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Purpose To estimate risk for narcolepsy in defined time windows following exposure to adjuvanted A(H1N1) pandemic vaccine (Pandemrix) and impact of different definitions of index date for the narcolepsy diagnosis. Methods Vaccine exposure in approximately 30% of the Swedish population in 2009 was linked to information on narcolepsy diagnosis retrieved from the national patient registry. Cases were verified by a systematic chart review. Poisson regression was used to compare incidence in defined time windows following vaccination. Results Of 266 cases of narcolepsy identified, 25% (66/266) were prevalent cases with symptom onset documented before vaccine exposure. Incident cases had a median time interval between first symptom and the date recorded in the patient registry of 64 weeks (IQR 39-107) when vaccinated (N = 182) and 65 weeks (IQR 51-72) when unvaccinated (N = 16). With first symptom defining index date, the adjusted risk for narcolepsy in younger patients was increased 14 times during the first year after vaccination, three times elevated the second year, but with no detectable increased risk more than 2 years after vaccination exposure. Using the index date from the patient registry, the adjusted increase in risk was about seven times elevated for all three time intervals. Conclusions The magnitude of the estimated increased risk for narcolepsy following exposure to the A(H1N1) pandemic vaccine is highly dependent on the method used to determine the index date for disease onset. The sometimes very long and potentially variable interval from first symptom to a health care registry diagnosis complicates estimations of risk.

Background: Since the 21st century, humans have experienced five public health emergencies: the severe acute respiratory syndrome (SARS), type A H1N1 influenza (H1N1), Middle East respiratory syndrome (MERS), Ebola virus disease (EVD), and the new coronavirus pneumonia (COVID-19). They caused a large number of casualties and a wider psychological crisis, which might cause severe consequences such as post-traumatic stress disorder and suicide. Aims: To reveal the law of formation of public psychological crisis in public health emergencies, and draw lessons from it. To provide ideas for effectively deal with these psychological crisis problems and fundamentally curbing the occurrence of public health emergencies. Method: Through the method of literature research, ‘public health incidents’, ‘psychological crisis’, ‘mental health’, ‘psychological intervention’, ‘SARS’, ‘H1N1’, ‘MERS’, ‘EVD’, and ‘COVID-19’ were used to search literatures in the databases such as PubMed, Springer, and Sciencedirect, and the literatures were summarized, sorted, and studied. Results: (1) The public health emergencies caused a universal psychological crisis. The main manifestations were depression, compulsion, despair, etc. The people involved mainly include patients, suspected isolated patients, medical staff, and the general public in the epidemic situation. (2) People’s psychological state often experienced stress stage, shock stage, acceptance, and reorganization. Only some susceptible individuals couldn’t complete effective psychological reconstruction, resulting in serious psychological disorders. Individual susceptibility is related to genetic factors, adversity, and traumatic stimuli experienced in early life. Conclusion: To reduce these psychological crisis problems, we should establish and improve the psychological crisis intervention or rescue system of public health emergencies, it was still necessary to live in harmony with nature, get rid of the inappropriate habit of preying on wild animals, in order to prevent the cross-species transmission of the virus between wild animals and humans, and to fundamentally avoid the occurrence of major infectious diseases.

After the influenza H1N1 pandemic of 2009, the seasonal A/Brisbane/59/2007 strain was replaced by the A/California/07/2009 strain for the influenza virus vaccine composition. After several seasons with no indications on the occurrence of antigenic drift, A/Michigan/45/2015 was chosen as the H1N1 vaccine strain for the 2017/2018 season. Since the immune response to influenza is shaped by the history of exposure to antigenically similar strains, the potential cross-protection between seasonal human influenza vaccine strains and the emerging pandemic strains was investigated. Human serum samples were tested by hemagglutination inhibition and single radial hemolysis assays against A/Brisbane/59/2007, A/California/07/2009, and A/Michigan/45/2015 strains. Strong cross-reactions between A/California/07/2009 and A/Michigan/45/2015 strains were observed in 2009/2010, most likely induced by the start of the 2009 pandemic, and the subsequent post-pandemic seasons from 2010/2011 onward when A/California/07/2009 became the predominant strain. In the 2014/2015 season, population immunity against A/California/07/2009 and A/Michigan/45/2015 strains increased again, associated with strong cross-reactions. Whereas hemagglutination inhibition assay has a higher sensitivity for detection of new seasonal drift, the single radial hemolysis assay is an excellent tool for determining the presence of pre-existing immunity, allowing a potential prediction on the booster potential of influenza vaccines against newly emerging drifted strains.

Influenza in pregnancy is a common condition that is associated with increased risk of hospital admission. Women with comorbidities are at greater risk of severe outcomes. There are substantial gaps in our knowledge of the impact of severe influenza on perinatal outcomes, especially in low and middle-income countries, but preterm birth, fetal death, infant respiratory infection and hospital admission may be increased. Thus, influenza is major burden on health services. Immunisation is cost-effective, safe and effective at preventing influenza in pregnant women and their infants but policies and uptake vary worldwide. Operational challenges and concern over the safety, efficacy and necessity of the immunisation are common and there is a lack of evidence on how to overcome these barriers. This review identifies learning points relevant to the current COVID-19 pandemic through describing the epidemiology and impact of seasonal and A(H1N1)pdm09 influenza in pregnancy, alongside the effectiveness and use of immunisation., Highlights • Influenza in pregnancy causes excess hospital admissions and preventable deaths of both mothers and babies. • Influenza vaccines are cost-effective, safe and effective at preventing influenza in pregnant women and their infants. • Policies on immunisation against influenza in pregnancy vary worldwide and many countries have poor uptake. • Operational challenges in delivering immunisation and concern over the safety, efficacy and necessity of the immunisation are common but there is insufficient evidence on how to overcome these barriers.

This study examined relations between risk perception/self-efficacy and handwashing intentions/behaviors during the A (H1N1) pandemic influenza. Data were collected from a longitudinal sample of Costa Ricans (NT1/T2 = 449/97). Results revealed that males and females presented a different social cognitive pattern in reaction to A (H1N1) pandemic. In females, the effects of risk perception/self-efficacy on handwashing behaviors were fully mediated by handwashing intentions. In males, self-efficacy influenced both directly and indirectly on handwashing behaviors, and risk perceptions showed no significant effect on handwashing behaviors. These results suggest that gender oriented protocols should be adopted by public health authorities in order to educate males and females in preventing both A (H1N1) and seasonal influenza.

Producción Científica, Background and methods Elderly people have experienced several influenza natural infections and seasonal vaccinations during their lives. The aim of this work was to evaluate in an elderly Spanish population the presence of antibodies (Abs) against some 1940s era A/H1N1 influenza viruses and some new influenza viruses. We also evaluated the homologous and heterotypic responses after seasonal influenza vaccination. We collected pre- and post-vaccination serum samples from 174 elderly people (≥65 years) who were vaccinated with seasonal influenza vaccines during the 2006–2007, 2008–2009, 2009–2010, and 2010–2011 northern hemisphere influenza campaigns. The presence of Abs against the 1940s era A/Weiss/43 and A/FM/1/47 strains of the A/H1N1 influenza virus was evaluated by using hemagglutination inhibition assays. Results Pre-vaccination Abs against the A/Weiss/43 and A/FM/1/47 strains were present at protective titres (≥1/40) in 43.7% and 20.1% of the study population respectively. Seasonal influenza vaccination induced heterotypic seroconversion against A/Weiss/43 in 16.1% of the individuals and against A/FM/1/47 in 13.2% of the individuals. The seroprotection rate for the study population after seasonal vaccination was 63.2% against A/Weiss/43 and 31.0% against A/FM/1/47. The heterotypic response did not satisfy the European Medicament Agency criteria for people aged ≥60 years. Conclusions A moderate percentage of elderly people had Abs against the 1940s era A/Weiss/43 and A/FM/1/47 strains of the A/H1N1 influenza subtype. Seasonal influenza vaccination induced a low but significant heterotypic response against both 1940s era influenza strains, reaching a high seroprotection rate for the A/Weiss/43 strain. Seasonal influenza vaccination can increase, within certain limitations, the Abs titres against old influenza strains not included in the composition of the vaccine itself.

A mathematical model for the transmission dynamics of the 2009 A/H1N1 influenza epidemic in the Republic of Korea is developed. The simulation period is separated into three consecutive periods based on the government's intervention strategies: the nonpharmaceutical strategy is used during Period 1. The nonpharmaceutical and antiviral strategies are executed during Period 2 and the vaccine strategy is added during Period 3. During Period 1, we estimate the reduction in the transmission rate due to the government's intervention policies as a difference between the data-fitted and uncontrolled transmission rate that is derived from the basic reproductive number, R0, of the model without intervention. This quantified reduced transmission rate is used as an upperbound of the nonpharmaceutical control for studying optimal control strategies, which is a new approach for determining the realistic upperbound of control. In this study, we also explore the real-time prediction of incidence using the mathematical model during the early stage of the epidemic. We investigate the impact of vaccination coverage and timing with respect to the cumulative incidence. The result implies that early vaccination plays a significant role for preventing the epidemic.

Knowledge of the severity of an influenza outbreak is crucial for informing and monitoring appropriate public health responses, both during and after an epidemic. However, case-fatality, case-intensive care admission and case-hospitalisation risks are difficult to measure directly. Bayesian evidence synthesis methods have previously been employed to combine fragmented, under-ascertained and biased surveillance data coherently and consistently, to estimate case-severity risks in the first two waves of the 2009 A/H1N1 influenza pandemic experienced in England. We present in detail the complex probabilistic model underlying this evidence synthesis, and extend the analysis to also estimate severity in the third wave of the pandemic strain during the 2010/2011 influenza season. We adapt the model to account for changes in the surveillance data available over the three waves. We consider two approaches: (a) a two-stage approach using posterior distributions from the model for the first two waves to inform priors for the third wave model; and (b) a one-stage approach modelling all three waves simultaneously. Both approaches result in the same key conclusions: (1) that the age-distribution of the case-severity risks is "u"-shaped, with children and older adults having the highest severity; (2) that the age-distribution of the infection attack rate changes over waves, school-age children being most affected in the first two waves and the attack rate in adults over 25 increasing from the second to third waves; and (3) that when averaged over all age groups, case-severity appears to increase over the three waves. The extent to which the final conclusion is driven by the change in age-distribution of those infected over time is subject to discussion., Published in at http://dx.doi.org/10.1214/14-AOAS775 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

Reports of histopathological findings in a patient infected with H1N1 influenza virus are limited in the literature, although many deaths have occurred because of this viral infection. In an otherwise healthy individual with no underlying co-morbid conditions, this virus passes off as a very mild disease. However, it can be fatal in the presence of underlying risk factors. Here, we present the autopsy findings of a patient who died of H1N1 infection, but who was apparently healthy with no predisposing ailments. The autopsy revealed chronic kidney disease and caseating granulomatous lymphadenitis in addition to the known classical diffuse alveolar damage picture seen in this condition. These underlying co-morbidities may provide greater insight and a better understanding of this infection.

Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact. Conclusion: Following the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps.

International audience; We conducted a multicentre test negative case control study to estimate the 2013–14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: −1.9;85.4), 39.4% (95%CI: −32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18–64, 65–79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: −145.3;65.4), 25.6% (95%CI: −36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18–64, 65–79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013–14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. © 2016 Taylor & Francis.

The adaptive evolution of influenza virus is an important question, but predicting its evolutionary future will be more challenging. Here, we investigated the mutation characteristic of influenza virus based on the complete genome data of 2009 (H1N1) influenza A virus. By assuming that evolution proceeds via the accumulation of mutations , we analyzed the mutation networks at four different time stages and found that the network structure follows the characteristics of a scale-free network. These results will be important for epidemiology and the future control of influenza viruses. Furthermore, we predicted the predominant mutation virus strain by using the early mutation network of influenza viruses, and this result was consistent with the WHO recommendation for the candidate vaccine of influenza virus. The key contribution of this study is that we explained the biological significance of this scale-free network for influenza pandemic and provided a potential method for predicting the candidate vaccine by using the early-stage network.

INTRODUCTION Following the initial outbreak of A/H1N1pdm09, periodic resurgences of the virus, with variable morbidity and mortality, have been reported from various parts of India including the temperate Kashmir region of northern India. An outbreak of A/H1N1 was reported in early 2015 across India with a high morbidity and mortality. We studied patients during the outbreak in Kashmir. METHODS Patients (n=1780, age 1 month to 90 years, median 35 years) presenting with acute respiratory illness to a tertiary care hospital in Srinagar, Kashmir from October 2014 to April 2015 were recruited. After clinical data recording, combined throat and nasal swabs were collected in viral transport medium and tested by real-time RT-PCR for influenza viruses. All influenza A positive samples were further subtyped using primers and probes for A/H1N1pdm09 and A/H3 whereas influenza B samples were further subtyped into B/Yamagata and B/Victoria lineages. Virus isolation, hemagglutination inhibition testing, sequencing and phylogenetic analysis was carried out using standard procedures. Testing for H275Y mutation was done to determine sensitivity to oseltamivir. All patients received symptomatic therapy and influenza positive patients were administered oseltamivir. RESULTS Of the 1780 patients, 540 (30%) required hospitalization and 533 tested positive for influenza [influenza A=517(A/H1N1pdm09=437, A/H3N2=78 with co-infection of both in 2 cases); influenza B=16 (B/Yamgata=15)]. About 14% (n=254) had been vaccinated against influenza, having received the NH 2014-15 vaccine, 27 (11.3%) of these testing positive for influenza. Sixteen patients, including 4 pregnant females, died due to multi-organ failure. HA sequencing depicted that 2015 isolates belonged to Clade 6B.1. No H275Y mutation was reported from A/H1N1 positives. CONCLUSION Resurgent outbreak of A/H1N1pdm09, with emergence of clade 6B.1, in 2014-15 resulted in high rate of hospitalizations, morbidity and mortality. Periodic resurgences and appearance of mutants emphasize continued surveillance so as to identify newer mutations with potential for outbreaks and severe outcomes.

The latest report of the United Kingdom Confidential Enquiry into Maternal Mortality, conducted by the MBRRACE-UK collaboration, was published in December 2014. The report has moved from triennial to annual publication with a chapter on each specific cause of maternal death included once every 3 years. In 2010–12, overall maternal mortality fell to 10.1 per 100,000 maternities; a 27% decrease compared to 2003–5. Whilst the maternal mortality rate from genital tract sepsis more than halved from its 20-year high in 2006–2008, sepsis per-se accounted for almost 25% of deaths. One in 11 of all deaths were associated with sepsis related to influenza, the majority 2009/A H1N1 influenza, which, in the presence of an effective vaccine, were largely preventable. The benefits of influenza vaccination should be promoted and women offered vaccination at any stage of pregnancy. Thrombosis was the leading cause of direct death, highlighting the ongoing importance of thromboprophylaxis.

In sub-Saharan Africa, little is known about the epidemiology of pandemic-prone influenza viruses in urban settings. Using data from a prospective sentinel surveillance network, we characterized the emergence, epidemiology, and transmission dynamics of 2009 pandemic A/H1N1 influenza (H1N1pdm09) in Kampala, Uganda. After virus introduction via international air travel from England in June 2009, we estimated the basic reproductive number in Kampala to be 1.06-1.13, corresponding to attack rates of 12-22%. We subsequently identified 613 cases of influenza in Kampala from 2009 to 2015, of which 191 (31.2%) were infected with H1N1pdm09. Patients infected with H1N1pdm09 were more likely to be older adult (ages 35-64) males with illness onset during rainy season months. Urban settings in sub-Saharan Africa are vulnerable to importation and intense transmission of pandemic-prone influenza viruses. Enhanced surveillance and influenza pandemic preparedness in these settings is needed.

Objective To evaluate the risk of adverse pregnancy outcomes following A/H1N1 vaccination in pregnant women. Methods This observational cohort study compared vaccinated and non-vaccinated pregnant women in EFEMERIS, a French prescription database including pregnant women. Women who ended their pregnancy in South Western France between October 21, 2009 and November 30, 2010 (the period of the French vaccination campaign) were included. Two non-vaccinated women were individually matched to each vaccinated woman by month and year of pregnancy onset. Conditional logistic regression and Cox proportional hazards regression were used to evaluate associations between each outcome (all-cause pregnancy loss, preterm delivery, small for gestational age (SGA) and neonatal pathology) and A/H1N1 vaccination during pregnancy. Results 1645 women of the 12,120 (13.6%) in the database who were administered A/H1N1 vaccine during pregnancy were compared to 3290 non-vaccinated women. Most were vaccinated in December 2009 (61%) with a non-adjuvanted vaccine (93%). The risks of pregnancy loss (adjusted HR = 0.56; 95% CI = 0.31–1.01), of preterm birth (adjusted HR = 0.82; 95% CI = 0.64–1.06), and of neonatal pathology (adjusted OR = 0.70; 95% CI = 0.49–1.02) did not differ between the vaccinated and the non-vaccinated groups. The rate of SGA was lower in the vaccinated group than in the non-vaccinated group (0.5% vs. 1.4%; adjusted OR = 0.36; 95% CI = 0.17–0.78). Conclusion There was no significant association between adverse pregnancy outcomes and vaccination with a non-adjuvanted A/H1N1 vaccine during pregnancy.

The main objective of this study was to evaluate the contribution of a newly implemented daily surveillance system to the management of the 2009 A(H1N1) influenza pandemic by the military decision-makers at different levels in the French Department of Defence.The study sample included all medical advisors in the Ministry of Defence and the French Armed Forces Staff and also the members of the specific committee dedicated to flu pandemic control. The variables studied were mental representation of epidemiology, relevance, usefulness, and real-time use of surveillance data using quantitative questionnaires and qualitative face-to-face semistructured interviews.Among the risk managers of the flu pandemic in the Armed Forces, 84% responded. The data generated by epidemiological surveillance were considered relevant and useful, and were reported as effectively used. On the basis of the information produced, concrete actions were planned and implemented in the French Armed Forces.In a pandemic situation involving low mortality, the daily monitoring of the disease did not target public health issues, but it was mainly used to assess the availability of the Armed Forces in real time. For the military staff, epidemiological surveillance represents an essential information tool for the conduct of operations.

Aims: In response to the 2009 outbreak of A/H1N1 influenza, Swedish authorities decided on a programme for universal vaccination. Over 60% of the population received at least one dose of vaccine. This study examines demographic factors and perceptions related to the decision whether or not to become vaccinated. Methods: A combined web/postal survey was conducted ( n = 1587, response rate 53%) in late spring 2010. Questions reported here concerned perceptions, precautionary behaviours and vaccination decision. Results: Main reasons for becoming vaccinated were concerns about spreading the disease to relatives or in the community and confidence in the good effect of vaccination. Vaccination rates were higher among women, those with young children or belonging to a risk group. Main reasons for abstaining were belief that the flu was not a serious threat, low risk of spreading the disease, concern about side-effects and perceived uncertainties in information. Three profiles representing different patterns of thought and beliefs were identified by cluster analysis, respectively labelled as a vulnerable, a trusting and a sceptical group. Vaccination rates and precautionary behaviours were demonstrated to differ between these groups. Conclusions: Perceptions relating to the 2009 pandemic are likely to influence uptake of vaccination in the future. Authorities need to be aware of different patterns of beliefs and attitudes among the public, and that these may vary in different phases. Communication of risk needs to be dynamic and prepared to engage with the public before, during and even for some time after the acute risk period.

Objective Describe acceptability of pandemic A(H1N1) influenza vaccination by Essential Community Workers (ECWs) from Alicante province (Spain) in January 2010. Evaluate the correlation with attitudes, beliefs, professional advice and information broadcasted by media. Method In this cross-sectional study, face-to-face interviews were conducted with 742 ECWs to assess their attitudes towards vaccination against the pandemic influenza strain. A multivariable regression model was made to adjust the Odds Ratios (ORs). Results Some ECWs reported having been vaccinated with seasonal vaccine, 21.5% (95%IC 18.6–24.9); only 15.4% (95%IC 12.8–18.4) with the pandemic one. ECWs vaccinated regularly against seasonal flu (OR 5.1; 95%IC 2.9–9.1), those who considered pandemic influenza as a severe or more serious disease than seasonal flu (OR 3.8; 95%IC 2.1–6.7) and those who never had doubts about vaccine safety (OR 3.7; 95%IC2.1–6.7) had a better acceptance of pandemic vaccine. Finally, 78.7% (95%IC 75.1–81.4) had doubts about pandemic vaccine's effectiveness. Conclusion The vast amount of information provided by the media did not seem to be decisive to prevent doubts or to improve the acceptability of the vaccine in ECWs. Professional advice should be the focus of interest in future influenza vaccination campaigns. These results should be taken into account by health authorities.

Introduction: We conducted a prospective, multi-centre, data collection survey of homeopathic practice in treatment of influenza-like illness in India during the 2009 pandemic of A/H1N1 influenza (‘swine flu’, SF). Aims: To survey the practice of homeopathic practitioners in India in the management of SF, with respect to: (a) patients' symptoms at presentation and at follow-up (FU) consultation; (b) homeopathic medicines prescribed. Methods: Data collection took place from October 2009 to February 2010, at the peak of the pandemic. All patients satisfying the minimum diagnostic symptoms of SF were eligible for inclusion. Data per appointment (in person or by telephone) were recorded by practitioners in spreadsheet format. All records were anonymised and included: whether patient was immunised against A/H1N1; influenza symptoms at consultation; the homeopathic medicine/s prescribed; whether antiviral medicine prescribed. Results: Twenty-three homeopathic physicians contributed to data collection. At the first appointment, 1126 patients had valid SF symptoms. A total of 89 different combinations of SF symptoms was observed, the most common being temperature >38°C + cough + runny nose (n = 170; 15.1%). A total of 44 different remedies (or combinations of remedies) were used at these first appointments, the most frequently prescribed being Arsenicum album (n = 265; 23.5%). For a total of 99 FU appointments with valid SF symptoms, Arsenicum album was prescribed most frequently overall (n = 28; 28.0%). Conclusions: In our sample, the 2009 A/H1N1 influenza pandemic in India was characterised by several prominent symptoms and symptom/medicine associations, particularly temperature >38°C + cough + runny nose, associated with Arsenicum album. Future studies should collect additional keynote prescribing symptoms that influence the choice of homeopathic medicine.

Background. Oseltamivir is recommended for treatment of pandemic influenza in children. The therapy should be started as soon as possible, however, data on the effectiveness of such a treatment is rather limited. This study was accomplished in order to evaluate the effectiveness of oseltamivir depending on the time of the beginning of treatment. Materials and methods. Medical records of 72 children hospitalised to the Vilnius University Children’s Hospital (VUCH) because of laboratory confirmed pandemic influenza during November–December 2009 were analysed retrospectively. Duration of fever and frequency of complications in children treated with oseltamivir starting on days 1–2 and those who were started to treat ≥day 3 from the beginning of flu symptoms were compared to those who did not receive oseltamivir. Results. 40 patients were treated with oseltamivir: 20 children were commenced on treatment within 48 hours of their illness and the other 20 were started on oseltamivir on day 3 or later. 32 children were not treated with oseltamivir. Fever lasted 2.1 ± 0.8 days if the treatment with oseltamivir was started within 48 hours of illness and 4.1 ± 1.9 days if the treatment was started later (p

A substantial recrudescent wave of pandemic influenza A/H1N1 affected the Mexican population from December 1, 2011-March 20, 2012 following a 2-year period of sporadic transmission.We analyzed demographic and geographic data on all hospitalizations with severe acute respiratory infection (SARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by a Mexican social security medical system during April 1, 2009-March 20, 2012. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset.A total of 7569 SARI hospitalizations and 443 in-patient deaths (5.9%) were reported between December 1, 2011, and March 20, 2012 (1115 A/H1N1-positive inpatients and 154 A/H1N1-positive deaths). The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among subjects ≥60 years of age (χ(2) test, p0.0001) and lower among younger age groups (χ(2) test, p0.04) for the 2011-2012 pandemic wave compared to the earlier waves in 2009. The reproduction number of the winter 2011-2012 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009.We documented a substantial increase in the number of SARI hospitalizations during the period December 2011-March 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is consistent with a build-up of immunity among younger populations.

Background: The French military forces had to modify their epidemiological surveillance systems at the time of the 2009 A(H1N1) influenza pandemic. The aim of this article was to present an evaluation of the different systems used. Methods: Two influenza surveillance systems are usually used in the French forces: one permanent ( Surveillance epidemiologique des armees or SEA) and one seasonal ( Systeme militaire d’observation de la grippe or SMOG). The pandemic required the implementation of a daily surveillance system ( Surveillance quotidienne —SQ), which aimed to monitor disrupted activity owing to 2009 A(H1N1) influenza. The qualitative evaluation of these three systems during the period from September 2009 to February 2010 was performed using 11 criteria based on the list defined by Centers for Disease Control and Prevention of Atlanta. Results: Although it included only 30 sentinel units vs. 320 for the other systems, the SMOG system was the best-performing system in terms of relevance, feasibility, efficacy, quality of data, usefulness, acceptability, efficiency and cost/benefits/costs ratio. The SQ proved very expensive in terms of logistics. Conclusion: The SQ did not bring any significant advantage compared with the weekly surveillance schemes. In the eventuality of another similar episode, influenza surveillance could be significantly improved by using the SMOG system extended to more units for better geographical coverage.

The swine-origin new influenza variant A(H1N1) emerged in 2009 and changed the epidemiology of the 2009/2010 influenza season globally and at national level. Aims: The aim of the authors was to analyse the cases of two influenza seasons. Methods: The Medical and Health Sciences Centre of Debrecen University has 1690 beds with 85 000 patients admitted per year. The diagnosis of influenza was conducted using real-time polymerase chain reaction in the microbiological laboratories of the University and the National Epidemiological Centre, according to the recommendation of the World Health Organization. Results: The incidence of influenza was not higher than that observed in the previous season, but two high-risk patient groups were identified: pregnant women and patients with immunodeficiency (oncohematological and organ transplant patients). The influenza vaccine, which is free for high-risk groups and health care workers in Hungary, appeared to be effective for prevention, because in the 2010/2011 influenza season none of the 58 patients who were administered the vaccination developed influenza. Conclusion: It is an important task to protect oncohematological and organ transplant patients. Orv. Hetil., 2012, 153, 649–654.

Syndromic and virological data are routinely collected by many countries and are often the only information available in real time. The analysis of surveillance data poses many statistical challenges that have not yet been addressed. For instance, the fraction of cases that seek healthcare and are thus detected is often unknown. Here, we propose a general statistical framework that explicitly takes into account the way the surveillance data are generated. Our approach couples a deterministic mathematical model with a statistical description of the reporting process and is applied to surveillance data collected in Italy during the 2009–2010 A/H1N1 influenza pandemic. We estimate that the reproduction number R was initially into the range 1.2–1.4 and that case detection in children was significantly higher than in adults. According to the best fit models, we estimate that school-age children experienced the highest infection rate overall. In terms of both estimated peak-incidence and overall attack rate, according to the Susceptibility and Immunity models the 5–14 years age-class was about 5 times more infected than the 65+ years old age-group and about twice more than the 15–64 years age-class. The multiplying factors are doubled using the Baseline model. Overall, the estimated attack rate was about 16% according to the Baseline model and 30% according to the Susceptibility and Immunity models.

Wild type human influenza viruses do not usually grow well in embryonated hens' eggs, the substrate of choice for the production of inactivated influenza vaccine, and vaccine viruses need to be developed specifically for this purpose. In the event of a pandemic of influenza, vaccine viruses need to be created with utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a network of laboratories began a race against time to develop suitable candidate vaccine viruses. Two approaches were followed, the classical reassortment approach and the more recent reverse genetics approach. This report describes the development and the characteristics of current pandemic H1N1 candidate vaccine viruses.

Data derived from epidemiologic surveillance adopted at our center in hematologic and stem cell transplant patients during the 2009 influenza A (H1N1)v pandemic are reported. Of the 52 patients with influenza-like disease we observed, 37 underwent a real-time PCR evaluation and 21 had a confirmed diagnosis. Of the RT-PCR-confirmed cases, 23.8% were children (age 65 years; 47.6% presented with a pulmonary infiltrate and 33.3% with respiratory failure. Pulmonary involvement was observed more frequently in patients with comorbidities. All patients received a course of oseltamivir therapy starting an average of 1 day (range

The pattern of illness associated with the first wave of the pandemic influenza A H1N1 (swine flu) in the spring and early summer of 2009 in regions of the province of Manitoba in Canada was more severe, on a population basis, than any other northern hemisphere jurisdiction outside of Mexico City. Manitoba accounted for 50% of intensive care admissions and 25% of pediatric admissions, but only 6.5% of deaths, attributable to the virus in Canada during the first wave. Activation and use of emergency response protocols embedded within the routine health authority management system and good communication between the diagnostic laboratory, public health, and health care practitioners was effective in coping with the sudden need for hospitalization of large numbers of children and young adults with severe respiratory illness over a short time period. Early treatment with oseltamivir was associated with a shorter duration of hospitalization among children. Intensive education of health care providers, patients, and visitors, along with close monitoring of infection prevention and control practices, were instrumental in preventing both nosocomial and health care worker infections.

INTRODUCTION AND OBJECTIVES: Influenza A is expected to have a great impact in countries in the northern hemisphere yet little has been reported about how this outbreak can affect hospital care. The aim of this study is to assess patients who demand care for flu symptoms and their outcome. MATERIAL AND METHODS: From the beginning of the outbreak a specific protocol was established for the care of patients with potential influenza A in admission, emergency and hospitalization ward. A nominal registry was designed with clinical and epidemiological data. RESULTS: 1018 patients were evaluated for potential influenza A from the beginning of the outbreak until the 31(st) August, 2009. 77% of them fulfilled clinical criteria and were classified as suspected cases. Mean age was 31,7 years (SD17,2), 52% were women, 3,3% pregnant or puerperal. The admission rate was 23,4% with a global mean stay of 3,5 days, and 2,5 for the adults who were admitted to the short stay hospital unit. 2,8 % had pneumonia, two patients required admission to the intensive care unit and one of them died. CONCLUSIONS: Our data show an outbreak with mild illness, with a remarkable percentage of pneumonia but with good outcome. Despite of the high percentage of admissions, and in order to avoid the misleading attention to other patients, we believe that an assistance model based in specific units, short stay and post-discharge follow up could be suitable.

BACKGROUND: The rapidly evolving pandemic of novel 2009 swine-origin influenza A (H1N1) virus (S-OIV) demands that accurate and practical diagnostics be urgently evaluated for their potential clinical utility. OBJECTIVE: To determine the diagnostic accuracy of a rapid influenza diagnostic test (RIDT) and direct fluorescent antibody (DFA) assay for S-OIV by using reverse-transcription polymerase chain reaction (RT-PCR) as the reference standard. METHODS: We prospectively recruited children (aged 0–17 years) assessed in the emergency department of a pediatric referral hospital and a community pediatric clinic for influenza-like illness between May 22 and July 25, 2009. RIDT (performed on-site) and DFA were compared with RT-PCR to determine their sensitivity and specificity for S-OIV. We also compared the sensitivity of RIDT for S-OIV to that for seasonal influenza over 2 preceding seasons. RESULTS: Of 820 children enrolled, 651 were from the emergency department and 169 were from the clinic. RIDT sensitivity was 62% (95% confidence interval [CI]: 52%–70%) for S-OIV, with a specificity of 99% (95% CI: 92%–100%). DFA sensitivity was 83% (95% CI: 75%–89%) and was superior to that of RIDT (P < .001). RIDT sensitivity for S-OIV was comparable to that for seasonal influenza when using DFA supplemented with culture as the reference standard. RIDT sensitivity for influenza viruses was significantly higher in children 5 years of age or younger (P = .003) and in patients presenting ≤2 days after symptom onset (P < .001). CONCLUSIONS: The sensitivity of RIDT for detection of S-OIV is higher than recently reported in mixed adult-pediatric populations but remains suboptimal.

The neuraminidase of the influenza virus is the target of antiviral drugs oseltamivir and zanamivir. Clinical practices have shown that zanamivir and oseltamivir are effective in treating the 2009 A(H1N1) influenza virus. However, drug resistance strains are also emerging. Herein, we report the findings from homology modeling and molecular simulations of 2009 A(H1N1) neuraminidase complexed with zanamivir, oseltamivir, and several herb extracts with potential activities. Our docked oseltamivir and zanamivir results are consistent with previous studies. Based on the same procedure, the docked results of herb extracts HR1039 and HR1040 suggest that they are potential potent inhibitors of neuraminidase. Also, the binding modes of HR1039/HR1040 are different from those of oseltmivir and zanamivir, and may be effective in treating oseltamivir-resistant influenza virus strains.

Sporadic outbreaks of epizootics including SARS coronavirus and H5N1 avian influenza remind us of the potential for communicable diseases to quickly spread into worldwide epidemics. To confront emerging viral threats, nations have implemented strategies to prepare for pandemics and to control virus spread. Despite improved surveillance and quarantine measures, we find ourselves in the midst of a H1N1 influenza pandemic. Effective therapeutics and vaccines are essential to protect against current and future pandemics. The best route to effective therapeutics and vaccines is through a detailed and global view of virus–host interactions that can be achieved using a systems biology approach. Here, we provide our perspective on the role of systems biology in deepening our understanding of virus–host interactions and in improving drug and vaccine development. We offer examples from influenza virus research, as well as from research on other pandemics of our time – HIV/AIDS and HCV – to demonstrate that systems biology offers one possible key to stopping the cycle of viral pandemics.

The origin of the new A (H1N1) influenza virus recently emerging in North America is a hot controversial topic of significance in disease control and risk assessment. Some experts claimed that it was an unusually mongrelized mix of human, avian and swine influenza viruses, while some others concluded that it was totally a simple re-assortment hybrid of two lineages of swine influenza viruses. Here the phylogenetic diversity of the viral PB1, PA and PB2 gene sequences using online web servers, and the results suggest that all the 8 genetic segments of the new virus were possibly from two lineages of swine influenza viruses, and one of the lineage was a mongrelized mix of human, avian and swine influenza viruses emerging in the world approximately 10 years ago. Considering the recent epidemiological trends of the new virus, we believe it will spread more widely in the world and persist long in human populations. It also could spread among swine populations. The future wide spreading of the new virus may coincide the disappearance of a subtype of previous human influenza A virus.

We assessed the perception and attitudes of university staff, including medical school and other science specialties, toward the 2009 A/H1N1 influenza pandemic and influenza vaccination program. A cross-sectional online survey was conducted among 4,529 university personnel on October 19-20, 2009. Seven hundred (15%) employees participated in the study. Only 18% were willing to be vaccinated, men more than women (29% versus 9%, P < 0.001), and professors/researchers more than administrative/technical staff (30% vs. 6%, P < 0.001). Intention to be vaccinated was insufficient. Additional efforts are needed to improve information dissemination among university staff. Medical university personnel should receive more information to increase vaccine coverage and protect them as well as patients.

We report influenza vaccination coverage in target groups for the 2010–2011 influenza season, one year after the A(H1N1) pandemic. Data were collected through a one-stage cross-sectional national random telephone survey conducted in January 2011 among a sample of the population of mainland France connected to a land telephone line. Influenza vaccination coverage was below 75%, ranging from 28% for health professionals to 71% in the “65+” group with an underlying condition. Coverage was higher in the “65+” compared to the “

A recrudescent wave of pandemic influenza A/H1N1 affected Mexico during the winter of 2013-2014 following a mild 2012-2013 A/H3N2 influenza season.We compared the demographic and geographic characteristics of hospitalizations and inpatient deaths for severe acute respiratory infection (SARI) and laboratory-confirmed influenza during the 2013-2014 influenza season compared to previous influenza seasons, based on a large prospective surveillance system maintained by the Mexican Social Security health care system.A total of 14,236 SARI hospitalizations and 1,163 inpatient deaths (8.2%) were reported between October 1, 2013 and March 31, 2014. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 years and lower among younger age groups for the 2013-2014 A/H1N1 season compared to the previous A/H1N1 season in 2011-2012 (χ(2) test, p0.001). The reproduction number for the winter 2013-2014 influenza season in central Mexico was estimated at 1.3-1.4, in line with that reported for the 2011-2012 A/H1N1 season but lower than during the initial waves of pandemic A/H1N1 activity in 2009.We documented a substantial increase in the number of A/H1N1-related hospitalizations and deaths during the period from October 2013-March 2014 in Mexico and a proportionate shift of severe disease to middle-aged adults, relative to the preceding A/H1N1 2011-2012 season. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-2009 pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.

Javier D avila-Torres, Gerardo Chowell, V ictor H. Borja-Aburto, C ecile Viboud, Concepci on Grajalez-Mu~niz, Mark A. Miller Direction of Medical Benefits, Mexican Institute of Social Security, Mexico City, Mexico Division of Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA Mathematical, Computational and Modeling Sciences Center, School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona, USA Coordination of Epidemiological Surveillance and Contingency Support, Mexican Institute of Social Security, Mexico City, Mexico

With the emergence and spread of novel influenza strains having pandemic potential, such as the A(H7N9) outbreak in China in the spring of 2013 and the A(H3N2v) outbreak in the US in the summer of 2012, there is growing need to understand strategies that can slow influenza transmission. One intervention that may reduce influenza transmission1–3 -- albeit with high economic and social cost1,4,5 -- is school closure. However, there are varying estimates of the change in transmission dynamics of influenza during time periods when schools are open compared with periods when they are closed.6,7 Such estimates have been often described within limited populations (such as transmission in a school-based population)8, or with regard to school closures that took place when the influenza epidemic was already declining9. Here we attempt to quantify the potential effect of school closure on influenza transmission in the general population by examining the impact of the beginning of school year on the effective reproductive number of the 2009 A(H1N1) pandemic influenza in several US states.