has not yet been found, despite great efforts over several decades. This study tested a new candidate RSV vaccine, expressing 3 important pieces of the virus, in toddlers who already had a previous RSV infection. The vaccine was generally well tolerated. Vaccination triggered antibodies against RSV that were able to block the virus in laboratory tests and that persisted for 1 year.

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.

Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose. METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose. RESULTS: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions. CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).

Anaerobic Necrotizing Pneumonia: Another Potential Life-threatening Complication of Vaping?

An adolescent girl with a history of frequent electronic cigarette use of nicotine was hospitalized with severe necrotizing pneumonia. Blood cultures obtained before the administration of empirical broad-spectrum intravenous antibiotics had positive results for the growth of Fusobacterium necrophorum The pathogen is an uncommon but well-known cause of anaerobic pneumonia with unique features that are collectively referred to as Lemierre syndrome or postanginal sepsis. The syndrome begins as a pharyngeal infection. Untreated, the infection progresses to involve the ipsilateral internal jugular vein, resulting in septic thrombophlebitis with direct spread from the neck to the lungs causing multifocal necrotizing pneumonia. The teenager we present in this report had neither a preceding pharyngeal infection nor Doppler ultrasonographic evidence for the presence of deep neck vein thrombi, leading us to explore alternative mechanisms for her pneumonia. We propose the possibility that her behavior of frequent vaping led to sufficient pharyngeal irritation such that F necrophorum colonizing her oropharynx was inhaled directly into her lungs during electronic cigarette use. Preexisting, but not yet recognized, vaping-related lung injury may have also contributed to her risk of developing the infection. The patient was hospitalized for 10 days. At follow-up one month later, she still became short of breath with minimal exertion.

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.

Associations between population based voting trends during the 2016 US presidential election and adolescent vaccination rates.

BACKGROUND: Politics play a role in the dissemination of public health information, including immunization-related issues. We aim to describe relationships between HPV vaccination rates and state voting patterns during the 2016 US presidential election. METHODS: We classified each of the 50 states as either "Red" or "Blue," based on whether a higher proportion of the state's casted votes were for the Republican or Democratic nominee during the 2016 US presidential election. State-specific HPV, Tdap, and meningococcal vaccination rates were obtained from the 2016-National Immunization Survey-Teen. State socio-demographic factors and HPV vaccine legislation were obtained from the US Census Bureau and National Conference of State Legislatures. Vaccination rates and socio-demographic variables were compared using independent t-tests. Multiple linear regression compared vaccination rates between "Red" and "Blue" states, adjusting for percentage of both uninsured children and educational attainment. RESULTS: Compared to "Blue" states, "Red" states had significantly lower unadjusted HPV vaccine series initiation (56% vs 66%, p < 0.05) and completion (39% vs 50%, p < 0.05) rates; yet had similar rates of Tdap (88% vs 89%, p > 0.05) and meningococcal (79% vs 83%, p > 0.05) vaccinations. After adjusting for potential confounders, the regression-adjusted mean rate for HPV vaccine initiation and completion remained significantly lower for "Red" states compared to "Blue" states (57% vs 65%, p < 0.05, and 41% vs 48%, p < 0.05, respectively). CONCLUSION: HPV vaccination rates are associated with statewide-level voting patterns. Future interventions aimed at improving HPV vaccination rates should consider engaging local and national elected leaders to be proactive in disseminating accurate and authoritative immunization information.

Cancer Prevention Education for Providers, Staff, Parents, and Teens Improves Adolescent Human Papillomavirus Immunization Rates.

OBJECTIVE: To develop a program to educate providers, office staff, patients, and parents on life-long cancer prevention strategies, including the use of human papillomavirus (HPV) vaccine to improve adolescent HPV vaccination rates. STUDY DESIGN: A 2-phase program was implemented at 6 pediatric practices across upstate New York. Phase 1 included provider and staff education regarding practice-specific vaccination challenges and discussion of the contents of a study-specific cancer-prevention booklet, which included HPV vaccine information. Throughout phase 2, the booklets were distributed to all adolescents and their parents during office visits over a 12-month period. Practice-specific, countywide, and statewide HPV vaccination rates were assessed before phase 1, and 6 and 12 months after the launch of phase 2. RESULTS: One year after implementing phase 2 in 6 practices, adolescent HPV vaccine series initiation increased by at least 10% in 3 practices, and at least 5% in 5 practices. Similarly, adolescent vaccine series completion rates increased by more than 10% in 3 practices. The percent change in vaccine series completion rates across all study sites postintervention ranged from 12% to 20% for 11- to 12-year-olds, and from 7% to 23% for 13- to 18-year-olds. CONCLUSIONS: Cancer prevention education targeting providers, office staff, patients, and parents was modestly effective for improving adolescent HPV vaccination rates.

Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants.

BACKGROUND: MEDI8897 is a recombinant human monoclonal antibody being developed for prophylaxis of serious respiratory syncytial virus (RSV) disease in all infants. METHODS: In this phase 1b/2a dose-escalation study, healthy preterm infants with a gestational age of 32-35 weeks were randomized to receive a single intramuscular injection of MEDI8897 (10, 25 or 50 mg) or placebo. Safety, pharmacokinetics, RSV-neutralizing antibody and antidrug antibody (ADA) assessments were performed during the 360-day follow-up period. Infants who experienced medically attended lower respiratory tract infections (LRTIs) were tested for RSV. RESULTS: MEDI8897 serum half-life ranged from 62.5-72.9 days. On day 151, 87% of infants in the 50 mg group had serum concentrations above the 90% effective concentration target level of 6.8 µg/mL, and 90% showed a ≥4-fold rise from baseline in serum RSV-neutralizing antibody levels. Adverse events (AEs) were reported in 17 of 18 (94.4%) placebo and 66 of 71 (93.0%) MEDI8897 recipients. Three MEDI8897 recipients experienced 5 serious AEs (3 LRTIs, 2 febrile seizures). ADA was detected at any time postbaseline in 28.2% of MEDI8897 recipients and at day 361 only in 26.5% of subjects. ADA response was not associated with AEs. Five (7%) MEDI8897 recipients experienced medically attended LRTIs through day 150; 1 tested positive for RSV (10 mg group). CONCLUSIONS: MEDI8897 had a favorable safety profile in healthy preterm infants. The extended half-life of MEDI8897 and demonstrated RSV-neutralizing activity support protection from RSV for the duration of a typical 5-month season after a single 50 mg intramuscular (IM) dose.

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.

Student HPV vaccine attitudes and vaccine completion by education level.

PURPOSE: We describe HPV vaccine attitudes among students of different education levels. METHODS: High school, college, and graduate-level health care professional students were surveyed regarding HPV vaccine knowledge, attitudes, and receipt. Relationships between categorical variables were analyzed using chi-square tests of independence and z-tests for proportions. Means for quantitative variables were compared using t-tests and one-way analysis of variance. RESULTS: 57% and 42% of the 889 students reported starting and completing HPV vaccine series, respectively, with no statistical difference by education level. 61% of students who reported receiving a provider recommendation had completed the series, compared to 6% of those who did not receive recommendation (p<0.001). The belief that HPV vaccine prevents cancer was strongly associated with vaccine completion (p=0.003). CONCLUSION: HPV vaccine coverage rates remain suboptimal. Future interventions should focus on improving provider recommendation and patient belief that HPV vaccine prevents cancer.

Pediatric provider vaccine hesitancy: An under-recognized obstacle to immunizing children.

OBJECTIVE: To describe vaccine attitudes among pediatric healthcare providers attending immunization conferences. STUDY DESIGN: Attendees of 5 American Academy of Pediatrics (AAP)-sponsored vaccine conferences held between June and November 2013 anonymously completed a questionnaire assessing vaccine attitudes and practices prior to the opening of educational sessions. Pearson's chi-square tests and Fisher's exact tests were used to analyze associations between vaccine attitudes, vaccine practices and provider characteristics. RESULTS: 680 providers attending AAP-sponsored vaccine conferences were included. 661/666 (99%) enrolled providers state they routinely recommend standard pediatric vaccines, yet, 30 (5%) state that they do not routinely recommend influenza and/or human papillomavirus (HPV) vaccines. These providers expressed vaccine safety (87/680 (13%)) and efficacy (21/680 (31%)) concerns and stated belief in vaccine misperceptions: vaccine causes autism (34/668, 5%), multiple vaccines at a single visit reduces vaccine efficacy (43/680, 6%) or overwhelms the immune system (63/680, 9%), and administering HPV vaccine will increase the likelihood of unprotected adolescent sexual activity (29/680, 4%). Six percent of providers who do not routinely recommend all pediatric vaccines correctly identified themselves as vaccine hesitant. CONCLUSION: Vaccine hesitancy is under-recognized among pediatric providers attending AAP-sponsored immunization conferences. Educational interventions tailored to address provider vaccine concerns are needed to improve provider vaccine confidence.

Adolescent immunization: 2015 and beyond.

In the last decade, the approach to adolescent immunizations has changed substantially. At ages 11 or 12 years, routine administration of four vaccines-a tetanus, diphtheria, pertussis (Tdap) booster, the first of two doses of quadrivalent conjugate meningococcal vaccine (MCV4), a three-dose series of human papillomavirus (HPV) vaccine, and an annual influenza vaccine-are now recommended. Vaccine uptake is easily tracked in the office setting using electronic medical records, whereas national data for teens have been tracked through the National Immunization Survey-Teen (NIS-teen) since 2005. In 2013, NIS-teen demonstrated that Tdap and MCV4 uptake are robust, whereas HPV vaccine coverage lags behind substantially. Efforts to improve immunization coverage rates among adolescents should continue, especially as new vaccines are becoming available for use in this age group. Several changes in the current approach to teen vaccination are expected to emerge in 2015.

Novel inflammatory markers, clinical risk factors and virus type associated with severe respiratory syncytial virus infection.

BACKGROUND: Virus-induced inflammation contributes to respiratory syncytial virus (RSV) pathogenesis. We sought to determine the specific mediators that are associated with more severe illness in young children. METHODS: Children ≤ 5 years of age seen in our emergency department for respiratory symptoms from September 1998 to May 2008 were eligible for enrollment. Nasopharyngeal wash samples were collected from all eligible patients, and clinical data were recorded. Individuals were included in this study if nasopharyngeal wash samples were positive for RSV only. Patients enrolled in the study were stratified by disease severity, defined as mild (not hospitalized), moderate (hospitalized) or severe (requiring intensive care unit stay). Concentrations of individual inflammatory biomarkers in nasopharyngeal wash fluids were determined using the Luminex human 30-plex assay. RESULTS: Eight hundred fifty-one patients met study criteria: 268 (31.5%) with mild, 503 (59.1%) with moderate and 80 (9.4%) with severe illness. As expected, illness severity was directly associated with young age, prematurity, heart or lung disease, infection with RSV group A and elevated concentrations of interleukin (IL)-2R, IL-6, CXCL8, tumor necrosis factor-α, interferon-α, CCL3, CCL4 and CCL2. In addition, we report several novel and mechanistically important inflammatory biomarkers of severe RSV disease, including IL-1ß, IL1-RA, IL-7, epidermal growth factor and hepatocyte growth factor. CONCLUSIONS: In a large, longitudinal study (10 years, 851 enrolled patients) limited to RSV infection only, in which well-known risk factors are confirmed, we identified 5 novel biomarkers specifically of severe disease. These markers may ultimately serve to elucidate disease mechanisms.

Unrecognized viral respiratory tract infections in premature infants during their birth hospitalization: a prospective surveillance study in two neonatal intensive care units.

OBJECTIVE: To determine the frequency and effects of nosocomial respiratory viral infections (RVIs) in premature neonates, including those who may be asymptomatic. STUDY DESIGN: We performed a year-long surveillance for RVIs in infants <33 weeks gestational age admitted to 2 Syracuse neonatal intensive care units. Infants were enrolled within 3 days of neonatal intensive care unit admission and were sampled for RVIs until discharge using a multiplex polymerase chain reaction assay capable of detecting 17 different respiratory viruses or subtypes. RESULTS: Twenty-six of 50 prematurely born infants (52%) tested positive for a respiratory virus at least once during their birth hospitalization. Testing positive for a respiratory virus was significantly associated with longer length of stay (70 days vs 35 days, P = .002) and prolonged ventilatory support (51 vs 13 days, P = .002). Infants who tested positive for a respiratory virus during their birth hospitalization had more than twice the rate of developing bronchopulmonary dysplasia (P < .05). CONCLUSION: Nosocomial RVIs were frequent in our study population, despite the absence of clinical indicators of illness. Length of hospital stay was significantly longer and a diagnosis of bronchopulmonary dysplasia was more common in infants who had respiratory viruses detected.

IL-21 promotes the pathologic immune response to pneumovirus infection.

IL-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of B cells, increased Ig production, and the development of Th17 and T follicular helper cells. IL-21 is also implicated in the development of autoimmune disease and has antitumor activity. In this study, we investigated the role of IL-21 in host defense to pneumonia virus of mice (PVM), which initiates an infection in mice resembling that of respiratory syncytial virus disease in humans. We found that PVM-infected mice expressed IL-21 in lung CD4(+) T cells. Following infection, Il21r(-/-) mice exhibited less lung infiltration by neutrophils than did wild-type (WT) mice and correspondingly had lower levels of the chemokine CXCL1 in bronchoalveolar lavage fluid and lung parenchyma. CD8(+), CD4(+), and γδ T cell numbers were also lower in the lungs of PVM-infected Il21r(-/-) mice than in infected WT mice, with normal Th17 cytokines but diminished IL-6 production in PVM-infected Il21r(-/-) mice. Strikingly, Il21r(-/-) mice had enhanced survival following PVM infection, and moreover, treatment of WT mice with soluble IL-21R-Fc fusion protein enhanced their survival. These data reveal that IL-21 promotes the pathogenic inflammatory effect of PVM and indicate that manipulating IL-21 signaling may represent an immunomodulatory strategy for controlling PVM and potentially other respiratory virus infections.

Eosinophilia and the seroprevalence of schistosomiasis and strongyloidiasis in newly arrived pediatric refugees: an examination of Centers for Disease Control and Prevention screening guidelines.

The US Centers for Disease Control and Prevention has published refugee health guidelines that recommend examination of the absolute eosinophil count (AEC) to screen for asymptomatic schistosomiasis and strongyloidiasis. We examined the predictive validity of an AEC >400 cells/microL to identify refugees with serologic evidence for schistosomiasis or strongyloidiasis. Our study revealed that eosinophilia was not predictive of serologic evidence of either a Schistosoma species or Strongyloides stercoralis infection in the pediatric refugees examined in this study.

Clinical features, adenovirus types, and local production of inflammatory mediators in adenovirus infections.

BACKGROUND: Adenovirus infection manifests in many ways, with respiratory and gastrointestinal symptoms predominating. METHODS: We performed a retrospective chart review on children evaluated at our center who had a nasal wash culture positive for adenovirus. Archived nasal washes were retrieved. Polymerase chain reaction for 15 respiratory viruses was performed on these samples. Patients who were coinfected with another virus were excluded. Adenovirus typing was performed using polymerase chain reaction primers directed at the conserved hexon gene. Bead proteomics was used to measure concentrations of inflammatory mediators. RESULTS: Seventy-eight patients were infected only with adenovirus. The clinical diagnosis was upper respiratory infection in 60%, pneumonia in 18%, febrile seizure in 8%, and bronchiolitis in 6%. Subgroup-C and B1 infections were most common. Seventy percent of patients with upper respiratory infection and all 5 patients with bronchiolitis had a subgroup-C infection; pneumonia was caused by subgroup-B1 and C viruses. Compared with asymptomatic control patients, adenovirus infected patients had higher nasal wash concentrations of interleukin (IL)-1alpha, IL-6, inducible protein-10, macrophage inflammatory protein-1alpha, tumor necrosis factor alpha, monokine induced by gamma interferon, and interferon-alpha (P < 0.05). In addition, we found that IL-8 and IL-1alpha (P < 0.05) were higher in the nasal washes obtained from hospitalized patients than in nonhospitalized patients. CONCLUSIONS: Adenovirus infection causes an array of clinical disease and is associated with local production of several proinflammatory cytokines. The observation that nasal wash IL-8 and IL-1alpha concentrations were higher in patients requiring hospitalization suggests that these mediators contribute to disease severity.

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-alpha (TNF-alpha), interferon-beta (IFN-beta), macrophage inflammatory proteins 1alpha and 1beta (MIP-1alpha and MIP-1beta) 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.

Mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and interferon-gamma receptor deficient mice.

Protective mechanisms underlying the responses to mucosal vaccination are not yet clearly defined. Using the natural mouse pneumovirus pathogen, pneumonia virus of mice (PVM), we explore responses of wild type and interferon-gamma (IFNgamma) receptor gene-deleted mice to virulent challenge after mucosal vaccination with an attenuated virus strain. Serum neutralizing antibodies develop after intranasal inoculation with 30 pfu of attenuated, replication-competent PVM strain 15, which correlate with diminished gross and microscopic pulmonary pathology and protection from weight loss in response to subsequent challenge with the virulent parent PVM strain J3666. Virus replication in response to challenge was blunted in PVM strain 15 vaccinated mice, as was local production of secretory mediators IFNgamma, TNF-alpha, MIP-1 alpha, and MIP-2. Interestingly, responses of vaccinated IFNgamma receptor gene-deleted mice were indistinguishable from those of the wild type, suggesting that IFNgamma signaling may not be crucial for the generation of adaptive responses to pneumovirus infection in vivo.