The clinical predictors of and vaccine protection against severe influenza infection in children

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Abstract

Influenza infection in children causes a tremendous global burden. In this study, we aimed to investigate the clinical predictors of severe influenza among children. We retrospectively included hospitalized children who had laboratory‐confirmed influenza infection and were admitted to a medical center in Taiwan between 2010 and 2018. Severe influenza infection was defined as needing intensive care. We compared demographics, comorbidities, vaccine status and outcomes between patients with severe and nonsevere infection. There were 1030 children hospitalized for influenza infection: 162 patients needed intensive care and 868 patients did not. Multivariable analysis revealed that an age below 2 years (adjusted odds ratio [aOR] 3.31, 95% confidence interval [CI] 2.22–4.95), underlying cardiovascular disease (aOR 1.84, 95% CI 1.04–3.25), neuropsychological (aOR 4.09, 95% CI 2.59–6.45) or respiratory disease (aOR 3.87, 95% CI 1.42–10.60), patchy infiltrates (aOR 2.52, 95% CI 1.29–4.93), pleural effusion (aOR 6.56, 95% CI 1.66–25.91), and invasive bacterial coinfection (aOR 21.89, 95% CI 2.19–218.77) were significant clinical predictors of severe disease, whereas severe infection was less likely in individuals who had received influenza and pneumococcal conjugate vaccines (PCVs) (aOR 0.51, 95% CI 0.28–0.91; aOR 0.35, 95% CI 0.23–0.51, respectively). The most significant risk factors associated with severe influenza infection were an age under 2 years, comorbidities (cardiovascular, neuropsychological, and respiratory diseases), patchy infiltrates or effusion shown on chest X‐rays, and bacterial coinfections. The incidence rate of severe disease was significantly lower in those who had received influenza vaccines and PCVs.

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The frequency of influenza and bacterial coinfection: a systematic review and meta‐analysis

Eili Klein, Bradley Monteforte, Alisha Gupta … (2016)

Aim Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients. Method A systematic search of MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria. Results Twenty‐seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results (I 2 = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta‐regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%–56%) and 28% (95% CI, 16%–40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small‐study publications may have biased the results. Conclusions The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large‐scale studies are needed to better understand the etiology of influenza bacterial coinfection.

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Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study.

Fatimah S. Dawood, A. Iuliano, Carrie Reed … (2012)

18,500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. We estimate that globally there were 201,200 respiratory deaths (range 105,700-395,600) with an additional 83,300 cardiovascular deaths (46,000-179,900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. None. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Influenza and the rates of hospitalization for respiratory disease among infants and young children.

Hector Izurieta, William W Thompson, Piotr Kramarz … (2000)

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. 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. 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). 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.