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.

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.

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.

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.

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.

Respiratory viral infections in patients with chronic, obstructive pulmonary disease.

OBJECTIVES: The purpose of the present study was to apply reverse transcription-PCR (RT-PCR) assays to clinical specimens collected from patients with acute respiratory illness and chronic obstructive pulmonary disease (COPD). METHODS: One hundred and ninety-four samples from two different study cohorts were analysed using RT-PCR assays for picornaviruses, coronaviruses 229E and OC43, influenza A and B viruses, respiratory syncytial virus, parainfluenza types 1-3 viruses, and human metapneumovirus and a PCR assay for adenoviruses. The results were added to results obtained previously using cell culture and serologic methods. RESULTS: RT-PCR assays identified an additional 35 respiratory virus-associated illnesses not identified previously by cell culture or serology (n=46). Picornaviruses and coronaviruses were the most common viral infections identified only by RT-PCR. Overall, 41.8% of the acute respiratory illnesses evaluated were associated with a respiratory virus infection, with picornaviruses, coronaviruses and influenza viruses being the most common infections recognized. No human metapneumovirus infections were identified by RT-PCR assay. CONCLUSIONS: Respiratory viral infections are commonly associated with acute respiratory illness in COPD patients, and the use of RT-PCR assays significantly increases the ability to diagnose these infections.

The changing epidemiology of respiratory syncytial virus and influenza: impetus for new control measures.

BACKGROUND: Influenza and respiratory syncytial virus (RSV) are the most important causes of medically attended acute respiratory illnesses. Medical encounters for acute respiratory illness peak each winter, coinciding with the peak of influenza activity. RSV is the most important cause of hospitalization of infants for acute lower respiratory illness. METHODS: Surveillance of influenza and RSV have been maintained in Houston since 1974. Hospitalization rates during that period were compared with national data. U.S. influenza mortality rates and population dynamics were reviewed. RESULTS: The number of deaths attributed to influenza in the United States have increased from approximately 15,000 per year for the period from 1972 through 1984 to >50,000 from 1990 to 1999. RSV hospitalization rates for infants have more than doubled during the same period. Influenza epidemics have tended to occur earlier in Texas, with epidemic disease evident in early November in 3 of the last 4 years. CONCLUSIONS: Population dynamics with increased population density and urbanization probably are responsible for worsening of epidemics of the major respiratory viruses. New approaches to control will be necessary to reduce impact of these infections. These include earlier availability of influenza vaccine each autumn and use of antivirals and new vaccines for RSV.

Cold-adapted, live attenuated influenza vaccine.

The recently licensed cold-adapted, live attenuated influenza vaccine (CAIV-T, FluMist, MedImmune Vaccines Inc.) has the potential to enhance control of epidemic influenza. The intranasal vaccine has proven safety and efficacy. Regulatory constraints and cost of CAIV-T have hampered the introduction of the vaccine in the first year. Unwarranted concern about possible transmission of the virus from vaccine recipients to immunocompromised patients limited use in healthcare personnel. The intense influenza A(H3N2) epidemic of 2003-2004 has underscored the necessity of supplementing current efforts to control influenza. Over 120 deaths have been documented in children - the majority of which have been previously healthy. Use of CAIV-T in children will not only decrease the risk of serious disease, but also dampen the spread of the virus in the community and reduce exposure of patients who are at high risk of complications and death.

Direct and total effectiveness of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine against the 2000-2001 influenza A(H1N1) and B epidemic in healthy children.

BACKGROUND: The efficacy of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine (CAIV-T) against influenza A(H3N2) and B infections in healthy persons is established, but its effectiveness against natural influenza A(H1N1) infection is unknown. OBJECTIVE: To assess the effectiveness of CAIV-T in healthy children during the 2000-2001 influenza A(H1N1) and B epidemic. DESIGN: Community-based, nonrandomized, open-label trial from August 1998 through April 2001. SETTING: Intervention and comparison communities in central Texas. PARTICIPANTS: Healthy children, aged 1.5 to 18 years, from the intervention communities received a single dose of CAIV-T at least 1 time or more in 1998, 1999, and/or 2000. MAIN OUTCOME MEASURES: The incidence of medically attended acute respiratory illnesses during the 2000-2001 influenza epidemic was compared in 3794 health plan CAIV-T recipients with age-eligible, health plan nonrecipients in the intervention communities for direct effectiveness (n = 9325), and with those in the 2 comparison communities for total effectiveness (n = 16,264). RESULTS: The 2281 CAIV-T recipients in 2000 had significant direct protection against medically attended acute respiratory illness of 18% to 20% during the biphasic influenza A(H1N1) and B epidemic, and 17% to 26% during influenza A(H1N1) predominance. The 931 recipients of CAIV-T in 1999 containing influenza A/Beijing/262/95(H1N1) and B/Beijing/184/93-like viruses had persistent heterovariant protection against the 2000-2001 influenza A/New Caledonia/20/99(H1N1) and B/Sichuan/379/99 variants. The 616 recipients of a single CAIV-T dose in 1999 only, including those younger than 5 years with no prior natural exposure to influenza A(H1N1) viruses, showed persistent protection. CONCLUSION: Healthy children who received CAIV-T in 2000 or 1999 were protected against new variants of influenza A(H1N1) and B in the 2000-2001 influenza epidemic.