David K. Shay

Influenza and the Rates of Hospitalization for Respiratory Disease among Infants and Young Children

BACKGROUND Young children may be at increased risk for serious complications from influenzavirus infection. However, in population-based studies it has been difficult to separate the effects of influenzavirus from those of respiratory syncytial virus. Respiratory syncytial virus often circulates with influenzaviruses and is the most frequent cause of hospitalization for lower respiratory tract infections in infants and young children. We studied the rates of hospitalization for acute respiratory-disease among infants and children during periods when the circulation of influenzaviruses predominated over the circulation of respiratory syncytial virus. METHODS For each season from October to May during the period from 1992 to 1997, we used local viral surveillance data to define periods in Washington State and northern California when the circulation of influenzaviruses predominated over that of respiratory syncytial virus. We calculated the rates of hospitalization for acute respiratory disease, excess rates attributable to influenzavirus, and incidence-rate ratios for all infants and children younger than 18 years of age who were enrolled in either the Kaiser Permanente Medical Care Program of Northern California or the Group Health Cooperative of Puget Sound. RESULTS The rates of hospitalization for acute respiratory disease among children who did not have conditions that put them at high risk for complications of influenza (e.g., asthma, cardiovascular diseases, or premature birth) and who were younger than two years of age were 231 per 100,000 person-months at Northern California Kaiser sites (from 1993 to 1997) and 193 per 100,000 person-months at Group Health Cooperative sites (from 1992 to 1997). These rates were approximately 12 times as high as the rates among children without high-risk conditions who were 5 to 17 years of age (19 per 100,000 person-months at Northern California Kaiser sites and 16 per 100,000 person-months at Group Health Cooperative sites) and approached the rates among children with chronic health conditions who were 5 to 17 years of age (386 per 100,000 person-months and 216 per 100,000 person-months, respectively). CONCLUSIONS Infants and young children without chronic or serious medical conditions are at increased risk for hospitalization during influenza seasons. Routine influenza vaccination should be considered in these children.

Bronchiolitis-Associated Mortality and Estimates of Respiratory Syncytial Virus—Associated Deaths among US Children, 1979–1997

A 1985 estimate that 4500 respiratory syncytial virus (RSV)-associated deaths occur annually among US children has not been updated using nationally representative data. Thus, 1979-1997 multiple cause-of-death records for children <5 years old listing bronchiolitis, pneumonia, or any respiratory tract disease were examined. Deaths among children associated with any respiratory disease declined from 4631 in 1979 to 2502 in 1997. During the 19-year study period, 1806 bronchiolitis-associated deaths occurred (annual mean, 95 deaths; range, 66-127 deaths). Of these deaths, 1435 (79%) occurred among infants <1 year old. Congenital heart disease, lung disease, or prematurity was listed in death records of 179 (9.9%), 99 (5.5%), and 76 (4.2%) children dying with bronchiolitis, respectively. By applying published proportions of children hospitalized for bronchiolitis or pneumonia who were RSV-infected to bronchiolitis and pneumonia deaths, it was estimated that < or =510 RSV-associated deaths occurred annually during the study period, fewer than previously estimated.

The burden of community-acquired pneumonia in seniors: results of a population-based study.

Abstract Background. Pneumonia is recognized as a leading cause of morbidity in seniors. However, the overall burden of this disease—and, in particular, the contribution of ambulatory cases to that burden—is not well defined. To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged ⩾65 years that included both hospitalizations and outpatient visits for pneumonia. Methods. The study population consisted of 46,237 seniors enrolled at Group Health Cooperative who were observed over a 3-year period. Pneumonia episodes presumptively identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned to medical encounters were validated by medical record review. Characteristics of participants were defined by administrative data sources. Results. The overall rate of community-acquired pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65–69 years to 52.3 cases per 1000 person-years among those aged ⩾85 years. In this population, 59.3% of all pneumonia episodes were treated on an outpatient basis. In multivariate analysis, risk factors for community-acquired pneumonia included age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus, congestive heart failure, and smoking. Conclusions. On the basis of these data, we estimate that roughly 915,900 cases of community-acquired pneumonia occur annually among seniors in the United States and that ∼1 of every 20 persons aged ⩾85 years will have a new episode of community-acquired pneumonia each year.

Hospitalizations Associated With Influenza and Respiratory Syncytial Virus in the United States, 1993–2008

BACKGROUND Age-specific comparisons of influenza and respiratory syncytial virus (RSV) hospitalization rates can inform prevention efforts, including vaccine development plans. Previous US studies have not estimated jointly the burden of these viruses using similar data sources and over many seasons. METHODS We estimated influenza and RSV hospitalizations in 5 age categories (<1, 1-4, 5-49, 50-64, and ≥65 years) with data for 13 states from 1993-1994 through 2007-2008. For each state and age group, we estimated the contribution of influenza and RSV to hospitalizations for respiratory and circulatory disease by using negative binomial regression models that incorporated weekly influenza and RSV surveillance data as covariates. RESULTS Mean rates of influenza and RSV hospitalizations were 63.5 (95% confidence interval [CI], 37.5-237) and 55.3 (95% CI, 44.4-107) per 100000 person-years, respectively. The highest hospitalization rates for influenza were among persons aged ≥65 years (309/100000; 95% CI, 186-1100) and those aged <1 year (151/100000; 95% CI, 151-660). For RSV, children aged <1 year had the highest hospitalization rate (2350/100000; 95% CI, 2220-2520) followed by those aged 1-4 years (178/100000; 95% CI, 155-230). Age-standardized annual rates per 100000 person-years varied substantially for influenza (33-100) but less for RSV (42-77). CONCLUSIONS Overall US hospitalization rates for influenza and RSV are similar; however, their age-specific burdens differ dramatically. Our estimates are consistent with those from previous studies focusing either on influenza or RSV. Our approach provides robust national comparisons of hospitalizations associated with these 2 viral respiratory pathogens by age group and over time.

Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection

OBJECTIVE. Pediatric influenza-associated death became a nationally notifiable condition in the United States during 2004. We describe influenza-associated pediatric mortality from 2004 to 2007, including an increase of Staphylococcus aureus coinfections. METHODS. Influenza-associated pediatric death is defined as a death of a child who is younger than 18 years and has laboratory-confirmed influenza. State and local health departments report to the Centers for Disease Control and Prevention demographic, clinical, and laboratory data on influenza-associated pediatric deaths. RESULTS. During the 2004–2007 influenza seasons, 166 influenza-associated pediatric deaths were reported (n = 47, 46, and 73, respectively). Median age of the children was 5 years. Children often progressed rapidly to death; 45% died within 72 hours of onset, including 43% who died at home or in an emergency department. Of 90 children who were recommended for influenza vaccination, only 5 (6%) were fully vaccinated. Reports of bacterial coinfection increased substantially from 2004–2005 to 2006–2007 (6%, 15%, and 34%, respectively). S aureus was isolated from a sterile site or endotracheal tube culture in 1 case in 2004–2005, 3 cases in 2005–2006, and 22 cases in 2006–2007; 64% were methicillin-resistant S aureus. Children with S aureus coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those who were not coinfected. CONCLUSIONS. Influenza-associated pediatric mortality is rare, but the proportion of S aureus coinfection identified increased fivefold over the past 3 seasons. Research is needed to identify risk factors for influenza coinfection with invasive bacteria and to determine the impact of influenza vaccination and antiviral agents in preventing pediatric mortality.

Epidemiology of Seasonal Influenza: Use of Surveillance Data and Statistical Models to Estimate the Burden of Disease

The US Centers for Disease Control and Prevention (CDC) uses a 7-component national surveillance system for influenza that includes virologic, influenza-like illness, hospitalization, and mortality data. In addition, some states and health organizations collect additional influenza surveillance data that complement the CDCs surveillance system. Current surveillance data from these programs, together with national hospitalization and mortality data, have been used in statistical models to estimate the annual burden of disease associated with influenza in the United States for many years. National influenza surveillance data also have been used in suitable models to estimate the possible impact of future pandemics. As part of the public health response to the 2003-2004 influenza season, which was noteworthy for its severe effect among children, new US surveillance activities were undertaken. Further improvements in national influenza surveillance systems will be needed to collect and analyze data in a timely manner during the next pandemic.

Estimates of US influenza-associated deaths made using four different methods.

Background  A wide range of methods have been used for estimating influenza‐associated deaths in temperate countries. Direct comparisons of estimates produced by using different models with US mortality data have not been published.

Mask use, hand hygiene, and seasonal influenza-like illness among young adults: A randomized intervention trial

BACKGROUND During the influenza A(H1N1) pandemic, antiviral prescribing was limited, vaccines were not available early, and the effectiveness of nonpharmaceutical interventions (NPIs) was uncertain. Our study examined whether use of face masks and hand hygiene reduced the incidence of influenza-like illness (ILI). METHODS A randomized intervention trial involving 1437 young adults living in university residence halls during the 2006-2007 influenza season was designed. Residence halls were randomly assigned to 1 of 3 groups-face mask use, face masks with hand hygiene, or control- for 6 weeks. Generalized models estimated rate ratios for clinically diagnosed or survey-reported ILI weekly and cumulatively. RESULTS We observed significant reductions in ILI during weeks 4-6 in the mask and hand hygiene group, compared with the control group, ranging from 35% (confidence interval [CI], 9%-53%) to 51% (CI, 13%-73%), after adjusting for vaccination and other covariates. Face mask use alone showed a similar reduction in ILI compared with the control group, but adjusted estimates were not statistically significant. Neither face mask use and hand hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI cumulatively. CONCLUSIONS These findings suggest that face masks and hand hygiene may reduce respiratory illnesses in shared living settings and mitigate the impact of the influenza A(H1N1) pandemic. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00490633.

Risk factors for bronchiolitis-associated deaths among infants in the United States

Background. Risk factors for bronchiolitis deaths have not been described on a national level. We examined the epidemiology of and identified risk factors for bronchiolitis-associated deaths among infants in the United States. Methods. Multiple cause-of-death and linked birth/infant death data for 1996 through 1998 were used to examine bronchiolitis-associated infant deaths. Risk factors were assessed by comparing infants who died with bronchiolitis and surviving infants. Results. During 1996 through 1998 there were 229 bronchiolitis infant deaths, resulting in an average annual infant mortality rate of 2.0 per 100 000 live births. The majority (55%) of infant deaths occurred among infants ages 1 through 3 months. The bronchiolitis mortality rate was highest among infants weighing <1500 g at birth (VLBW) as compared with infants weighing 1500 to 2499 g (LBW) and ≥2500 g at birth (29.8, 6.4 and 1.3 per 100 000 live births, respectively). Sixty-three percent of bronchiolitis deaths were among infants weighing ≥2500 g. VLBW and LBW infants remained at an increased risk of dying with bronchiolitis after controlling for other risk factors. Other risk factors included increasing birth order, low 5-min Apgar score, young maternal age, unmarried mother and tobacco use during pregnancy. Conclusions. VLBW and LBW infants are at increased risk of dying with bronchiolitis, even when taking into account other risk factors. Although infants weighing <2500 g at birth are at increased risk for dying with bronchiolitis, the majority of bronchiolitis deaths occur among infants of normal birth weight.

Immunogenicity and Reactogenicity of 1 versus 2 Doses of Trivalent Inactivated Influenza Vaccine in Vaccine-Naive 5–8-Year-Old Children

BACKGROUND Two doses of trivalent inactivated influenza vaccine (TIV) are recommended for children <9 years old receiving vaccine for the first time, but compliance is suboptimal. This study assessed the need for a second dose of TIV in this age group. METHODS In this prospective, open-label study, 232 influenza vaccine-naive 5-8-year-olds enrolled in a health maintenance organization received 2 doses of TIV in fall 2004. Serum for antibody titer measurement was obtained at 3 time points (n = 222). Parents completed diaries for 5 days. RESULTS Both doses of vaccine were well tolerated. The strongest predictor of a protective antibody response (> or =1 : 40) after 1 dose of TIV was baseline seropositive status. In multivariate analysis adjusting for age, sex, and baseline serostatus, the proportion of children with protective antibody responses was significantly higher after 2 doses than after 1 dose of TIV for each antigen (P < .001, for A/H1N1; P = .01, for A/H3N2; P < .001, for B). Age and sex were not independently predictive of a protective antibody response. Over one-third of children had antibody responses <1:40 for the type B vaccine component, even after 2 doses. CONCLUSIONS The present study supports the need for 2 doses of TIV in 5-8-year-olds receiving TIV for the first time. Efforts to increase compliance with the 2-dose recommendation are warranted.