Oral GS-5806 activity in a respiratory syncytial virus challenge study.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of infant hospitalizations and is increasingly recognized as a cause of considerable morbidity and mortality. No accepted antiviral treatment exists. METHODS: We conducted a double-blind, placebo-controlled study of GS-5806, an oral RSV-entry inhibitor, in healthy adults who received a clinical challenge strain of RSV intranasally. Participants were monitored for 12 days. At the time of a positive test for RSV infection or 5 days after inoculation, whichever occurred first, participants were randomly assigned to receive GS-5806 or placebo in one of seven sequential cohorts. Cohorts 1 to 4 received a first dose of 50 mg of GS-5806 and then 25 mg daily for the next 4 days, cohort 5 received a first dose of 50 mg and then 25 mg daily for the next 2 days, cohort 6 received one 100-mg dose, and cohort 7 received a first dose of 10 mg and then 5 mg daily for the next 4 days. Dose selection for cohorts 5, 6, and 7 occurred after an interim analysis of data for cohorts 1 to 4. The primary end point was the area under the curve (AUC) for the viral load, which was assessed after administration of the first dose through the 12th day after inoculation. Secondary end points were mucus weight and symptom scores. RESULTS: Among the 54 participants in cohorts 1 to 4 who were infected with RSV, active treatment was associated with a lower viral load (adjusted mean, 250.7 vs. 757.7 log10 plaque-forming-unit equivalents [PFUe] × hours per milliliter; P<0.001), lower total mucus weight (mean, 6.9 g vs. 15.1 g; P=0.03), and a lower AUC for the change from baseline in symptom scores (adjusted mean, -20.2 vs. 204.9 × hours; P=0.005). The results were similar in cohorts 5, 6, and 7. Adverse events, including low neutrophil counts and increased levels of alanine aminotransferase, were more common among participants receiving GS-5806. CONCLUSIONS: Treatment with GS-5806 reduced the viral load and the severity of clinical disease in a challenge study of healthy adults. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01756482.).

Factors associated with in-office influenza vaccination by U.S. pediatric providers.

BACKGROUND: In the United States, influenza vaccination is recommended for all children 6 months and older; however, vaccination rates are below target levels. A broad sample of U.S. pediatric offices was assessed to determine factors that influence in-office influenza vaccination rates. METHODS: Offices (N = 174) were recruited to participate in an observational study over three influenza seasons (2008-2009, 2009-2010, 2010-2011). Only data from the first year of an office's participation in the study were used. Associations of coverage and 2-dose compliance rates with office characteristics and selected vaccination activities were examined using univariate regression analyses and linear regression analyses using office characteristics identified a priori and vaccination activities with P values ≤ 0.10 in univariate analyses. RESULTS: Influenza vaccination coverage for children 6 months to 18 years of age averaged 25.2% (range: 2.0%-69.1%) and 2-dose compliance for children < 9 years of age averaged 53.4% (range: 5.4%-96.2%). Factors associated with increased coverage were non-rural site (P = 0.025), smaller office size (fewer than 5000 patients; P < 0.001), use of evening and weekend hours to offer influenza vaccine (P = 0.004), a longer vaccination period (P = 0.014), and a greater influenza vaccine coverage rate among office staff (P = 0.012). Increased 2-dose compliance was associated with smaller office size (P = 0.001) and using patient reminders (P = 0.012) and negatively related to use of electronic provider reminders to vaccinate (P = 0.003). CONCLUSIONS: To maximize influenza vaccine coverage and compliance, offices could offer the vaccine during evening and weekend hours, extend the duration of vaccine availability, encourage staff vaccination, and remind patients that influenza vaccination is due. Additional efforts may be required in large offices and those in rural locations.

Clinical guidance on the use of live attenuated influenza vaccine after inadvertent freezing and warming.

The immediate and long-term impact of temperature deviations that may occur in clinical practice on live attenuated influenza vaccine (LAIV) potency was examined in four distinct studies that exposed vaccine to freeze/thaw cycles, warming, and heating conditions. No significant loss of vaccine potency was observed after three freeze/thaw cycles, warming of vaccine to 15°C (59°F) for 72 hours or less, exposure to room temperature (25°C/77°F) for 12 hours or less, or after heating to 37°C (99°F) for 6 hours or less. The results of these studies demonstrate that LAIV potency can potentially be maintained after exposure to temperature deviations. If a particular annual formulation of LAIV is exposed to temperatures outside of the recommended storage range, practitioners should contact the manufacturer for guidance regarding proper vaccine handling.

Influenza vaccination of parents and guardians by US pediatricians.

In the 2008-2009 and 2009-2010 influenza seasons, 84 pediatric offices participating in a prospective observational study were surveyed about whether the office offered influenza vaccine to parents and guardians of pediatric patients. Each season, approximately half of all offices cited offering seasonal influenza vaccine to parents. In 2008-2009, reported barriers to parental vaccination included reimbursement, medicolegal concerns, and logistics. In 2009-2010, 51% of offices (n = 43) administered one parental seasonal vaccination for every 29 pediatric seasonal vaccinations and one parental H1N1 vaccination for every 23 pediatric H1N1 vaccinations. Currently, the number of parental vaccinations per office is small but parental vaccination by pediatricians may increase in the future given the new recommendations that all adults 18 to 49 years of age should be vaccinated annually. Efforts should be taken to address barriers to parental vaccination so that pediatricians are better able to vaccinate parents/guardians of their patients against influenza.

Impact of a pediatric primary care office-based mock code program on physician and staff confidence to perform life-saving skills.

BACKGROUND: Previous studies have described that pediatric offices are ill-prepared for medical emergencies. Pediatric "mock codes" have been utilized to increase the emergency preparedness of inpatient medical units for several decades. These practice drills have been shown to both increase practitioners' confidence and decrease anxiety during actual resuscitations. Although the use of mock codes is recommended in the outpatient setting, these benefits have yet to be demonstrated for office-based practitioners. OBJECTIVE: We conducted this study to determine whether mock codes performed in pediatric primary care offices increase practitioner confidence to perform life-saving skills. METHODS: Pediatric group practices participated in a clinical trial of an office-based, 2-step, emergency preparedness training. First, physicians and staffs attended a 1-hour didactic program which included staff education, office emergency protocols, emergency equipment and medications, and guidelines on instituting a mock code program. Second, each practice participated in a 10-15-minute mock code exercise. The drill was conducted by pediatric advanced life support instructors. After the code, a 30-minute feedback session was conducted which reviewed office coordination, individual skill performance, and approach to resuscitation. Each participating practice also received an infant manikin and a text complete with several mock codes scenarios written specifically for the pediatric primary care office. Evaluation of the intervention consisted of 2 components. (1) Pre- and postintervention completion of a self-administered survey assessed participants' comfort in emergency situations and confidence to perform specific life-saving skills, using an ordinal scale: 1 = "strongly agree" to 5 = "strongly disagree". (2) Practices were contacted by telephone 12 months after the training to determine whether they had implemented improvements in emergency preparedness, including instituting mock codes, preparing a written emergency protocol and purchasing new emergency equipment and medications. RESULTS: Eleven group pediatric practices participated, which were representative of urban, suburban, and rural offices in southwestern Pennsylvania. Ninety-seven of a total 164 (59%) physicians and staff members completed both pre- and postintervention surveys. Practitioner participants were analyzed in 2 groups. Group 1 consisted of physicians, nurse practitioners, and physician assistants; group 2 consisted of registered nurses, licensed practical nurses, and medical assistants. Comparison of pre- versus postintervention surveys in both of these groups revealed significant improvement in reported confidence to perform resuscitation skills that were included in the mock code after the training: airway positioning (group 1, 67% vs. 94%, P < 0.001; group 2, 55% vs. 75%, P = 0.003), airway suctioning, (group 1, 64% vs. 88%, P = 0.005; group 2, 27% vs. 51%, P < 0.001), and bag-mask assisted ventilation (group 1, 82% vs. 91%, P = 0.003; group 2, 39% vs. 71%, P < 0.001). In addition, group 1 reported more confidence in their ability to place an intraossesous line (24% vs. 39%, P = 0.003) and group 2 showed a significant increase in their confidence to administer oxygen (65% vs. 84%, P < 0.001). As a result of the mock code, 83% of all participants, both medical and nonmedical staffs, and 96% of physicians felt less anxious about medical emergencies in the office. Twelve months after the conclusion of the program, 18% of offices had conducted 1 or more mock codes, 64% of offices had written an emergency protocol, and 27% of offices had acquired essential resuscitation medications or equipment. CONCLUSIONS: The results of this study support the recommendation that mock codes should be performed in the pediatric primary care setting to improve practitioner confidence and decrease practitioner anxiety.

Improved timing of availability and administration of influenza vaccine through the US Vaccines for Children Program from 2007 to 2011.

The Vaccines for Children (VFC) program distributes one half of all vaccines administered to US children. Compared with commercial vaccine distribution, VFC distribution is more complex. This prospective observational study compares the delivery and administration of VFC versus non-VFC influenza vaccine in US pediatricians' offices across 3 influenza seasons and its apparent impact on 2-dose compliance rates. Because of earlier shipping (mean = 29-42 days) of non-VFC vaccines, administration of VFC vaccines was delayed relative to non-VFC vaccines by approximately 1 month in 2007-2008 and 2008-2009 and 2 weeks in 2010-2011. Two-dose compliance rates for the VFC and non-VFC populations were 38.5% and 47.5% (P < .001) in 2007-2008, 45.9% and 55.1% (P < .001) in 2008-2009, and 50.0% and 52.9% (P < .001) in 2010-2011, respectively. Despite delays, earlier VFC shipment in 2010-2011 enabled greater equity in 2-dose compliance.

Effectiveness of intranasal live attenuated influenza vaccine against all-cause acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a frequent complication of influenza in children, and influenza vaccination helps protect against influenza-associated AOM. A live attenuated influenza vaccine (LAIV) approved for eligible children aged ≥2 years for the prevention of influenza also effectively reduces influenza-associated AOM. However, the annual effectiveness of LAIV against all-cause AOM is unknown. METHODS: AOM rates in children aged 6-83 months from 6 randomized, placebo-controlled trials and 2 randomized, inactivated influenza vaccine-controlled trials were pooled and analyzed. To enable comparison with studies of AOM prevention by pneumococcal conjugate vaccines, 12-month effectiveness was calculated assuming that LAIV had no effect outside of influenza seasons. RESULTS: During influenza seasons, LAIV efficacy compared with placebo against all-cause AOM in children aged 6-71 months (N = 9497) was 12.4% (95% confidence interval [CI]: 2.0%, 21.6%) in year 1. In year 2, the efficacy in children aged 18-83 months (N = 4142) was 6.2% (95% CI: -12.4%, 21.7%). Compared with inactivated influenza vaccine, the efficacy of LAIV in children aged 6-71 months (N = 9901) against febrile all-cause AOM was 9.7% (95% CI: -2.1%, 20.1%). The estimated 12-month effectiveness of LAIV compared with placebo against all-cause AOM was 7.5% (95% CI: -2.4%, 16.2%). CONCLUSIONS: LAIV reduced the incidence of all-cause AOM compared with placebo in children. The estimated 12-month effectiveness of LAIV was comparable with 7-valent pneumococcal conjugate vaccine. The effects of the vaccines will overlap somewhat; however, because pneumococcal conjugate vaccines only prevent a fraction of all pneumococcal AOM and influenza-associated AOM can be caused by other pathogens, LAIV could further reduce the incidence of AOM in children.

A postlicensure evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 24-59 months of age.

BACKGROUND: In the United States, live attenuated influenza vaccine (LAIV) was initially approved for use in individuals aged 5-49 years in 2003, which was extended to individuals aged 2-49 years in 2007. At that time, a postlicensure commitment was made to describe the safety of LAIV within a cohort of eligible children aged 2-5 years. METHODS: A prospective observational postmarketing study was conducted to evaluate the safety of LAIV. Rates of medically attended events (MAEs) and serious adverse events (SAEs) in eligible children aged 24-59 months receiving LAIV as part of routine care from October 2007 to March 2010 were compared with rates in a within-cohort self-control, as well as matched unvaccinated and matched trivalent inactivated influenza vaccine (TIV)-vaccinated controls. Children with asthma and other high-risk medical conditions before vaccination were excluded. All MAEs and SAEs through 42 days postvaccination and all hospitalizations and deaths through 6 months postvaccination were analyzed. Statistical significance was declared without multiplicity adjustment. RESULTS: A total of 28,226 unique LAIV recipients were matched with similar numbers of TIV-vaccinated and unvaccinated children. Of 4696 MAE incidence rate comparisons, 83 (1.8%) were statistically significantly higher and 221 (4.7%) were statistically significantly lower in LAIV recipients versus controls. No pattern of MAE rate differences suggested a safety signal with LAIV. Asthma/wheezing MAEs were not statistically increased in LAIV recipients. No anaphylaxis events occurred within 3 days postvaccination. Rates of SAEs were similar between LAIV and control groups. CONCLUSIONS: Results of this postlicensure evaluation of LAIV safety in US children are consistent with preapproval clinical studies and Vaccine Adverse Event Reporting System reports, both of which demonstrated no significant increase in asthma/wheezing events or other adverse outcomes among eligible children aged 24-59 months who received LAIV.

A multi-season national estimate of adult influenza vaccination by U.S. office-based pediatricians, 2006-2011.

There is no national estimate of adult influenza vaccination by U.S. office-based pediatricians. De-identified patient-level data from an electronic healthcare claims database submitted to private and public insurers were analyzed for pediatric offices from the 2006-2007 through 2010-2011 seasons. An average of 321,000 (range: 225,000-434,000) influenza vaccinations per year were estimated to be administered to adults; 52%, 22%, and 26% were given to adults 19-49, 50-64, and ≥65 years of age, respectively. Consistent with the 2010 changes to national guidelines, recommending influenza vaccination of all individuals 6 months of age and older, pediatricians appear to be providing an increasing proportion of adult vaccinations against influenza to adults 19-49 years of age (probably parents of their pediatric patients).

Maternal outcomes among pregnant women receiving live attenuated influenza vaccine.

BACKGROUND: Although the live attenuated influenza vaccine (LAIV) prescribing information contains warnings/precautions against use during pregnancy, administration of LAIV to pregnant women does occur. Data regarding maternal outcomes after LAIV administration during pregnancy are limited. OBJECTIVES: Maternal outcomes after LAIV vaccination during pregnancy were examined. METHODS: Data from a health insurance claims database that covers approximately 50 million individuals were analyzed for the six influenza seasons from 2003-2004 through 2008-2009. Emergency department (ED) visits and hospitalizations occurring within 42 days of vaccination were analyzed by primary diagnosis; outcomes were categorized as cardiopulmonary, obstetric, and other. Cohort characteristics were analyzed using descriptive statistics. RESULTS: Of 834,999 pregnancies identified, 138 (0·017%) were among women who received LAIV vaccinations. Of the 138 pregnant women, 13% were ≤19 years, 67% were 20-34 years, and 20% were ≥35 years of age. Eight events occurred within 42 days of vaccination: one ED visit for bronchitis, two hospitalizations for hyperemesis gravidarum and premature labor, and five ED visits/hospitalizations for common medical conditions. All outcomes identified after LAIV exposure occurred at rates similar to rates in unvaccinated pregnant women reported in the medical literature. CONCLUSIONS: Administration of LAIV to pregnant women is rare; the rate has remained constant since 2004-2005. In this cohort, there was no evidence of significant maternal adverse outcomes after receipt of LAIV. These data may offer some reassurance to providers and pregnant women in the event of inadvertent LAIV administration, but do not support the routine use of LAIV in pregnant women.

A US postmarketing evaluation of the frequency and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years: 2009-2010 season.

The 2007 US approval for use of Ann Arbor strain live attenuated influenza vaccine (LAIV) in children aged 24 through 59 months included precautions against use in (1) children <24 months and children aged 24 through 59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. Results from the third season (2009-2010) of a 3-year study postmarketing commitment to monitor LAIV vaccination rates and frequency of hospitalizations or emergency department visits within 42 days after LAIV are reported here. As in the first 2 seasons, LAIV usage in cohorts 1, 2, and 4 were low relative to those in LAIV-recommended populations. The only numerically increased risk observed was for respiratory events in children aged <24 months administered LAIV, compared to those administered trivalent inactivated influenza vaccine (TIV). The number of children vaccinated with LAIV was small and precluded precise quantification of rare event.

In-office influenza vaccination by US pediatric providers varies greatly and is higher among smaller offices.

During the 2010-2011 US influenza season, 105 pediatric and 13 family practice offices participated in a prospective observational study of in-office influenza vaccination of children. Office characteristics, influenza vaccinations, and vaccination-related activities were reported. Among pediatric offices, first dose vaccination rates (2% to 60%), 2-dose compliance (11% to 100%), the duration of vaccine availability (60-302 days), and office visit type (well vs sick vs clinic) used for vaccinations varied greatly. Pediatric offices had higher vaccination coverage than family practice offices, offered vaccine longer, and administered more vaccinations during sick visits. Smaller offices and higher staff vaccination rates were associated with higher vaccination coverage. Smaller offices and video reminders in waiting rooms were associated with enhanced 2-dose compliance among children younger than 9 years. A greater understanding of interoffice variability in influenza vaccine delivery by US pediatric providers should allow for the creation of more effective strategies to improve pediatric influenza vaccination rates.

A postmarketing evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in adults 18-49 years of age.

BACKGROUND: The Ann Arbor strain-live attenuated influenza vaccine (LAIV) was licensed in 2003 for use in the United States for individuals aged 5-49 years of age. As part of a postmarketing commitment to safety, LAIV was studied in adults 18-49 years participating in the Kaiser Permanente Health Plan over 5 influenza seasons. METHODS: Individuals received LAIV as part of routine care from October 2003 through March 2008. Using Kaiser Permanente databases, rates of medically attended events (MAEs) and serious adverse events (SAEs) in LAIV recipients were compared with rates in multiple non-randomized control groups which included a self-control group, matched unvaccinated controls, and matched controls vaccinated with inactivated influenza vaccine (TIV). RESULTS: A total of 21,340, 18,316, and 21,340 subjects received LAIV, TIV and no vaccine, respectively. More than 5500 MAE incidence rate comparisons were performed, and of these, 257 (5%) yielded statistically significant differences with 72 and 185 occurring at a higher and lower rate after LAIV compared with control groups, respectively. The pattern of MAE rate differences did not suggest any safety signal associated with LAIV. There were 47 SAEs noted, and no individual SAE occurred at a significantly higher or lower rate in LAIV recipients relative to control groups in any comparison. Only 2 SAEs (migraine/sinusitis and Bell's palsy) were considered possibly or probably related to LAIV. CONCLUSION: The results of this post-licensure evaluation of LAIV safety in individuals 18-49 years of age are consistent with pre- and post-approval clinical studies as well as reports to the U.S. Vaccine Adverse Events Reporting System, all of which demonstrated no significant adverse outcomes among eligible individuals following receipt of LAIV.

Quadrivalent Ann Arbor strain live-attenuated influenza vaccine.

Influenza B is responsible for significant morbidity in children and adults worldwide. For more than 25 years, two antigenically distinct lineages of influenza B viruses, B/Yamagata and B/Victoria, have cocirculated globally. Current influenza vaccine formulations are trivalent and contain two influenza subtype A strains (A/H1N1 and A/H3N2) but only one B strain. In a half of recent influenza seasons, the predominant circulating influenza B lineage was different from that contained in trivalent influenza vaccines. A quadrivalent live-attenuated influenza vaccine (Q/LAIV) that contains two B strains, one from each lineage, has been developed to help provide broad protection against influenza B. Q/LAIV was recently approved for use in the USA in eligible individuals 2-49 years of age. This review summarizes clinical trial data in support of Q/LAIV.

A postmarketing evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 5 through 17 years of age.

BACKGROUND: Live attenuated influenza vaccine (LAIV) was licensed in 2003 in the United States for use in individuals aged 5-49 years. METHODS: A prospective observational postmarketing study was conducted to evaluate the safety of LAIV. Rates of medically attended events (MAEs) and serious adverse events (SAEs) in eligible children aged 5-17 years receiving LAIV as part of routine care from October 2003 to March 2008 were compared with rates in nonrandomized self, matched unvaccinated, and matched trivalent inactivated influenza vaccine (TIV)-vaccinated controls. All MAEs and SAEs through 42 days postvaccination and all hospitalizations and deaths through 6 months postvaccination were analyzed. Statistical significance was assigned without multiplicity adjustment. RESULTS: 43,702 LAIV recipients were matched with similar numbers of TIV-vaccinated and unvaccinated children. Of approximately 9500 MAE incidence rate comparisons, 204 were statistically significantly higher and 168 were statistically significantly lower in LAIV recipients versus controls. No pattern of MAE rate differences suggested a safety signal with LAIV. Asthma/wheezing MAEs were not statistically increased in LAIV recipients. No anaphylaxis events occurred within 3 days postvaccination. Rates of SAEs were similar between LAIV and control groups. Two SAEs were considered possibly related to LAIV: Bell's palsy and nonspecific paroxysmal spell. CONCLUSIONS: Results of this postlicensure evaluation of LAIV safety in US children aged 5-17 years are consistent with preapproval clinical studies and Vaccine Adverse Event Reporting System reports, both of which demonstrated no significant increase in asthma/wheezing events or other adverse outcomes among eligible children who received LAIV.

The efficacy of live attenuated influenza vaccine against influenza-associated acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a frequent complication of influenza in young children. Influenza vaccination is known to protect against AOM by preventing influenza illness. We sought to determine the efficacy of the live attenuated influenza vaccine (LAIV) against influenza-associated AOM compared with placebo and trivalent inactivated influenza vaccine (TIV). LAIV is approved for eligible children aged ≥ 2 years in the United States and in several other countries. METHODS: AOM incidence data from 6 randomized, double-blind, placebo-controlled trials and 2 randomized, double-blind, TIV-controlled trials in children 6 to 83 months of age were pooled and analyzed. RESULTS: A total of 290 cases of AOM were identified in 24,046 study subjects. LAIV efficacy against influenza-associated AOM was 85.0% (95% confidence interval [CI], 78.3%-89.8%) compared with placebo and 54.0% (95% CI, 27.0%-71.7%) compared with TIV. Efficacy trended higher in those ≥ 24 months of age compared with those aged 6 to 23 months. In placebo-controlled trials, among children who acquired influenza despite vaccination, AOM was diagnosed in 10.3% of LAIV recipients and 16.8% of placebo recipients, representing a 38.2% (95% CI, 11.0%-58.2%) relative reduction in the development of AOM. In TIV-controlled studies, among subjects with breakthrough influenza illness, the proportions of LAIV and TIV recipients who developed AOM were similar. CONCLUSIONS: Children receiving LAIV had a high level of protection against influenza-associated AOM when compared with placebo or TIV. This was most evident in children older than 2 years, for whom LAIV is indicated. LAIV recipients who contracted breakthrough influenza illness despite vaccination developed AOM at a significantly lower rate than did unvaccinated children who developed influenza.

A postmarketing evaluation of the frequency of use and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years.

The 2007 US approval for use of live attenuated influenza vaccine (LAIV) in children aged 24-59 months included precautions against use in (1) children <24 months and children aged 24-59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. A postmarketing commitment was initiated to monitor LAIV use and the frequency of select safety outcomes in these cohorts. Vaccination rates and the frequency of hospitalizations or emergency department visits within 42 days after LAIV and trivalent inactivated influenza vaccine (TIV) administration were estimated from 2007 to 2009 claims data from a health insurance database. Rates of LAIV use per 10,000 child-days among cohorts 1, 2, and 4 were low relative to rates among the LAIV-recommended population (2007-2008; 0.03-0.78 vs. 1.32, 2008-2009; 0.08-3.26 vs. 5.94). However, rates of LAIV use per 10,000 child-days in cohort 3 were similar to rates among the LAIV-recommended population (2007-2008; 1.55 vs. 1.32, 2008-2009; 5.01 vs. 5.94). The rate of emergency department visits/hospitalizations within 42 days of vaccination with LAIV was the same as or less than the rate within 42 days of vaccination with TIV. Less restricted LAIV use in children with past wheezing may be related to the broad definition of recurrent wheezing used in national guidelines and the current study. In the small number of nonrecommended children receiving LAIV, no safety signals were identified.

Timing of the availability and administration of influenza vaccine through the vaccines for children program.

BACKGROUND: influenza vaccine must be distributed and administered each year during a limited time interval. To our knowledge, no previous studies have simultaneously evaluated the delivery and administration of privately purchased vaccines and influenza vaccines acquired through the Vaccines for Children (VFC) program. METHODS: a prospective, observational study was conducted in US outpatient pediatric offices, tracking all influenza vaccinations during the season by age group, first or second vaccination, the child's need for 1 or 2 doses, type of vaccine, and VFC status. RESULTS: a total of 42 and 84 practices completed the study in 2007 to 2008 and 2008 to 2009, respectively. In both seasons, initial shipments of VFC influenza vaccine generally arrived 4 to 5 weeks later than non-VFC shipments; VFC vaccine administration also started 1 month later than administration of privately purchased vaccine. Vaccine administration peaked in early November and late October in years 1 and 2, respectively, and declined rapidly thereafter. Overall, approximately one-half of all children who required 2 doses of vaccine were estimated to have received 2 doses. In both years, 2-dose compliance rates in the VFC population were 17% to 19% lower than those in the non-VFC population, possibly resulting from the VFC population's shorter time interval for second dose receipt. CONCLUSIONS: the VFC program is critical to ensuring financially vulnerable children have access to vaccination. Manufacturers, distributors, and public health officials should deliver VFC influenza vaccine to providers as quickly as possible. Pediatric healthcare providers should increase efforts to vaccinate all populations, especially the VFC population, in later months.

Trends in U.S. pediatric influenza vaccination from 2006 to 2010 among children with private insurance.

In the United States, recommendations for the annual influenza vaccination of children have expanded significantly in recent years. Additionally, to facilitate influenza vaccination delivery by providers, recent recommendations have encouraged vaccination as soon as vaccine is available and throughout the influenza season. However, until now, there have been limited data published describing pediatric providers' responses to these recent recommendations. De-identified, patient-level data from an electronic health care reimbursement claims database that contains more than 60% of all medical claims from outpatient settings in the US were analyzed. Only claims from privately insured children were available; administration of federally purchased vaccine (i.e., via the Vaccines for Children program) and vaccinations administered in settings where claims data are not generated were not captured. Weekly counts of influenza vaccinations administered to children 6 months through 18 years of age between August 1 and March 31 for the 2006-2007 through 2009-2010 seasons were projected to yield national estimates. Seasonal vaccination peaked in November for the 2006-2007 and 2007-2008 seasons, October for the 2008-2009 season, and September for the 2009-2010 season. The proportion of vaccinations administered before November 1 increased each season from 2006-2007 through 2009-2010. In all seasons, vaccination dramatically declined in December and continued at a steadily declining rate through the end of the season. Vaccine delivery to children 6-23 months of age was more dispersed over the vaccination season relative to older age groups. Among children 6-23 months and 2-18 years of age, use of preservative-free inactivated vaccine and live attenuated vaccine, respectively, increased significantly over the study period. While pediatric influenza vaccination occurred earlier each year, vaccination in later months has not increased in recent seasons, despite efforts to extend the vaccination season.