Assessing optimal target populations for influenza vaccination programmes: an evidence synthesis and modelling study.

BACKGROUND: Influenza vaccine policies that maximise health benefit through efficient use of limited resources are needed. Generally, influenza vaccination programmes have targeted individuals 65 y and over and those at risk, according to World Health Organization recommendations. We developed methods to synthesise the multiplicity of surveillance datasets in order to evaluate how changing target populations in the seasonal vaccination programme would affect infection rate and mortality. METHODS AND FINDINGS: Using a contemporary evidence-synthesis approach, we use virological, clinical, epidemiological, and behavioural data to develop an age- and risk-stratified transmission model that reproduces the strain-specific behaviour of influenza over 14 seasons in England and Wales, having accounted for the vaccination uptake over this period. We estimate the reduction in infections and deaths achieved by the historical programme compared with no vaccination, and the reduction had different policies been in place over the period. We find that the current programme has averted 0.39 (95% credible interval 0.34-0.45) infections per dose of vaccine and 1.74 (1.16-3.02) deaths per 1,000 doses. Targeting transmitters by extending the current programme to 5-16-y-old children would increase the efficiency of the total programme, resulting in an overall reduction of 0.70 (0.52-0.81) infections per dose and 1.95 (1.28-3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk (50-64-y-olds) would prevent only 0.43 (0.35-0.52) infections per dose and 1.77 (1.15-3.14) deaths per 1,000 doses. CONCLUSIONS: This study proposes a framework to integrate influenza surveillance data into transmission models. Application to data from England and Wales confirms the role of children as key infection spreaders. The most efficient use of vaccine to reduce overall influenza morbidity and mortality is thus to target children in addition to older adults. Please see later in the article for the Editors' Summary

Characteristics of Fatal Cases of Pandemic Influenza A (H1N1) from September 2009 to January 2010 in Saurashtra Region, India

Background: India reported first case of 2009 pandemic influenza A (H1N1) virus infection in May, 2009 and Saurashtra region in August, 2009. We describe the characteristics of fatal cases of 2009 influenza A (H1N1) infection reported in Saurashtra region. Methods: From September, 2009 to January, 2010, we observed 71 fatal cases that were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals in Rajkot city. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection; the clinico-epidemiological features were observed and documented. Results: Median age of the deceased (71) was 29 years, and 57.7% were females. Median time observed was 5 days from onset of illness to diagnosis of influenza A (H1N1), and 57.7% were referred from general practitioner (OR=0.42, CI=0.24-0.74). Median hospital stay reported was 3 days. All admitted patients received oseltamivir, but only 16.9% received it within 2 days of onset of illness. The most common symptoms were cough (97.2%), fever (93%), sore throat and shortness of breath. Co-morbid conditions were present in almost half of the patients who ultimately died, the most common of which was pregnancy (OR=0.15, CI=0.04-0.52). Radiological pneumonia was reported in 98% patients. Conclusion: Residing in urban area, delayed referral from general practitioner, presence of co-existing condition, especially pregnancy was responsible for mortality among influenza A (H1N1) infected positive

Viral pathogens and acute lung injury: investigations inspired by the SARS epidemic and the 2009 H1N1 influenza pandemic.

Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage

Epidemiological and virological characteristics of pandemic influenza A (H1N1) 2009 in school outbreaks in China

Background: During the 2009 pandemic influenza H1N1 (2009) virus (pH1N1) outbreak, school students were at an increased risk of infection by the pH1N1 virus. However, the estimation of the attack rate showed significant variability. Methods: Two school outbreaks were investigated in this study. A questionnaire was designed to collect information by interview. Throat samples were collected from all the subjects in this study 6 times and sero samples 3 times to confirm the infection and to determine viral shedding. Data analysis was performed using the software STATA 9.0. Findings: The attack rate of the pH1N1 outbreak was 58.3% for the primary school, and 52.9% for the middle school. The asymptomatic infection rates of the two schools were 35.8% and 37.6% respectively. Peak virus shedding occurred on the day of ARI symptoms onset, followed by a steady decrease over subsequent days (p = 0.026). No difference was found either in viral shedding or HI titer between the symptomatic and the asymptomatic infectious groups. Conclusions: School children were found to be at a high risk of infection by the novel virus. This may be because of a heightened risk of transmission owing to increased mixing at boarding school, or a lack of immunity owing to socioeconomic status. We conclude that asymptomatically infectious cases may play an important role in transmission of the pH1N1 virus

Assessment of human influenza pandemic scenarios in Europe

The response to the emergence of the 2009 influenza A(H1N1) pandemic was the result of a decade of pandemic planning, largely centred on the threat of an avian influenza A(H5N1) pandemic. Based on a literature review, this study aims to define a set of new pandemic scenarios that could be used in case of a future influenza pandemic. A total of 338 documents were identified using a searching strategy based on seven combinations of keywords. Eighty-three of these documents provided useful information on the 13 virus-related and health-system-related parameters initially considered for describing scenarios. Among these, four parameters were finally selected (clinical attack rate, case fatality rate, hospital admission rate, and intensive care admission rate) and four different levels of severity for each of them were set. The definition of six most likely scenarios results from the combination of four different levels of severity of the four final parameters (256 possible scenarios). Although it has some limitations, this approach allows for more flexible scenarios and hence it is far from the classic scenarios structure used for pandemic plans until 2009

Genetic and clinical assessment of 2009 pandemic influenza in southern China

Introduction: South China has a proven role in the global epidemiology of previous influenza outbreaks due to its dual seasonal pattern. We present the virologic, genetic and clinical characterization of pandemic H1N1 influenza infection (pH1N1) in Shantou and Nanchang, cities in southern China, during the second wave of the 2009-2010 pandemic. Methodology: Nasopharyngeal swabs were collected from 165 individuals with influenza-like illness (ILI) who presented to the hospitals in Shantou and Nanchang. Laboratory diagnosis and characterization was performed by real-time PCR, virus isolation in embryonated chicken eggs, and sequencing. Results: pH1N1 activity was sustained in three different temporal patterns throughout the study period. The overall positivity rate of pH1N1 was 50% with major distribution among young adults between the ages of 13 and 30 years. High fever, cough, expectoration, chest pain, myalgia, nasal discharge and efficient viral replication were observed as major clinical markers whereas a substantial number of afebrile cases (17%) was also observed. Rate of hospitalization and disease severity (39%) and recovery (100%) were also high within the region. Furthermore, severe complications were likely to develop in young adults upon pH1N1 infection. Genetic characterization of the HA and NA genes of pH1N1 strains exhibited homogenous spread of pH1N1 strains with 99% identity with prototypic strains; however, minor unique mutations were also observed in the HA gene. Conclusion: The study illustrates the detailed characteristics of 2009 influenza pandemic in southern parts of China that might help to strategize preparedness for future pandemics and subsequent influenza seasons.</br

Respiratory syncytial virus: Clinical and epidemiological pattern in pediatric patients admitted to a children’s hospital between 2000 and 2013

INTRODUCTION: Respiratory syncytial virus (RSV) is the major causative organism associated with acute lower respiratory tract infections in children.The objective of this study was to describe the clinical and epidemiological pattern of RSV and identify risk factors for RSV infection. POPULATION AND METHODS: Prospective, cohort study on patients hospitalized due to acute lower respiratory tract infection at Hospital de Niños Ricardo Gutiérrez between March and November throughout the 2000-2013 period. The virological diagnosis of RSV, adenovirus, influenza and parainfluenza was performed by indirect immunofluorescence using nasopharyngeal aspirates. RESULTS: A total of 12,555 children were included, 38.2% (4798) had virus rescued from samples. RSV accounted for 81.8% of cases (3924/4798) with no significant annual variations (71.2- 88.1) and with an epidemic seasonal pattern(May through July); RSV was followed by influenza (7.6%), parainfluenza (5.9%), and adenovirus (4.7%).The median age of patients with RSV rescue (3924) was 7 months old (0- 214 months old), while 74.2% were younger than 1 year old, 43.1% were younger than 6 months old, 56.5% were males and the most common clinical presentation was bronchiolitis (60.7%). Comorbidities were observed in 41.6% of cases. The most common comorbidities were chronic respiratory disease (74%), congenital heart disease (14%), and chronic neurological disease (10.2%).Complications occurred in 25%of cases. The case fatality rate was 1.9% (74/3888). Independent predictors of RSV infection were age <3 months old (OR: 2.8 [2.14-3.67], p < 0.01),clinical presentation of bronchiolitis (OR: 1.54 [1.32-1.79], p < 0.01), and hypoxemia at the time of admission (OR: 1.84 [1.42-2.37], p < 0.01). CONCLUSIONS: RSV infection displayed a seasonal pattern and was associated with infants younger than 3 months old with bronchiolitis and hypoxemia at the time of admission.Fil: Lucion, María Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Juárez, María del Valle. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Viegas, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castellano, Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Romanin, Viviana Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Grobaporto, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bakir, Julia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Mistchenko, Alicia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Laboratorio de Virología; ArgentinaFil: Gentile, Ángela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin