Serious Complications Of Influenza Research Articles

Association Between Influenza Vaccination During Pregnancy and Infant Influenza Vaccination.

To examine the association between influenza vaccination during pregnancy and infant influenza vaccination. We conducted a retrospective analysis of individuals aged 15-49 years who were continually privately insured from August 2017 to May 2019 and had singleton live births between September 2017 and February 2018 and their infants. Influenza vaccination coverage was assessed for pregnant people during the 2017-2018 influenza season and for their infants during the 2018-2019 season using the 2017-2019 MarketScan data. Multivariate log-binomial regressions were conducted to examine the association between influenza vaccination during pregnancy and infant influenza vaccination. Of the 34,919 pregnant people in this analysis, 14,168 (40.6%) received influenza vaccination during pregnancy. Of the infants born to people vaccinated during pregnancy, 90.0% received at least one dose of influenza vaccine during the 2018-2019 season and 75.5% received at least two doses. Of the infants born to those not vaccinated during pregnancy, 66.3% received at least one dose of influenza vaccine and 51.8% received at least two doses. At-least-one-dose coverage was 35.7% higher (adjusted risk ratio [aRR] 1.34, 95% CI 1.33-1.36) and at-least-two-dose coverage was 45.8% higher (aRR 1.43, 95% CI 1.41-1.46) for infants born to people who received influenza vaccination during pregnancy compared with infants born to people who did not. Our results show a positive and statistically significant relationship between influenza vaccination during pregnancy and infant influenza vaccination status in their first season eligible for vaccination. Interventions to increase influenza vaccination coverage among pregnant people may also increase infant influenza vaccination coverage, offering greater protection against serious complications of influenza in both vulnerable populations.

Epidemiology and Clinical Outcomes of Patients with Confirmed Influenza in Mashhad, Iran in 2019

Background: Influenza is a contagious and acute viral disease caused by influenza viruses involving upper and lower respiratory tract system, especially in the cold seasons. Children aged less than 5 years old, elderly people, immunocompromised patients, pregnant women, and people with certain health conditions are at a higher risk for the disease and severe complications. Objectives: Due to the serious complications of influenza in certain groups, it is important to know which group of people are more at risk and need prevention strategies. This study aimed to investigate the patients with confirmed influenza, identify the people who are at a higher risk for infection, and assess the clinical outcomes of disease among patients. Methods: In this cross-sectional and descriptive study, we studied the files of all patients with confirmed influenza referred to the health centers in Mashhad, Iran, during autumn and winter of 2019 when influenza virus was prevalent. The disease was confirmed by reverse transcription polymerase chain reaction (RT-PCR) method. We studied all registered data related to the flu, including gender, age, residency, history of vaccination, risk factors, complications, and clinical outcomes. Results: In this study, 2977 patients (3% outpatients vs. 97% hospitalized) with flu like syndrome were tested by RT-PCR for influenza. Out of 84 outpatients, only two cases were positive for influenza. Among hospitalized patients, 80 cases (51% male vs. 49% female; age range: 1 - 87 years) had a positive RT-PCR test, and influenza type A was seen in 95% of cases. Pneumonia was the most common complication. Death happened in 29 (35.36%) patients and three (33.33%) cases with risk factors. The highest number of influenza patients (31 [37.8%]) had been reported from district No. 3 of Mashhad municipality, which is a crowded place and near the holy shrine. Conclusions: The results showed a high prevalence of complication and death among hospitalized patients, especially among those who did not have a risk factor for influenza viruses. Comprehensive vaccination programs and promotion of knowledge about transmission routes are two important measures for disease prevention and lower death rates.

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults.

Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-(n = 17) or B-LCII (n = 9) at 10–20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection.

Abstract 15390: Outcomes in Patients Hospitalized With Influenza-related Myocarditis in the United States: A Nationwide Study

Introduction: Acute myocarditis is a serious complication of influenza. While current reports suggest that subclinical cardiac involvement may be transient, myocarditis has been implicated in up to a third of sudden deaths in patients with influenza. Methods: Patients hospitalized with influenza in the US between 2003 and 2017 were identified using the Nationwide Inpatients Sample. They were subsequently classified to specify those with and without a diagnosis of myocarditis and specific outcomes of interest were compared between these subgroups. Results: : Between 2003 and 2017, 1,187,615 patients were hospitalized with influenza in the US. Of these, 2,430 patients (0.2%) were diagnosed with myocarditis while 1,185,185 patients (99.8%) did not have myocarditis. Patient characteristics and outcomes are shown in the table below. Independent predictors of myocarditis were: age (adjusted odds ratio [aOR]:0.98; 95% CI:0.98-0.99), male sex (aOR:1.21 ; 95% CI:1.01-1.46), Elixhauser score ≥3 (aOR:1.34; 95% CI:1.07-1.7), coagulopathy (aOR:1.67; 95% CI:1.29-2.17), valvular disease (aOR:1.5; 95% CI:1.07-2.1), abnormal weight loss (aOR:1.7; 95% CI:1.23-2.35), and a diagnosis of the 2009 H1N1 influenza virus (aOR:4.79; 95% CI:1.51-15.24). Independent predictors of death in patients hospitalized with influenza myocarditis were: age (aOR:1.04; 95% CI:1.01-1.06), stroke (aOR:11.16; 95% CI:1.57-79.49), shock (aOR:61.1; 95% CI:11.88-314.3), renal failure (aOR:3.56; 95% CI:1.2 -10.55), coagulopathy (aOR:2.62; 95% CI:1.04-6.6), and electrolyte disorders (aOR:3.19; 95% CI:1.07-9.47). Conclusions: Patients with influenza who develop myocarditis are younger than those without myocarditis and have more interventions, longer LOS and worse outcomes including a four-fold higher risk of cardiac arrest and a two-fold higher mortality rate. The strongest independent predictor of developing myocarditis was having the 2009 H1N1 influenza virus infection.

Influenza Vaccination: Accelerating the Process for New Vaccine Development in Older Adults.

Increased susceptibility to the serious complications of influenza is common in older adults. It is often ascribed to weakening of the immune system with age, and 90% of influenza-related deaths occur in older adults despite widespread vaccination programs. Common chronic conditions not only contribute to the loss of immune protection after vaccination and increase the risk for serious outcomes of influenza, but also increase the long-term consequences following hospitalization. Interactions of T and B cell ageing, chronic elevation of inflammatory cytokines (sometimes dubbed "inflammaging"), and dysregulated acute cytokine production pose major challenges to the development of new and more effective vaccines. However, these age-related problems are modifiable, as we have shown, and provide a clear margin for improvement. This chapter describes how an exclusive focus on developing influenza vaccines to stimulate strain-specific antibody responses against the hemagglutinin surface glycoprotein of the influenza virus, to the exclusion of other potentially important mechanisms, is missing the mark in terms of preventing the serious complications of influenza in older adults. Novel approaches are needed to enhance antibody-mediated protection against infection and stimulate cell-mediated immune responses to clear influenza virus from the lungs. These strategies for improving vaccine effectiveness will address the public health need for "vaccine prevention of disability" to mitigate the global pressures of aging populations on health and social care systems.

Increasing influenza vaccination acceptance in the homeless: A quality improvement project.

The US homeless population is predisposed to serious complications of influenza with increased likelihood of hospitalization and death. This quality improvement project sought to increase influenza vaccination in the homeless population of a rural area in the Midwest and improve provider knowledge of risks and preventive care responsibilities.

714. Predictors of Influenza-Associated Hospitalization and Pneumonia in a Pediatric Population in Bangkok, Thailand

BackgroundInfluenza infection in children can be severe, resulting in complications such as pneumonia, but may be mitigated by early recognition and administration of antivirals. In this study, we identified risk factors for hospitalization and pneumonia in a pediatric population presenting with influenza-like illness (ILI) in Thailand.MethodsOur study included pediatric patients (age < 18 years) presenting with ILI to inpatient and outpatient departments at a public hospital in Bangkok, Thailand, from 2009 to 2016. ILI was defined as fever plus cough or sore-throat, and pneumonia was defined as either lung radiographic or pulmonary examination abnormalities. Demographic and clinical data, as well as nasal and throat swabs, were collected during a one-time interview with patients presenting with ILI. Influenza infections were confirmed via RT-PCR testing of respiratory specimens. Retrospective chart review was used to collect data on individuals with influenza admitted for inpatient care.Results5,968 children (33.6%) were enrolled with ILI, of whom 1,530 (25.6%) were confirmed to be influenza by RT-PCR, of which 25.5% were influenza A(H1N1)pdm09, 31.5% influenza A(H3N2), and 43.0% influenza B. 124 (8.1%) patients were admitted, and 41 of these children (33.1%) developed pneumonia. Predictors of hospitalization included younger age (4.1 yrs for inpatients vs. 5.6 yrs) and higher presenting temperature (38.6C for inpatient vs. 38.0C) (both P < 0.05). Among children hospitalized with influenza, influenza subtype was not associated with pneumonia risk. Co-detection of Klebsiella pneumoniae was associated with an increased risk of pneumonia (P < 0.05. Patients with pneumonia were younger (4.1 yrs with vs. 6.4 yrs, P = NS), had a longer interval from fever onset to presentation at the hospital, and required longer hospital stays. Risk of pneumonia was decreased in patients who received oseltamivir within 48 hours of fever onset (odds ratio 0.36, 95% confidence interval 0.16–0.91).ConclusionPost viral pneumonia is a potentially serious complication of influenza, requiring longer hospitalization stay and affecting more than one-third of hospitalized pediatric patients with influenza. The risk of pneumonia can be reduced with early presentation for clinical care and prompt administration of oseltamivir following fever onset.Disclosures All authors: No reported disclosures.

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage

Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear.The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection.Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection.HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose.This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in older adults may be due to a strong IL-10 response to influenza following vaccination, and persistent CMV infection.

Discriminant biomarkers of acute respiratory distress syndrome associated to H1N1 influenza identified by metabolomics HPLC-QTOF-MS/MS platform.

Acute respiratory distress syndrome (ARDS) is a serious complication of influenza A (H1N1) virus infection. Its pathogenesis is unknown and biomarkers are lacking. Untargeted metabolomics allows the analysis of the whole metabolome in a biological compartment, identifying patterns associated with specific conditions. We hypothesized that LC-MS could help identify discriminant metabolites able to define the metabolic alterations occurring in patients with influenza A (H1N1) virus infection that developed ARDS. Serum samples from patients diagnosed with 2009 influenza A (H1N1) virus infection with (n=25) or without (n=32) ARDS were obtained on the day of hospital admission and analyzed by LC-MS/MS. Metabolite identification was determined by MS/MS analysis and analysis of standards. The specificity of the patterns identified was confirmed in patients without 2009 influenza A(H1N1) virus pneumonia (15 without and 17 with ARDS). Twenty-three candidate biomarkers were found to be significantly different between the two groups, including lysophospholipids and sphingolipids related to inflammation; bile acids, tryptophan metabolites, and thyroxine, related to the metabolism of the gut microflora. Confirmation results demonstrated the specificity of major alterations occurring in ARDS patients with influenza A (H1N1) virus infection.

Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison

ABSTRACTCellular immunity is important for protection against the serious complications of influenza in older adults. As it is unclear if newer influenza vaccines elicit greater cellular responses than standard vaccines, we compared responses to 2 standard and 2 newer licensed trivalent inactivated vaccines (TIVs) in a randomized trial in older adults. Non-frail adults ≥ 65 y old were randomly assigned to receive standard subunit, MF59-adjuvanted subunit, standard split-virus or intradermal split-virus TIV. Peripheral blood mononuclear cells (PBMC) harvested pre- and 3-weeks post-vaccination were stimulated with live A/H3N2 virus. PBMC supernatants were tested for interleukin 10 (IL-10) and interferon gamma (IFN-γ), and lysates for granzyme B (GrB). Flow cytometry identified CD4+ and CD8+ T- cells expressing intracellular IL-2, IL-10, IFN-γ, GrB, or perforin. Differences following immunization were assessed for paired subject samples and among vaccines. 120 seniors participated, 29-31 per group, which were well matched demographically. Virus-stimulated PBMCs were GrB-rich before and after vaccination, with minimal increases evident. Immunization did not increase secretion of IFN-γ or IL-10. However, cytolytic effector T-cells (CD8+GrB+perforin+) increased significantly in percentage post-vaccination in all groups, to similar mean values across groups. CD4+GrB+perforin+ T-cells also increased significantly after each vaccine, to similar mean values among vaccines. Vaccination did not increase the low baseline percentages of CD4+ or CD8+ T-cells expressing IFN-γ, IL-2 or IL-10 . In conclusion, participants had pre-existing cellular immunity to H3N2 virus. All 4 vaccines boosted cellular responses to a similar but limited extent, particularly cytolytic effector CD8+ T-cells associated with clinical protection against influenza.

The determinants of influenza vaccination effectiveness in adults aged 65 years and older: a systematic review

Purpose: Influenza vaccination effectiveness is generally lower in adults aged 65 years and above compared with healthy adults below the age of 65. This is generally attributed to weaker immune response in the elder population as a result of immunosenescence. However, the reasons for this phenomenon are not well characterised. The aim of this systematic review is to identify and summarise documented determinants of seasonal vaccine effectiveness in older adults. Methods & Materials: A literature search was conducted on bibliographic databases PubMed and EMBASE to identify relevant articles that investigate the determinants of influenza vaccine effectiveness in older adults up to July 4, 2015. Studies were eligible if they investigated potential determinants of seasonal influenza vaccination effectiveness in reducing the risk of laboratory-confirmed influenza, influenza-related hospitalisation or complications, and death or excess mortality in adults aged above 65. Results: Out of 37 relevant studies that were identified through the search process, eight studies that assess potential determinants of influenza vaccine effectiveness in older adults were identified. Six of the selected studies investigated vaccine factors, one assessed host factors, and one described factors involving vaccination policies and strategies as potential determinants of vaccine effectiveness in adults above 65 years old. The determinants that were significantly associated with influenza include vaccine type and route of administration, time elapsed after vaccination, frailty, and pneumococcal vaccination. However, vaccine effectiveness was evaluated using varying endpoints in these studies as investigators are interested in different primary outcomes, including laboratory-confirmed or diagnosed influenza, influenza-related hospitalisation or complications, and death or excess mortality. Conclusion: Documented determinants of influenza vaccine effectiveness in older adults can be broadly categorized into vaccine factors, host factors, and vaccination policies and strategies. Nevertheless, published studies that assess the impact of these determinants are relatively scarce and have lower internal validity as they are observational in nature. There is a need for more well-designed observational studies to identify and investigate the determinants of vaccine effectiveness in elder individuals, as they are at a higher risk of developing serious complications of influenza. The identification of these determinants will facilitate efforts to improve influenza vaccination in elder individuals.

Quantitative metabolome profiling reveals the involvement of the kynurenine pathway in influenza-associated encephalopathy

Influenza-associated encephalopathy is a serious complication of influenza and is the most common form of acute encephalitis/encephalopathy in Japan. The number of reports from other countries is increasing, reflecting international recognition and concern. Identification of a specific biomarker could provide important clues about the pathophysiology of influenza-associated encephalopathy. During the 2009–2011 flu seasons, 34 pediatric patients hospitalized with influenza complications, including influenza-associated encephalopathy, were enrolled in the study. Serum samples were collected during the acute and convalescent phases of disease. Patients were classified into encephalopathy (n = 12) and non-encephalopathy (n = 22) groups. Serum metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. Quantified data were evaluated for comparative analysis. Subsequently, a total of 55 patients with or without encephalopathy were enrolled for absolute quantification of serum kynurenine and quinolinic acid. Based on m/z values and migration times, 136 metabolites were identified in serum samples. During the acute phase of disease, three metabolites (succinic acid, undecanoic acid, and kynurenine) were significantly higher, and two other metabolites (decanoic acid and cystine) were significantly lower, in the encephalopathy group compared to the non-encephalopathy group (p = 0.012, 0.022, 0.044, 0.038, 0.046, respectively). In a larger patient group, serum kynurenine and its downstream product in tryptophan metabolism, quinolinic acid, a known neurotoxin, were significantly higher in the encephalopathy than the non-encephalopathy without febrile seizure group. Comprehensive metabolite profiles revealed five metabolites as potential biomarkers for influenza-associated encephalopathy; the tryptophan–kynurenine metabolic process could be associated with its pathophysiology.

Cell-Mediated Immune Response to Influenza Using Ex Vivo Stimulation and Assays of Cytokine and Granzyme B Responses.

The antibody response to vaccination has been the industry and regulatory standard for evaluating influenza vaccine efficacy. Although antibodies are an important defense mechanism providing sterilizing immunity, in older adults, the cellular immune response is also needed for clinical protection against the serious complications of influenza. Thus, the demonstration of enhanced antibody responses as a strategy for advancing new influenza vaccines through the standard clinical development pipeline may fail to translate to enhanced protection in the older population. In peripheral blood mononuclear cells (PBMC) challenged with live influenza virus, an increase in the interferon-γ:interleukin-10 (IFN-γ:IL-10) ratio and the level of the cytolytic mediator, granzyme B (GrzB), correlates with protection against influenza in vaccinated older adults. This chapter provides detailed methods for measuring these cell-mediated immune responses, which have been validated according to the International Conference on Harmonisation (ICH) guidelines. These immune correlates could be combined with antibody responses to improve the prediction of enhanced protection in vaccine trials in the older population.

Influenza Vaccines

Officials and professional societies treat influenza as a major public health threat for which the annual vaccine offers a safe and effective solution. In this article, I challenge these basic assumptions. I show that there is no good evidence that vaccines reduce serious complications of influenza, the outcomes the policy is meant to address. Moreover, promotional messages conflate "influenza" (disease caused by influenza viruses) with "flu" (a syndrome with many causes, of which influenza viruses appear to be a minor contributor). This lack of precision causes physicians and potential vaccine recipients to have unrealistic assumptions about the vaccine's potential benefit, and impedes dissemination of the evidence on nonpharmaceutical interventions against respiratory diseases. In addition, there are potential vaccine-related harms, as unexpected and serious adverse effects of influenza vaccines have occurred. I argue that decisions surrounding influenza vaccines need to include a discussion of these risks and benefits.

National Surveillance of Influenza-Associated Encephalopathy in Japan over Six Years, before and during the 2009–2010 Influenza Pandemic

Influenza-associated encephalopathy (IAE) is a serious complication of influenza and is reported most frequently in Japan. This paper presents an assessment of the epidemiological characteristics of influenza A (H1N1) 2009-associated encephalopathy in comparison to seasonal IAE, based on Japanese national surveillance data of influenza-like illness (ILI) and IAE during flu seasons from 2004–2005 through 2009–2010. In each season before the pandemic, 34–55 IAE cases (mean 47.8; 95% confidence interval: 36.1–59.4) were reported, and these cases increased drastically to 331 during the 2009 pandemic (6.9-fold the previous seasons). Of the 331 IAE cases, 322 cases were reported as influenza A (H1N1) 2009-associated encephalopathy. The peaks of IAE were consistent with the peaks of the influenza epidemics and pandemics. A total of 570 cases of IAE (seasonal A, 170; seasonal B, 50; influenza A (H1N1) 2009, 322; unknown, 28) were reported over six seasons. The case fatality rate (CFR) ranged from 4.8 to 18.2% before the pandemic seasons and 3.6% in the 2009 pandemic season. The CFR of pandemic-IAE was 3.7%, which is lower than that of influenza A−/B-associated encephalopathy (12.9%, p<0.001; 14.0%, p = 0.002; respectively). The median age of IAE was 7 years during the pandemic, which is higher than that of influenza A−/B-associated encephalopathy (4, p<0.001; 4.5, p = 0.006; respectively). However, the number of pandemic-IAE cases per estimated ILI outpatients peaked in the 0–4-year age group and data both before and during the pandemic season showed a U-shape pattern. This suggests that the high incidence of influenza infection in the 0–4 year age group may lead to a high incidence of IAE in the same age group in a future influenza season. Further studies should include epidemiologic case definitions and clinical details of IAE to gain a more accurate understanding of the epidemiologic status of IAE.

Cochrane Review: Neuraminidase inhibitors for preventing and treating influenza in children (published trials only)

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Selection criteria: Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups. © 2012 The Cochrane Collaboration.

Neuraminidase inhibitors for preventing and treating influenza in children (published trials only).

During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Characteristics and Outcomes of Pandemic 2009/H1N1 Versus Seasonal Influenza in Children With Cancer

Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08-65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04-10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02-1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.

Parapneumonic Empyema Deaths during Past Century, Utah

Bacterial pneumonia with empyema is a serious complication of influenza and commonly resulted in death during the 1918 influenza pandemic. We hypothesize that deaths caused by parapneumonic empyema are increasing in Utah once again despite advances in critical care and the availability of antimicrobial drugs and new vaccines. In this study, we analyzed the historical relationship between deaths caused by empyema and influenza pandemics by using 100 years of data from Utah. Deaths caused by empyema have indeed increased from 2000-2004 when compared with the historic low death rates of 1950-1975. Vaccine strategies and antimicrobial drug stockpiling to control empyema will be important as we prepare for the next influenza pandemic.

The use of oseltamivir during an influenza B outbreak in a chronic care hospital

Background Residents of nursing homes and long‐term care facilities are at a higher risk of outbreaks of influenza and of serious complications of influenza than those in the community. In late July 2005, a 90‐bed chronic care psycho‐geriatric hospital in Sydney, Australia, reported cases of influenza‐like illness (ILI) occurring amongst its residents. Methods An investigation to confirm the outbreak, and its cause, was undertaken. Influenza vaccination levels amongst residents, and the effects of antiviral drugs used for prevention and treatment, were assessed. Oseltamivir was only given to the residents, in the form of both treatment and prophylaxis. Results A total of 22 out of 89 residents met the clinical case definition of ILI with onset on or after 27 July 2005. This represents an attack rate of 25%. Oseltamivir was commenced on day 9 of the outbreak. Influenza B was identified in six residents as the causative agent of the outbreak. No deaths or acute hospitalization were recorded for this outbreak and there were no further reported cases after the introduction of oseltamivir. Vaccine effectiveness was 75% and the strain of influenza B isolated was well matched to that year’s vaccine. Conclusions There are few data on the use of oseltamivir in influenza B outbreaks. Early antiviral intervention appeared to curtail this outbreak of influenza B in a chronic care facility. We found high vaccine effectiveness in this frail, institutionalized population, highlighting the importance of influenza vaccination for residents of chronic care facilities.