Picornavirus, the most common respiratory virus causing infection among patients of all ages hospitalized with acute respiratory illness.

We evaluated the prevalence of respiratory virus infection (RVI) in 403 illnesses of 364 persons hospitalized over a 2-year period with acute respiratory conditions using virus-specific reverse transcription-PCR (RT-PCR) assays in addition to cell culture and serology. RVIs were identified in >75% of children under 5 years of age and 25 to 37% of adults. The molecular assays doubled the number of infections identified; picornaviruses were the most frequent in patients of all ages, followed by respiratory syncytial virus and influenza viruses.

Direct and indirect effectiveness of influenza vaccination delivered to children at school preceding an epidemic caused by 3 new influenza virus variants.

BACKGROUND: Influenza is an uncontrolled epidemic disease that is vaccine preventable. New recommendations for universal immunization present a challenge to the implementation of vaccine delivery. This field trial examines the effectiveness of school-based clinics for vaccine delivery before an epidemic caused by 3 new influenza virus variants not contained in the vaccine. METHODS: Live attenuated influenza vaccine (LAIV) was offered to eligible children in elementary schools of eastern Bell County, Texas. Age-specific rates of medically attended acute respiratory illness for health plan members at the intervention site were compared with those for members at comparison sites during the epidemic, defined by viral surveillance at all sites. RESULTS: Almost 48% of children in elementary schools were vaccinated. Significant herd protection attributed to LAIV was detected for all age groups except 12-17-year-old students, who were not offered free vaccine. Approximately 2500 medical encounters were prevented at the intervention site. Inactivated vaccine provided marginal protection against the epidemic viruses. CONCLUSIONS: LAIV delivered to elementary-school children before an epidemic caused by 3 new variant influenza viruses generated significant cross-protection for the recipients and indirect (herd) protection for the community.

Improving influenza immunization in pregnant women and healthcare workers.

OBJECTIVE: To evaluate the effect of several strategies to increase influenza immunization in a multispecialty clinic. STUDY DESIGN: Retrospective electronic database analysis of influenza vaccinations in a 6-year period at Kelsey-Seybold Clinic in Houston, Texas. METHODS: We evaluated immunization rates in pregnant women and healthcare workers during 6 influenza seasons (2003-2004 to 2008-2009) after implementing the following strategies for pregnant women: assessing baseline immunization rates for obstetric providers, followed by direct encouragement and behavior modeling; implementing standing orders for influenza vaccination in pregnancy; and offering vaccination training to obstetricians and nurses. Further strategies implemented for healthcare workers included the following: conducting an employee survey about influenza knowledge, providing employee education based on survey findings and Centers for Disease Control and Prevention recommendations, making employee vaccines readily available and free of charge, designating immunization nurses to serve as clinical champions, monitoring and reporting the employee influenza vaccination rate, and recognizing the clinic with the highest employee vaccination rate. RESULTS: Influenza vaccination coverage rates in pregnant women increased from 2.5% at baseline to 37.4% in 2008-2009. Employee influenza vaccination coverage rates increased from 36.0% in 2003-2004 to 64.0% in 2008-2009. CONCLUSION: Low influenza vaccination rates in pregnant women and healthcare workers can be substantially improved using methods shown to be effective in other clinical settings.

Universal influenza vaccination and live attenuated influenza vaccination of children.

Influenza is an uncontrolled epidemic disease that is vaccine preventable. Each winter the peak of medically attended acute respiratory illness coincides with the peak of influenza virus activity. The anatomy of an urban influenza epidemic is presented highlighting the role of children in the spread of influenza. The efficacy and safety of the live attenuated influenza vaccine (LAIV) for children are documented and the indirect effectiveness (herd protection) of vaccinating schoolchildren is demonstrated. Children have the highest attack rates during influenza epidemics and the consequences of influenza virus infection can be severe regardless of the virus type--A(H1N1), A(H3N2), or B. Early in the epidemic, over one-half of the culture-positive illnesses will occur in school-aged children demonstrating their role in spreading the virus in the community. LAIV has been shown to be superior to inactivated vaccine for children and is safe even for children with mild intermittent asthma. One dose of LAIV is effective and gives almost immediate protection. LAIV administered by nasal spray is readily accepted by children. Several studies have demonstrated herd protection by immunizing schoolchildren. These studies have shown that immunizing schoolchildren is more efficient than vaccinating elderly and high-risk patients directly. Current recommendations for influenza vaccine give priority to more than 200 million persons in the United States, but vaccine coverage has not improved since 1997. Systematic delivery of influenza vaccine in school-based and workplace-based clinics would greatly enhance the control of epidemic influenza and help prepare for the next pandemic.

Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children with intermittent wheezing in an open-label field trial.

BACKGROUND: Safety of the intranasal, trivalent, live attenuated influenza vaccine (LAIV) in children with asthma is unknown. A previous report showed an "asthma signal" in children aged 18-35 months. METHODS: Healthy children aged 1.5-18 years with history of intermittent wheezing received single annual LAIV doses during a 4-year trial. Rates of medically-attended acute respiratory illnesses, including acute asthma exacerbation, during 0-14 and 0-42 days post-LAIV were compared with respective reference periods (before day 0 and after 14 or 42 days). To assess the risk of new-onset asthma, LAIV recipients without history of wheezing were analyzed. RESULTS: During each of the 4 years, 454, 656, 656, and 430 children, respectively, with intermittent wheezing who received LAIV had no increased risk for medically-attended acute respiratory illnesses, including asthma exacerbation. First-dose LAIV recipients, including those aged 1.5-4 years, and those receiving 2-4 consecutive annual doses had no increased risk. Children with parents' report of intermittent wheezing and those with administrative database codes for asthma during 2 prior years had no increased risk. During the 4 years, 2952, 3092, 2953, and 2478 children without history of wheezing had no increased risk of new-onset asthma. CONCLUSIONS: LAIV administration in children aged 1.5-18 years with history of intermittent wheezing was safe, and was not associated with increased risk for medically-attended acute respiratory illnesses, including acute asthma exacerbation. This was true for the first and 2-4 consecutive annual doses. Parents' report of intermittent wheezing was reliable. First-dose LAIV was not associated with new-onset asthma in children without history of wheezing.

Trivalent live attenuated intranasal influenza vaccine administered during the 2003-2004 influenza type A (H3N2) outbreak provided immediate, direct, and indirect protection in children.

OBJECTIVE: Live attenuated influenza vaccine may protect against wild-type influenza illness shortly after vaccine administration by innate immunity. The 2003-2004 influenza A (H3N2) outbreak arrived early, and the circulating strain was antigenically distinct from the vaccine strain. The objective of this study was to determine the effectiveness of influenza vaccines for healthy school-aged children when administered during the influenza outbreak. DESIGN/METHODS: An open-labeled, nonrandomized, community-based influenza vaccine trial was conducted in children 5 to 18 years old. Age-eligible healthy children received trivalent live attenuated influenza vaccine. Trivalent inactivated influenza vaccine was given to children with underlying health conditions. Influenza-positive illness was compared between vaccinated and nonvaccinated children. Medically attended acute respiratory illness and pneumonia and influenza rates for Scott and White Health Plan vaccinees were compared with age-eligible Scott and White Health Plan nonparticipants in the intervention communities. Herd protection was assessed by comparing age-specific medically attended acute respiratory illness rates in Scott and White Health Plan members in the intervention and comparison communities. RESULTS: We administered 1 dose of trivalent live attenuated influenza vaccine or trivalent inactivated influenza vaccine to 6569 and 1040 children, respectively (31.5% vaccination coverage), from October 10 to December 30, 2003. The influenza outbreak occurred from October 12 to December 20, 2003. Significant protection against influenza-positive illness (37.3%) and pneumonia and influenza events (50%) was detected in children who received trivalent live attenuated influenza vaccine but not trivalent inactivated influenza vaccine. Trivalent live attenuated influenza vaccine recipients had similar protection against influenza-positive illness within 14 days compared with >14 days (10 of 25 vs 9 of 30) after vaccination. Indirect effectiveness against medically attended acute respiratory illness was detected in children 5 to 11 and adults 35 to 44 years of age. CONCLUSION: One dose of trivalent live attenuated influenza vaccine was efficacious in children even when administered during an influenza outbreak and when the dominant circulating influenza virus was antigenically distinct from the vaccine strain. We hypothesize that trivalent live attenuated influenza vaccine provides protection against influenza by both innate and adaptive immune mechanisms.

Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian), a drift variant, during 2003-2004.

In the 2003-2004 influenza season, the predominant circulating influenza A (H3N2) virus in the United States was similar antigenically to A/Fujian/411/2002 (H3N2), a drift variant of A/Panama/2007/99 (H3N2), the vaccine strain. That year, a field study of trivalent live-attenuated influenza vaccine (LAIV-T) was conducted in Temple-Belton, Texas, as part of a larger community-based, non-randomized, open-label study in three communities that began in August 1998 [Gaglani MJ, Piedra PA, Herschler GB, Griffith ME, Kozinetz CA, Riggs MW, et al. Direct effectiveness of the trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against the 2000-2001 influenza A (H1N1) and B epidemic in healthy children. Arch Pediatr Adolesc Med 2004;158:65-73; Piedra PA, Gaglani MJ, Kozinetz CA, Herschler G, Riggs M, Griffith M, et al. Herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (CAIV-T) in children. Vaccine 2005;23:1540-8; Piedra PA, Gaglani MJ, Riggs M, Herschler G, Fewlass C, Watts M, et al. Live attenuated influenza vaccine, trivalent, is safe in healthy children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a community-based, nonrandomized, open-label trial. Pediatrics 2005;116:397-407]. Participants were healthy children aged 5-18 years. The analysis here concerns 6403 children in the Scott & White Health Plan (SWHP) database living within zip codes of the Temple-Belton area, of whom 1706 received LAIV-T and 548 received trivalent inactivated vaccine (TIV) in 2003, 983 had been previously vaccinated in 1998-2001, but not in 2002-2003 or 2003, and 3166 had never been vaccinated. The main outcome measure was medically-attended acute respiratory illness (MAARI). Surveillance culture results were incorporated into the analysis to estimate efficacy against culture-confirmed influenza illness. Vaccine effectiveness of LAIV-T against MAARI was 26% (95% confidence interval (CI) 11, 39). Vaccine efficacy of LAIV-T against culture-confirmed influenza illness including surveillance cultures of children in the SWHP database in the validation calculation was 56% (95% CI 24, 84). LAIV-T was cross-protective with a drift variant strain in 2003-2004, evidence that such vaccines could be important for preparing for a pandemic and for annual influenza.

Medically attended pediatric influenza during the resurgence of the Victoria lineage of influenza B virus.

OBJECTIVES: During the 2002-2003 season, a new variant of influenza B co-circulated with influenza A viruses. This study examines the characteristics and outcomes of children with influenza A and B virus infection vs. other acute respiratory illnesses. METHODS: A retrospective chart review was performed on children with laboratory-confirmed influenza infection, and influenza negative acute respiratory illnesses that prompted a hospital visit. RESULTS: Children with influenza were more often previously healthy and presenting with upper respiratory symptoms, while influenza negative patients typically had underlying medical conditions, and lower respiratory tract disease. Children with influenza B were older, were more likely to be in school, and presented with myositis more frequently than those with influenza A. A third of children with influenza A, and 42% with influenza B required hospitalization. The highest hospitalization rates were in infants under one year. No healthy children, and only 15% of those with chronic medical problems, had received influenza vaccine. Vaccine efficacy was estimated to be 82.6%. CONCLUSIONS: Most children with influenza were previously healthy. Overall, a third of children with influenza required hospitalization. Influenza A and B were clinically indistinguishable, except for older age and higher incidence of myositis in patients with influenza B. Influenza vaccine coverage in both healthy and high-risk children was low.

Asthma, influenza, and vaccination.

Exacerbations of asthma in children are usually triggered by virus infections. Many different respiratory viruses are associated with these exacerbations, but influenza viruses are frequently associated with those requiring hospitalization and are the only ones for which specific treatment and prophylaxis are available. Current studies have shown that influenza vaccines are safe for patients with asthma. The efficacy of inactivated influenza vaccines in preventing exacerbations of asthma has been questioned. The live attenuated influenza vaccine has been licensed recently in the United States, and studies have shown it to be safe and protective. A direct comparison of the inactivated and live attenuated influenza vaccines in children with asthma demonstrated superior protection by the latter. Live attenuated influenza vaccine, given by nasal spray, is better accepted by children for annual vaccination and is easier to administer. Universal vaccination of all children in school-based clinics will facilitate control of epidemic influenza and provide an infrastructure for control of future influenza pandemics.

Herd protection against influenza.

Mortality and hospitalization rates due to influenza have risen despite increasing vaccine coverage for the most vulnerable population; however, those most vulnerable to complications and death are the least likely to respond to the vaccine. New strategies for influenza control are needed and indirect effectiveness (herd protection) has been demonstrated for several currently used vaccines - rubella, H. influenzae type b, pneumococcus varicella and hepatitis A. The Japanese schoolchildren program provided proof of concept of indirect effectiveness of influenza vaccine. The Central Texas field trial has demonstrated significant herd protection of adults utilizing the live, attenuated influenza vaccine (LAIV) to children. Immunization of <20% of children at the intervention site resulted in an 8-18% reduction of medically attended acute respiratory illness in adults compared to rates in the comparison sites. LAIV given by nasal spray is efficacious against matched and poorly matched prevalent strains, easy to administer and readily accepted by children for annual immunization. School-based clinics could provide a platform for rapid deployment of vaccine accessible to all segments of the population. This strategy could be critical for control of pandemic influenza.

A response to strategy #2: streamlining the regulatory process.

Regulatory burden has contributed to the decline in the production of vaccines in the United States. Production of influenza virus vaccine is perilously limited at a critical period when vulnerable populations are increasing and the threat of a pandemic is looming. Regulatory bodies must work with manufacturers to facilitate implementation of new production practices, to ensure steady expansion of the supply of safe and effective vaccines.