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Over the past decade, pandemics caused by pandemic H1N1 (pH1N1) influenza virus in 2009 and severe acute respiratory syndrome virus type 2 (SARS-CoV-2) in 2019 have emerged. Both are high-impact respiratory pathogens originating from animals. Their wide distribution in the human population subsequently results in an increased risk of human-to-animal transmission: reverse zoonosis. Although there have only been rare reports of reverse zoonosis events associated with the ongoing coronavirus disease 2019 (COVID-19) pandemic from SARS-CoV-2 so far, comparison with the pH1N1 influenza pandemic can provide a better understanding of the possible consequences of such events for public and animal health. The results of our review suggest that similar factors contribute to successful crossing of the host species barriers in both pandemics. Specific risk factors include sufficient interaction between infected humans and recipient animals, suitability of the animal host factors for productive virus infection, and suitability of the animal host population for viral persistence. Of particular concern is virus spread to susceptible animal species, in which group housing and contact network structure could potentially result in an alternative virus reservoir, from which reintroduction into humans can take place. Virus exposure in high-density populations could allow sustained transmission in susceptible animal species. Identification of the risk factors and serological surveillance in SARS-CoV-2-susceptible animal species that are group-housed should help reduce the threat from reverse zoonosis of COVID-19.

Objectives: The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method: Longitudinal observational retrospective study, with patients aged 0–18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results: Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. Conclusions: Other viruses can be implicated in SARI in children. The role of viral codetection has not yet been completely elucidated. Keywords: Pandemic H1N1 Influenza, Co-detection, Pediatric intensive care unit, Severe acute respiratory infection (SARI), Child

Background: Influenza A(H1N1) causes serious complications in immunocompromised patients. The efficacy of seasonal vaccination in these patients has been questioned. Aim: To describe two outbreaks of influenza A(H1N1) in immunocompromised patients. Methods: Two outbreaks of influenza A(H1N1) occurred in our institution: on the kidney transplant ward in 2014 including patients early after kidney or simultaneous pancreas-kidney transplantation, and on the oncology ward in 2016 including patients receiving chemotherapy for malignant tumours. Factors leading to these outbreaks and the clinical efficacy of seasonal influenza vaccination were analysed. Findings: Altogether 86 patients were exposed to influenza A(H1N1) during the outbreaks, among whom the seasonal influenza vaccination status was unknown in 10. Only three out of 38 vaccinated patients were infected with influenza A(H1N1), compared with 20 out of 38 unvaccinated patients (P = 0.02). The death of one out of 38 vaccinated patients was associated with influenza, compared with seven out of 38 unvaccinated patients (P = 0.06). Shared factors behind the two outbreaks included outdated facilities not designed for the treatment of immunosuppressed patients. Vaccination coverage among patients was low, between 40% and 70% despite vaccination being offered to all patients free of charge. Vaccination coverage of healthcare workers on the transplant ward was low (46%), but, despite high coverage on the oncology ward (92%), the outbreak occurred. Conclusion: Seasonal influenza vaccination was clinically effective with both a reduced risk of influenza infection and a trend towards reduced mortality in these immunocompromised patients. Several possible causes were identified behind these two outbreaks, requiring continuous awareness in healthcare professionals to prevent further outbreaks. (C) 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Design Children with HIV are especially susceptible to complications from influenza infection, and effective vaccines are central to reducing disease burden in this population. We undertook a prospective, observational study to investigate the safety and immunogenicity of the inactivated split-virion AS03-adjuvanted pandemic H1N1(2009) vaccine in children with HIV. Setting National referral centre for Paediatric HIV in Ireland. Sample Twenty four children with HIV were recruited consecutively and received two doses of the vaccine. The serological response was measured before each vaccine dose (Day 0 and Day 28) and 2 months after the booster dose. Antibody titres were measured using a haemagglutination inhibition (HAI) assay. Seroprotection was defined as a HAI titre ≥ 1:40; seroconversion was defined as a ≥ fourfold increase in antibody titre and a postvaccination titre ≥ 1:40. Main outcome measures The seroconversion rates after prime and booster doses were 75% and 71%, respectively. HIV virological suppression at the time of immunization was associated with a significantly increased seroconversion rate (P = 0·009), magnitude of serological response (P = 0·02) and presence of seroprotective HAI titres (P = 0·017) two months after the booster dose. No other factor was significantly associated with the seroconversion/seroprotection rate. No serious adverse effects were reported. Vaccination had no impact on HIV disease progression. The AS03-adjuvanted pandemic H1N1 vaccine appears to be safe and immunogenic among HIV-infected children. A robust serological response appears to be optimized by adherence to a HAART regimen delivering virological suppression.

Background The World Health Organization recommends early antiviral treatment for patients with severe influenza illness or those at increased risk for severe illness. Objectives The aim of this study was to determine the proportion of cases with laboratory-confirmed A(H1N1)pdm09 infection that have been treated with antivirals in Germany during the pandemic (H1N1) 2009 and to investigate factors associated with the use of antivirals. Methods We analyzed cases with laboratory-confirmed A(H1N1)pdm09 infection notified to national health authorities in Germany between week 29/2009 and week 17/2010 using multivariable logistic regression. Severity of disease was defined by pneumonia or death. Results and conclusions Of 160 804 cases with laboratory-confirmed A(H1N1)pdm09 infection, 22% were treated with antivirals. Cases with severe disease were more likely to be treated with antivirals than cases without severe disease (odds ratio = 1·66; 95% confidence interval: 1·46–1·89). In the group with at least one underlying medical condition, only children aged between 1 and 4 years had significant lower odds for receiving antiviral treatment compared with cases in the age group 15 to 49 years (odds ratio = 0·75; 95% confidence interval: 0·6–0·94). In conclusion, the implementation of international recommendations on use of antivirals differed according to the age of patients in Germany during the pandemic (H1N1) 2009. This indicates that the potential of antivirals to prevent severe influenza might not have been fully exhausted. The reasons leading to the observed differences in patient management need to be investigated.

Background In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness. Objectives To assess the contribution of HA-RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009–2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied. Patients and methods We retrospectively analyzed HA-RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program. Results By HA-RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n = 8/24, 33·3%) than in patients with mild disease (n = 2/34, 6%) or in outpatients (n = 0/44) (Fisher's exact test P

Background Asthma was the most common chronic condition among adults hospitalized for 2009 pandemic influenza A (H1N1) (pH1N1). Objectives We describe the epidemiology and factors for severe outcomes among adults with asthma who were hospitalized or died from pH1N1 in California. Methods We reviewed California Department of Public Health pH1N1 reports from April 23, 2009 through August 11, 2009. Reports were included if the patient had pH1N1 (or non-subtypeable influenza A) infection by polymerase chain reaction in an adult (age ≥ 18 years) with asthma who was hospitalized or died. Patients were classified as having intermittent or persistent asthma on the basis of regular medications. Risk factors associated with severe outcomes (i.e., intensive care unit admission or death) vs those with less severe outcomes were assessed by chi-square tests and logistic regression. Results Among 744 identified patients, 170 (23%) had asthma (61% intermittent, 39% persistent). 132 of 142 (93%) patients had other chronic medical conditions. Severe outcomes occurred in 54 of 162 (33%), more commonly among those with renal disease (64% versus 31%; P = 0.04) and chest radiograph infiltrates (54% versus 11%; P

Introduction Previous influenza pandemics had second and on occasion third waves in many countries that were at times more severe than the initial pandemic waves. Objective This study aims to determine the seroepidemiology of successive waves of H1N1pdm09 infections in Singapore and the overall risks of infection. Methods We performed a cohort study amongst 838 adults, with blood samples provided upon recruitment and at 5 points from 2009 to 2011 and tested by haemagglutination inhibition (HI) with A/California/7/2009 (H1N1pdm09). Surveys on key demographic and clinical information were conducted at regular intervals, and associations between seroconversion and these variables were investigated. Results After the initial wave from June to September 2009, second and third waves occurred from November 2009 to February 2010 and April to June 2010, respectively. Seroconversion was 13·5% during the first wave and decreased to 6·2% and 6·8% in subsequent waves. Across the three waves, the elderly and those with higher starting HI titres were at lower risk of seroconversion, while those with larger households were at greater risk. Those with higher starting HI titres were also less likely to have an acute respiratory infection. Conclusions The second and third waves in Singapore had lower serological attack rates than the first wave. The elderly and those with higher HI titres had lower risk, while those in larger households had higher risk of seroconversion.

Background The present report compares prognosis in hospitalized cases with the H1N1 pandemic virus in two seasons. Methods Two series of hospitalized patients with laboratory-confirmed H1N1 pandemic influenza have been compared: 813 in the season 2009–2010 and 707 in the season 2010–2011. A detailed history of variables preceding hospital admission and during hospitalization was obtained by interview and clinical charts. A combined endpoint of death admission to intensive care was used as outcome due to the low number of deaths. Logistic regression was applied in the analysis for adverse outcome. Results Patients of the second season had different characteristics than in the first one (older, more underlying conditions, more malfunctioning organs and more symptoms). Patients with H1N1 pandemic virus when hospitalized were more frequently directly admitted to ICU during the 2010–2011 season than in the previous season (RR = 2·10; 95% confidence intervals CI, 1·55–2·85), as a consequence of a higher presence of sepsis and respiratory distress. These patients also showed during hospitalization a higher risk of ICU admission or death (RR = 3·22, 95% CI, 2·15–4·83). After adjusting for the differences in risk factors of adverse outcome, patients in the second season showed a higher risk of ICU admission and/or in-hospital death odds ratio (OR = 3·77, 95% CI, 2·30–6·18). Conclusion Hospitalized patients with H1N1 pandemic influenza during the second season were more severely affected at hospital admission and showed a worse prognosis than in previous season, independently of the differences found at hospital admission.

Pandemic influenza A (PA-H1N1) is a new strain of influenza virus that was first identified in Mexico and United States during the early part of 2009. The PA-H1N1 virus originated from the swine influenza (H1) virus circulating in North American pigs.

Background Effectiveness of pandemic plans and community compliance was extensively researched following the H1N1 pandemic. This systematic review examined community response studies to determine whether behavioural responses to the pandemic were related to level of knowledge about the pandemic, perceived severity of the pandemic and level of concern about the pandemic. Methods Literature databases were searched from March 2009 to August 2011 and included cross-sectional or repeated population surveys undertaken during or following the H1N1 pandemic which reported on community response to the pandemic. Studies using population subgroups and other respiratory diseases were excluded, as were mathematical modelling and qualitative studies. Results Nineteen unique studies were included. Fourteen reported pandemic knowledge, 14 reported levels of concern and risk perception and 18 reported pandemic behaviours. Awareness of the pandemic was high, and knowledge was moderate. Levels of concern and risk were low moderate and precautionary behavioural actions lower than intentions. The most commonly reported factors influencing adopting recommended behaviours were increased risk perception and older age, increased pandemic knowledge and being female. Conclusions Important implications for future pandemic planning were identified. A remarkable lack of intercountry variability in responses existed; however, differences between populations within a single country suggest one-size-fits-all plans may be ineffective. Secondly, differences between reported precautionary intentions and preventive behaviours undertaken may be related to people's perceived risk of infection.

Background Seasonal influenza activity varies with geography and time of year. Objective To describe how pandemic influenza A(H1N1)2009 [A(H1N1)pdm09] activity varied during the 2009–2010 pandemic. Methods We analyzed influenza virological data compiled by the World Health Organization from June 2009–August 2010. We calculated weekly proportions of A(H1N1)pdm09-positive specimens out of all A(H1N1)pdm09-positive specimens detected during the study period for each country. We compared parameters of pandemic activity (e.g., peak A[H1N1]pdm09 weekly proportion [peak activity], number of weeks between the 5th and 95th percentiles of A(H1N1)pdm09 cumulative weekly proportion [duration of activity]) between countries in temperate and tropical–subtropical regions. We quantified the proportion of A(H1N1)pdm09 out of all influenza A specimens by country and correlated it with countries' central latitudes. Results We analyzed data from 80 countries (47 temperate, 33 tropical–subtropical). The median proportion of cases identified during the peak week was higher in temperate (0·12) than in tropical–subtropical (0·09) regions (P

Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans. DOI: http://dx.doi.org/10.7554/eLife.12217.001, eLife digest Influenza viruses, commonly called flu, infect millions of people and animals every year and occasionally causes pandemics in humans. The immune system can neutralise flu viruses by recognising the proteins on the virus surface, generically referred to as antigens. These antigens change as flu viruses evolve to escape detection by the immune system. These changes tend to be relatively small such that exposure to one flu virus generates immunity that is still effective against other related flu viruses. However, over time, the accumulation of these small changes can result in larger differences such that prior infections no longer provide protection against the new virus. Influenza A viruses infect a wide variety of birds and mammals. Viruses can also transmit from one species to another, which may result in the introduction of viruses with antigens that are new to the recipient species and which have the potential to cause substantial outbreaks. Pig flu viruses have long been considered to be a potential risk for human pandemic viruses and were the source of the 2009 pandemic H1N1 virus. Importantly, humans often transmit flu viruses to pigs. Understanding the dynamics and consequences of this two-way transmission is important for designing effective strategies to detect and respond to new strains of flu. Influenza A viruses of the H1 and H3 subtypes circulate widely in pigs. However, it was poorly understood how closely related swine and human viruses circulating in different regions were to one another and how much the antigens varied between the different viruses. Lewis, Russell et al. have now analysed the antigenic variation of hundreds of H1 and H3 viruses from pigs on multiple continents. The antigenic diversity of recent swine flu viruses resembles the diversity of H1 and H3 viruses observed in humans over the last 40 years. A key factor driving the diversity of the H1 and H3 viruses in pigs is the frequent introduction of human viruses to pigs. In contrast, only one flu virus from a bird had contributed to the observed antigenic diversity in pigs in a substantial way. Once in pigs, human-derived flu viruses continue to evolve their antigens. This results in a tremendous diversity of flu viruses that can be transmitted to other pigs and also to humans. These flu viruses could pose a serious risk to public health because they are no longer similar to the current human flu strains. These findings have important implications not only for developing flu vaccines for pigs but also for informing the development of more-effective surveillance and disease-control strategies to prevent the spread of new flu variants. DOI: http://dx.doi.org/10.7554/eLife.12217.002

Introduction: Pandemic H1N1 is respiratory disease that spreads through droplets and can be prevented by vaccination of high risk groups, hand hygiene and through targeted precautionary lifestyle measures. It is pertinent to gauge knowledge about various a spects of the disease amongst residents of Lahore so as to devise and improve health education strategy. Methodology: Cross sectional descriptive survey was conducted and 134 residents of Lahore were selected through convenient sampling and interviewed. Re sults: Study showed mean age of the respondents were 35 +/_ `9.7years, out of which 55(41.7%) were males and 79(58.3%) were females with education level at more than intermediate in 117(87.3%) respondents while rest were below it.128 (95.5%) has heard of s wine flu, while 67(50%) heard about it from TV, 44(32.8%) from social media. 114(85.1%) identified that it can spread through sneezing and coughing , touching contaminated objects 64.6(47.8%), by inhaling contaminated air 95(70.9%), .57(42.5%) correctly id entified cough as symptom of pandemic influenza, sneeze 20(14.9%), fever 43(32.1%), 91(67.9%) told that influenza is treatable while only 59(44%) knew that vaccine is available to prevent it. 101(75.4%) respondents said that it can be prevented using masks , 91(67.9%) said by maintaining hand hygiene and 85(63.4%) by isolating the patient. 97(72.4%) respondents said that they would see the doctor if they have symptoms of influenza. Conclusion: Consistency in health education strategies is required and its recommended that disease chapter may be included in curriculum

Please cite this paper as: Basurto‐Dávila et al. (2012) Household economic impact and attitudes toward school closures in two cities in Argentina during the 2009 influenza A (H1N1) pandemic. Influenza and Other Respiratory Viruses. DOI: 10.1111/irv.12054. Background School closures were widely implemented in Argentina during the 2009 H1N1 influenza virus pandemic. Objectives To assess the economic impact of school closures on households, their effectiveness in preventing children from engaging in social group activities, and parental attitudes toward them. Methods Three schools that closed for 2 weeks in response to the pandemic were identified in two socioeconomically distinct cities in Argentina. All households with children enrolled in these schools were surveyed. Direct and indirect costs attributable to closures were estimated from the household perspective. Other information collected included children activities during the closures and parental attitudes toward the intervention. Results Completed questionnaires were returned by 45% of surveyed households. Direct and indirect costs due to closures represented 11% of imputed monthly household income in the city with lower socioeconomic status, and 3% in the other city (P = 0·01). Non‐childcare expenses and loss of workdays were more common in the city with lower socioeconomic status. Childcare expenses were less common and were experienced by a similar percentage of households in both cities. About three‐quarters of respondents in both cities agreed with the closures. The main concern among those who disagreed with closures was their negative impact on education. Children in more than two‐thirds of affected households left their home at least once during the closures to spend time in public places. Conclusion School closures may more significantly impact low‐income households. Authorities should consider the range of economic impacts of school closures among families when planning their implementation.

Background The 2009 influenza A (H1N1) pandemic was mild by historical standards, but was more severe in isolated Canadian Indigenous communities. Oseltamivir was used aggressively for outbreak control in an isolated northern Ontario First Nations community. We used mathematical modeling to quantify the impact of antiviral therapy on the course of this outbreak. Methods We used both a Richards growth model and a compartmental model to evaluate the characteristics of the outbreak based on both respiratory visits and influenza-like illness counts. Estimates of best-fit model parameters, including basic reproductive number (R0) and antiviral efficacy, and simulations, were used to estimate the impact of antiviral drugs compared to social distancing interventions alone. Results Using both approaches, we found that a rapidly growing outbreak slowed markedly with aggressive antiviral therapy. Richards model turning points occurred within 24 hours of antiviral implementation. Compartmental models estimated antiviral efficacy at 70–95%. Plausible estimates of R from both modeling approaches ranged from 4·0 to 15·8, higher than published estimates for southern Canada; utilization of aggressive antiviral therapy in this community prevented 962–1757 cases of symptomatic influenza and as many as 114 medical evacuations in this community. Conclusion Although not advocated in other settings in Canada, aggressive antiviral therapy markedly reduced the impact of a pandemic-related influenza A (H1N1) outbreak in an isolated Canadian First Nations community in northern Ontario, Canada. The differential risk experienced by such communities makes tailored interventions that consider risk and lack of access to medical services, appropriate.

Background/Objectives Japan has the highest frequency of neuraminidase (NA) inhibitor use against influenza in the world. Therefore, Japan could be at high risk of the emergence and spread of NA inhibitor-resistant viruses. The aim of this study was to monitor the emergence of NA inhibitor-resistant viruses and the possibility of human-to-human transmission during four influenza seasons in Japan. Methods To monitor antiviral-resistant A(H1N1)pdm09 viruses, we examined viruses isolated in four seasons from the 2008–2009 season through the 2011–2012 season in Japan by allelic discrimination, NA gene sequencing, and NA inhibitor susceptibility. Results We found that 157 (1·3%) of 12 026 A(H1N1)pdm09 isolates possessed an H275Y substitution in the NA protein that confers about 400- and 140-fold decreased susceptibility to oseltamivir and peramivir, respectively, compared with 275H wild-type viruses. The detection rate of resistant viruses increased from 1·0% during the pandemic period to 2·0% during the post-pandemic period. The highest detection rate of the resistant viruses was found in patients who were 0–9 years old. Furthermore, among the cases with resistant viruses, the percentage of no known exposure to antiviral drugs increased from 16% during the pandemic period to 44% during the post-pandemic period, implying that suspected human-to-human transmission of the resistant viruses gradually increased in the post-pandemic period. Conclusions A(H1N1)pdm09 viruses resistant to oseltamivir and peramivir were sporadically detected in Japan, but they did not spread throughout the community. No viruses resistant to zanamivir and laninamivir were detected.

Background During April–July 2009, U.S. hospitalization rates for 2009 pandemic influenza A (H1N1) virus (H1N1pdm09) infection were estimated at 4·5/100 000 persons. We describe rates and risk factors for H1N1pdm09 infection among American Indians (AIs) in four isolated southwestern U.S. communities served by the Indian Health Service (IHS). Methods We reviewed clinical and demographic information from medical records of AIs hospitalized during May 1–July 21, 2009 with severe acute respiratory infection (SARI). Hospitalization rates were determined using denominator data provided by IHS. H1N1pdm09 infection was confirmed with polymerase chain reaction, rapid tests, or convalescent serology. Risk factors for more severe (SARI) versus milder [influenza-like illness (ILI)] illness were determined by comparing confirmed SARI patients with outpatients with ILI. Results Among 168 SARI-hospitalized patients, 52% had confirmed H1N1pdm09 infection and 93% had >1 high-risk condition for influenza complications. The H1N1pdm09 SARI hospitalization rate was 131/100 000 persons [95% confidence interval (CI), 102–160] and was highest among ages 0–4 years (353/100 000; 95% CI, 215–492). Among children, asthma (adjusted odds ratio [aOR] 3·2; 95% CI, 1·2–8·4) and age

Background Previous research has demonstrated the value of macroeconomic analysis of the impact of influenza pandemics. However, previous modelling applications focus on high-income countries and there is a lack of evidence concerning the potential impact of an influenza pandemic on lower- and middle-income countries. Objectives To estimate the macroeconomic impact of pandemic influenza in Thailand, South Africa and Uganda with particular reference to pandemic (H1N1) 2009. Methods A single-country whole-economy computable general equilibrium (CGE) model was set up for each of the three countries in question and used to estimate the economic impact of declines in labour attributable to morbidity, mortality and school closure. Results Overall GDP impacts were less than 1% of GDP for all countries and scenarios. Uganda's losses were proportionally larger than those of Thailand and South Africa. Labour-intensive sectors suffer the largest losses. Conclusions The economic cost of unavoidable absence in the event of an influenza pandemic could be proportionally larger for low-income countries. The cost of mild pandemics, such as pandemic (H1N1) 2009, appears to be small, but could increase for more severe pandemics and/or pandemics with greater behavioural change and avoidable absence.

Background Laboratory‐confirmed deaths grossly underestimate influenza mortality burden, so that reliable burden estimates are derived from indirect statistical studies, which are scarce in low‐ and middle‐income settings. Objectives Here, we used statistical excess mortality models to estimate the burden of seasonal and pandemic influenza in China. Methods We modeled data from a nationally representative population‐based death registration system, combined with influenza virological surveillance data, to estimate influenza‐associated excess mortality for the 2004–2005 through 2009–2010 seasons, by age and region. Results The A(H1N1) pandemic was associated with 11·4–12·1 excess respiratory and circulatory (R&C) deaths per 100 000 population in rural sites of northern and southern China during 2009–2010; these rates were 2·2–2·8 times higher than those of urban sites (P

Background During the wave 1 of the influenza A(H1N1)pdm09 virus, Norway appeared to be suffering from high mortality rates. However, by the end of the pandemic, it was widely reported that the number of deaths were much lower than previous years. Objectives The mortality burden from influenza is often assessed by two different approaches: counting influenza-certified deaths and estimating the mortality burden using models. The purpose of this study is to compare the number of reported deaths with results from two different models for estimating excess mortality during the pandemic in Norway. Additionally, mortality estimates for the pandemic season are compared with non-pandemic influenza seasons. Methods Numbers on reported influenza A(N1h1)pdm09 deaths are gived by the Cause of Death Registry at Statistics Norway and an ad hoc registry at the Norwegian Institute of Public Health. Overall and Pnemumonia and Influenza certified mortality is modeled using Poission regression, adjusting for levels of reported influenza-like illness and seasonal and year-to-year variation. Results and conclusions Modelling results suggest that the excess mortality in older age groups is considerably lower during the pandemic than non-pandemic seasons, but there are indications of an excess beyond what was reported during the pandemic. This highlights the benefits of both methods and the importance of explaining where these numbers come from.

Please cite this paper as: Li et al. (2012) Immunogenicity and safety of a 2009 pandemic influenza A (H1N1) monovalent vaccine in Chinese infants aged 6–35 months: a randomized, double‐blind, controlled phase I clinical trial. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12028. Objectives The goal of this double‐blind, randomized, controlled clinical trial was to assess the safety and immunogenicity of two different doses of a monovalent split‐virion 2009 pandemic influenza A/H1N1 vaccine without adjuvant in Chinese infants aged 6‐35 months. Design and setting Subjects were randomly assigned to receive either a 2009 pandemic (H1N1) vaccine containing 7.5 or 15 μg haemagglutinin (HA) or a seasonal influenza vaccine. 2 doses of the H1N1 vaccines or the seasonal influenza vaccine were given 21 days apart in younger infants aged 6‐23 months or older infants aged 24‐35 months. Sample Serum samples were collected immediately before the first injection and before and 21 days after the second injection. Main outcome measures Primary outcomes were haemagglutinin inhibition (HI) antibody responses 21 days following each vaccination. Safety was monitoring throughout the study. Results The first vaccination of 7.5 μg and 15 μg H1N1 vaccine induced seroprotective antibody titers (HI titers ≥ 1: 40) in 42.9‐57.4% of younger infants and 49.1‐61.0% older infants. Immune responses after completion of the two dose schedule were comparable in both age groups with seroprotective rates of 91‐98% in each vaccine and age group and GMTs of 173‐263. The H1N1 vaccine elicited similar rates of local and systemic adverse reactions as the seasonal influenza vaccine. Conclusions The 2009 pandemic influenza A /H1N1 vaccine were highly immunogenic in infants aged 6‐35 months, and displayed a safety and reactogenicity profile similar to the seasonal influenza vaccine. Trial registration ClinicalTrial.gov identifier: NCT01047202

Background Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior. Conclusions The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.

Summary We report four patients with novel observations during extracorporeal membrane oxygenation support (ECMO). ECMO was initiated because of severe ARDS due to the primary H1N1 pandemic influenza pneumonia. Two patients had excessive conjugated hyperbilirubinemia and two had unproportional depletion of the coagulation factor IX. Pathogenetic mechanisms and clinical relevance of the noticed phenomena are discussed.

Two young boys with Duchenne muscular dystrophy, who had contracted 2009 pandemic influenza A/H1N1 (pH1N1), had been treated with antibiotics and steroids without significant improvement. One of them showed severe scoliosis. After hospitalization chest CT scan revealed extensive pulmonary bilateral segmental atelectasis. Their clinical and radiological findings rapidly improved when a sequential respiratory physiotherapy protocol was adopted that consisted of the application of multiple sessions of high-frequency chest wall oscillations, each one followed by mechanically assisted coughing manoeuvres. The protocol was well tolerated, effective, easy to apply and special positioning was not required. Fifteen days after treatment initiation both patients clinically recovered. This treatment can be very helpful for neuromuscular patients, particularly when scoliosis prevents conventional respiratory physiotherapy. Resumo: Duas crianças do sexo masculino com distrofia muscular de Duchenne que contraíram o vírus da gripe pandémica A/H1N1(pH1N1) de 2009 foram tratados com antibióticos e esteróides sem melhoria significativa.Um deles revelou escoliose severa. Depois da hospitalização, um TAC ao peito revelou uma atelectasia pulmonar segmentar bilateral extensa. Os seus resultados clínicos e radiológicos melhoraram rapidamente quando foi adoptado um tratamento de fisioterapia respiratória sequencial, consistente na aplicação de múltiplas sessões de oscilações torácicas de alta frequência, cada uma seguida por exercícios de tosse mecanicamente assistidos. O tratamento foi bem tolerado, eficaz e fácil de aplicar, sendo que não foi necessário um posicionamento especial. Quinze dias depois do início do tratamento, ambos os pacientes se encontravam clinicamente recuperados. Este tratamento pode ser muito útil em pacientes com doenças neuromusculares, particularmente quando a escoliose impede a fisioterapia respiratória convencional. KEYWORDS: Duchenne muscular dystrophy, High frequency chest wall oscillation, Pandemic H1N1 influenza, Atelectasis, : PALAVRAS-CHAVE, Distrofia muscular de Duchenne, Oscilação torácica de alta frequência, Pandemia de gripe H1N1, Atelectasia