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The Council of Europe has heavily criticised the World Health Organization, national governments, and EU agencies for their handling of the swine flu pandemic. The parliamentary assembly of the council—the international organisation that protects human rights and the rule of law in Europe—published a draft of a report that reviewed how the H1N1 pandemic was handled. National governments, WHO, and EU agencies had all been guilty of actions that led to a “waste of large sums of public money, and unjustified scares and fears about the health risks faced by the European public,” says the report. The conclusion came in the parliamentary assembly’s social, health and family affairs committee report published on 4 June. The report was prepared by Paul Flynn, socialist member of the assembly and Labour MP for Newport West and approved by the committee ahead of a plenary debate at the end of this month. It says there was overwhelming evidence that the seriousness of the pandemic was vastly over-rated by WHO, which led to a …

Key scientists advising the World Health Organization on planning for an influenza pandemic had done paid work for pharmaceutical firms that stood to gain from the guidance they were preparing. These conflicts of interest have never been publicly disclosed by WHO, and WHO has dismissed inquiries into its handling of the A/H1N1 pandemic as “conspiracy theories.” Deborah Cohen and Philip Carter investigate

The chairman of the external expert review committee examining the World Health Organization’s management of the H1N1 pandemic said the panel wants access to confidential documents between the agency and drug companies. Harvey Fineberg, the head of the 29 member review committee, told reporters at the annual World Health Assembly, “We are aware we will want to have access to certain confidential documents that may be in place here at WHO, or elsewhere.” Mr Fineberg, who is also president of the Institute of Medicine in Washington, added that, “Some of the agreements with industry that we would like to examine have been considered confidential.” These documents include “contractual or letters of understanding with (the pharmaceutical) industry that have been considered private communications,” he said. Dr Fineberg’s remarks …

The 3D-structure of the major surface viral antigen from the recent H1N1 pandemic influenza virus (A/Darwin/2001/2009) was determined to 2.8 Å resolution. The structure was used to analyze changes in the HA that have emerged during the first 11 months of the pandemic and have raised public health concerns. Receptor binding properties of this protein reveals a strict preference for human-type receptors.

Homeless are deprived people of developed countries that have a particularly low vaccine coverage and are exposed to vaccine preventable infectious diseases. We report here the efficiency of a voluntary based one-day snapshot influenza vaccination in homeless shelter of Marseille, France, which allowed to obtain a 46.9% H1N1 pandemic vaccine coverage while at the same time only 6% of the French population has been vaccinated.

A Europe wide investigation will begin this week into the World Health Organization’s decision to label the outbreak of swine flu a “pandemic,” amid allegations that it did so under pressure from drug companies looking to boost demand for their vaccines. The inquiry, launched by the Council of Europe’s parliamentary assembly, will be led by the British Labour MP Paul Flynn and could be concluded as early as June. Speaking after being appointed to the role, Mr Flynn said that he wanted to establish how WHO had assessed the risks from …

The H1N1 pandemic has highlighted the importance of reliable and valid triage instruments for scarce resources during periods of high demand. Christian and colleagues have proposed a triage protocol that utilizes a Sequential Organ Failure Assessment (SOFA) score >11 to exclude patients from critical care resources quoting an associated mortality of more than 90% [1]. We sought to assess the hospital mortality associated with this SOFA threshold and the resource implications of such a triage protocol.

Seasonal influenza virus has been described as an emerging and severe pathogen in immunocompromised hosts. Since the beginning of the 2009 influenza A novel H1N1 pandemic, several series have described the clinical course of the disease in various populations. We report the clinical course of H1N1 2009 infection in 10 immunocompromised patients. Half of the patients received long-term steroid therapy. Disease was characterized by a clinical picture similar to that of non-immunocompromised patients but with prolonged course and higher mortality.

Azerbaijan, Afghanistan, and Mongolia will be the first three countries out of a priority group of 35 poor nations to receive the deliveries of H1N1 pandemic flu vaccines donated by governments and drug companies, a senior World Health Organization official said on 17 December. These first deliveries will be followed by shipments to the rest of the 95 vulnerable nations that do not have access to vaccines, said Keiji Fukuda, WHO’s special adviser on pandemic …

During unexpected infectious disease outbreaks, public health agencies must make effective use of limited resources. Vaccine distribution may be delayed and staggered through time, as underscored by the 2009 H1N1 influenza pandemic. Using a mathematical model parametrized with data from the 2009 H1N1 pandemic, we found that optimal allocations of vaccine among people in different age groups and people with high-risk conditions depends on the schedule of vaccine availability relative to the progress of the epidemic. For the projected schedule of H1N1 vaccine availability, the optimal strategy to reduce influenza-related deaths is to initial target high-risk people, followed by school-aged children (5-17) and then young adults (18-44). The optimal strategy to minimize hospitalizations, however, is to target ages 5-44 throughout the vaccination campaign, with only a tiny amount of vaccine used on high-risk people. We find that optimizing at each vaccine release time independently does not give the overall optimal strategy. In this manuscript, we derive policy recommendations for 2009 H1N1 vaccine allocation using a mathematical model. In addition, our optimization procedures, which consider staggered releases over the entire epidemic altogether, are applicable to other outbreaks where not all supplies are available initially.

Until recently, no European country had included healthy children in the priority groups targeted for vaccination against the H1N1 pandemic virus. But as the outbreak gathers speed and more vaccine becomes available, some countries are now telling families that healthy children—or at least infants—are candidates for vaccination after all. The change of mind did not reassure a jittery public. How many European children will eventually be vaccinated remains to be seen, partly because distrust of the new vaccines is running high.

The World Health Organization expressed heightened concern following the presentation of new evidence on clinical aspects of the H1N1 pandemic by experts from heavily affected countries, which document that “primary viral pneumonia is the most common finding in severe cases and a frequent cause of death.” Experts confirmed that most people infected by the H1N1 pandemic virus do not experience complications and recover within a week. But they also expressed concerns about small subsets of patients who rapidly develop severe progressive pneumonia. Pregnant women, children younger than 2 years old, and …

Epidemiology and public health planning will increasingly rely on the analysis of genetic sequence data. The ongoing influenza A/H1N1 pandemic may represent a tipping point in this trend, with A/H1N1 being the first human pathogen routinely genotyped from the beginning of its spread. To take full advantage of this genetic information, we introduce a novel method to reconstruct the spatiotemporal dynamics of outbreaks from sequence data. The approach is based on a new paradigm were ancestries are inferred directly rather than through the reconstruction of most recent common ancestors (MRCAs) as in phylogenetics. Using 279 A/H1N1 hemagglutinin (HA) sequences, we confirm the emergence of the 2009 flu pandemic in Mexico. The virus initially spread to the US, and then to the rest of the world with both Mexico and the US acting as the main sources. While compatible with current epidemiological understanding of the 2009 H1N1 pandemic, our results provide a much finer picture of the spatiotemporal dynamics. The results also highlight how much additional epidemiological information can be gathered from genetic monitoring of a disease outbreak.

The absence of a full-length PB1-F2 protein has been suggested as one possible determinant for the low pathogenicity of the 2009 Influenza A H1N1 pandemic strain. Since the PB1-F2 sequence of this strain has three stop codons and its ancestors encode a full-length protein, the stop codons must have appeared recently. This suggests that the PB1-F2 protein is not evolutionary and functionally important for the new virus. We investigate the role of this protein in the evolution of influenza A viruses, and in particular in relation to the history of the new strain. We show that its evolutionary history is comparable to other, non-translated, subsequences in the PB1 segment, suggesting that PB1-F2 does not contribute significantly to the fitness of the influenza A virus.

LAST WEEK brought disappointing news in the fight against the novel H1N1 influenza virus. In anticipation of the winter flu season, U.S. health officials had planned to start vaccinating 160 million priority people in October, but they now say vaccine supplies will be limited. “While we hoped to have had 120 million doses, if everything went well, we know we will have at least 45 million doses,” said Bruce Gellin, director of the National Vaccine Program Office at the Department of Health & Human Services, in a televised broadcast. The delay comes from a slow-growing virus used to make the vaccines. Although initial supplies will be low, the five major producers will continue to crank out 20 million doses per week, he pointed out. And progress is being made in testing the needed vaccines. NIH is moving ahead with clinical trials in children, who, along with pregnant women and health care workers, are among the ...

Newsmaker InterviewSince taking charge of the U.S. Food and Drug Administration (FDA) in May, Commissioner Margaret Hamburg has been a whirlwind of activity. FDA is implementing a new law that gives it the authority to regulate tobacco products, taking a key role in the approval of the planned H1N1 pandemic flu vaccine, revamping its food-safety approach, and trying to make the agency's workings more transparent. In an interview with Science last week, she discussed her plans and dismissed rumors that she and Deputy Commissioner Joshua Sharfstein would each manage different FDA functions. The interview has been edited for brevity.

Swine Flu OutbreakWith HIV/AIDS, TB, malaria, and a host of other diseases competing for attention, influenza has never been high on most African countries' priority lists, and getting a handle on the spread of influenza viruses in Africa has long been problematic because laboratories and surveillance have been lacking. But a 2002 outbreak in Madagascar and a similar one in the Democratic Republic of the Congo in 2003 suggest that, with its myriad of problems, Africa—especially south of the Sahara—might be harder hit by the 2009 H1N1 pandemic virus than any other continent. The virus has so far been detected in 16 African countries, and experts fear that the high HIV infection rates in many African countries could worsen the pandemic's impact.

Objective To screen children with influenza like illness or with symptoms of acute respiratory tract infections for influenza A virus infection — post swine flu pandemic era — using rapid influenza diagnostic tests. Methods During two years (2010 & 2011), 1 200 children with influenza like illness or acute respiratory tract infections (according to World Health Organization criteria) were recruited. Their ages ranged from 2-60 months. Nasopharyngeal aspirates specimens were collected from all children for rapid influenza A diagnostic test. Results Influenza A virus rapid test was positive in 47.5% of the children; the majority (89.6%) were presented with lower respiratory tract infections. Respiratory rate and temperature were significantly higher among positive rapid influenza test patients. Conclusions Influenza A virus infection is still a major cause of respiratory tract infections in Egyptian children. It should be considered in all cases with cough and febrile episodes and influenza like symptoms even post swine flu pandemic.

During the H1N1 pandemic, young adults and college students were noted to be susceptible to influenza. Despite the guidelines for post-secondary education issued by the Center for Disease Control and despite informative campaigns implemented by all institutions, young adults still show low immunization rates. This study aims to examine post-secondary students’ perspectives on influenza immunization. A short online questionnaire was designed. The questionnaire included questions about the participants’ age, gender and program of study. Participants were asked if they have recently received the vaccine or if they chose not to, and what were their reasons/views on flu immunization. The study received ethical clearance by St Lawrence College’s (SLC) Research Ethics Board and the online questionnaire was administered via a mass email to all SLC students across the three campuses. Of the 186 participants, 78% were females and 69% were between 18-24 years. 19% of participants reported to receive the vaccination on campus, 38% were vaccinated off-campus, while 43% did not receive the vaccine. The most commonly reported reasons for vaccination among students were being a program requirement (74%) and believing vaccine makes illness milder if they ever contracted the flu (11%). 37% of the non-vaccinating participants perceive the vaccine as unnecessary, while 12% believed that flu vaccine can make them ill. We conclude a significant percentage of students remain unvaccinated and may not view the flu vaccine as important. Misconceptions concerning the flu vaccine exist and providing more clear and accurate information may enhance flu immunization efficiency among students.

International audience; We investigated the potential impact of the 2009 influenza A(H1N1) pandemic on attitudes towards vaccination among people aged 18 to 75 years and living in metropolitan France. We used data from three national telephone surveys conducted on representative samples in 2000, 2005 and 2010 (n=12,256, n=23,931, n=8,573 respectively). In France, unfavourable attitudes towards vaccination in general dramatically increased from 8.5% in 2000 and 9.6% in 2005 to 38.2% in 2010. In 2010, among respondents who held unfavourable attitudes towards vaccination, 50% mentioned specifically their opposition to the influenza A(H1N1) vaccine. The sociodemographic profile associated with these attitudes also changed greatly. In particular, unfavourable attitudes towards vaccination in general became significantly more frequent among less educated people in 2010. These attitudes were also correlated with vaccination behaviours. For example, parents who were unfavourable towards vaccination in general were more likely to report that they had at least one child who did not get the measles-mumps-rubella vaccine. As this shift in attitude may have a significant impact on future vaccination coverage, health authorities should urgently address the vaccine confidence gap.

We analysed mortality among people aged 65 years or older in Navarre, Spain in 2009 and compared it with the mean for the same period of time in the previous three years. In the pandemic weeks 24 to 52 2009 we observed 4.9% more deaths than expected (p=0.0268). Excess mortality occurred during the circulation of seasonal influenza (8.0%, p=0.0367) and the first wave of pandemic influenza (9.9%, p=0.0079). In the second wave of pandemic influenza there was a non-significant excess of deaths (5.2%, p=0.1166). Surveillance of laboratory-confirmed severe influenza cases detected only one death in this age group.

Cette note de recherche examine les politiques de santé publique et de sécurité sanitaire mises en place au Canada lors de la pandémie de H1N1 de 2009-2010 afin de les replacer dans le cadre plus large de la gouvernance globale de la santé. En nous intéressant aux critiques et aux recommandations exprimées par rapport à l’expérience canadienne de la pandémie de H1N1, nous cherchons à analyser les réponses politiques du Canada au regard de la gestion de cette crise sanitaire. Nous établissons à cette fin un parallèle entre les évaluations canadiennes de la gestion de cette pandémie et celles effectuées par d’autres pays et organisations. Nous appuyant sur une analyse des rapports d’évaluation canadiens de cette crise, et en les replaçant dans le contexte des critiques internationales portées à l’oms, nous soutenons que le Canada, dans un contexte de mondialisation des risques sanitaires et de multiplication des acteurs internationaux, n’a pas été en mesure de prendre en compte adéquatement le rôle du secteur privé dans les politiques de santé publique ainsi que ses conséquences pour la nature de la gouvernance sanitaire., This research note examines the Canadian public health and security policies during the 2009-2010 H1N1 pandemic in order to situate them in the broader context of global health governance. By focusing on criticisms and recommendations expressed in relation to the Canadian experience of the management of the H1N1 pandemic, we seek to analyze the policy responses of Canada regarding this health crisis by establishing a comparison between the Canadian assessments of the pandemic and those made by other countries and organizations. By analysing Canadian evaluation reports, and situating them in the broader context of the international criticisms made to who, we argue that, in the context of the globalization of health risks and the proliferation of transnational actors, Canada has not been able to adequately take into account the role of the private sector in public health policies as well as its consequences on the nature of health governance., La presente nota de investigación examina las políticas de salud pública y de seguridad sanitaria desplegadas en Canadá durante la pandemia de H1N1 de 2009-2010 con el fin de situarlas en el marco más amplio de la gobernanza mundial de la salud. Partiendo de las críticas y las recomendaciones emitidas sobre la experiencia canadiense con respecto a la pandemia de H1N1, se comparan las repuestas políticas de Canadá en la gestión de esta pandemia a las políticas adoptadas por otros países u organizaciones. El análisis de los informes de evaluación canadienses de la crisis en el contexto de las críticas internacionales enviadas a la OMS permite concluir que, en un contexto de mundialización de los riesgos sanitarios y de multiplicación de los actores internacionales, Canadá no estuvo en capacidad de entender adecuadamente el papel del sector privado en las políticas de salud pública y sus consecuencias sobre la gobernanza sanitaria.

Background High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009–2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009–2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of $1.0 B compared to PCV7. Conclusions In a flu pandemic similar to the 2009–2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs.

Background: The recent influenza A/H1N1 pandemic has caused considerable morbidity and some mortality and is therefore a severe threat to certain individuals. Up to 31 January 2010, there had been 1,229 confirmed deaths from Influenza A/H1N1 in India. Methodology: This study was a retrospective analysis of deaths caused by RT-PCR-confirmed cases of Influenza A/H1N1 in a tertiary care institution in North India from September 2009 until January 2010. Results: Among 125 patients admitted to the Influenza A/H1N1 ward of the hospital, a total of 16 deaths had occurred in patients who were positive for Influenza A/H1N1. Two deaths were in the paediatric age group. Most patients who died had some predisposing illness, such as pregnancy, underlying chronic respiratory illness, diabetes, obesity, etc. Conclusions: In the present study, deaths from Influenza A/H1N1, as with seasonal influenza, appeared to occur primarily in individuals with underlying illness. In India, such individuals may be considered first for preventive strategies, including vaccination.

Influenza vaccination is the most effective method of preventing influenza and its complications. In the 2009 influenza A (H1N1) pandemic, monovalent strain-specific pandemic vaccines were developed rapidly. However, they were only available in limited supply at the initial stage of the vaccination campaign. Thus, tiered use of vaccines, after careful prioritization and determination of dose per individual, was important to maximize the benefit of the available doses. In this study, the principles and methods of epidemiological evaluation of influenza vaccines were investigated, focusing on the immunogenicity and effectiveness. The results of the study of the 2009/H1N1 pandemic will then be detailed.

BACKGROUND: The use of neuraminidase inhibitors (oseltamivir and zanamivir) for the treatment of ill individuals has been an important intervention during the 2009 H1N1 pandemic. However, the emergence and spread of drug resistance remains a major concern and, therefore, optimizing antiviral strategies is crucial to retain the long-term effectiveness of these pharmaceutical interventions.METHODS: A dynamic model of disease transmission was developed to investigate optimal scenarios for the use of a secondary drug (eg, zanamivir). Considering both small and large stockpiles, attack rates were projected by simulating the model to identify ‘tipping points’ for switching to zanamivir as resistance to oseltamivir develops.RESULTS: The use of a limited stockpile of zanamivir can substantially reduce the overall attack rate during pandemic outbreaks. For a reasonably large stockpile of zanamivir, it is optimal to delay the use of this drug for a certain amount of time during which oseltamivir is used as the primary drug. For smaller stockpiles, however, earlier use of zanamivir will be most effective in reducing the overall attack rate. Given a limited stockpile of zanamivir (1.8% in the Canadian plan) without replenishment, and assuming that the fraction of ill individuals being treated is maintained below 60%, the results suggest that zanamivir should be dispensed as the primary drug for thresholds of the cumulative number of oseltamivir resistance below 20%.INTERPRETATION: Strategic use of a secondary drug becomes crucial for pandemic mitigation if vaccination and other interventions fail to sufficiently reduce disease transmission in the community. These findings highlight the importance of enhanced surveillance and clinical monitoring for rapid identification of resistance emergence and its population incidence, so that optimal timing for adaptation to the use of drugs can be achieved.

Background The prevalence and severity of the 2009 H1N1 pandemic appeared to vary significantly across populations and geographic regions. We sought to investigate the variability in transmissibility of H1N1 pandemic in different health regions (including urban centres and remote, isolated communities) in the province of Manitoba, Canada. Methods The Richards model was used to fit to the daily number of laboratory-confirmed cases and estimate transmissibility (referred to as the basic reproduction number, R0), doubling times, and turning points of outbreaks in both spring and fall waves of the H1N1 pandemic in several health regions. Results We observed considerable variation in R0 estimates ranging from 1.55 to 2.24, with confidence intervals ranging from 1.45 to 2.88, for an average generation time of 2.9 days, and shorter doubling times in some remote and isolated communities compared to urban centres, suggesting a more rapid spread of disease in these communities during the first wave. For the second wave, Re, the effective reproduction number, is estimated to be lower for remote and isolated communities; however, outbreaks appear to have been driven by somewhat higher transmissibility in urban centres. Conclusions There was considerable geographic variation in transmissibility of the 2009 pandemic outbreaks. While highlighting the importance of estimating R0 for informing health responses, the findings indicate that projecting the transmissibility for large-scale epidemics may not faithfully characterize the early spread of disease in remote and isolated communities.

Antigenic variation of influenza virus hemagglutinin (HA) remains the principal challenge in developing more effective vaccines. Here, we report determination of the 3D structures of HA trimers on intact 2009 H1N1 pandemic virus particles in the absence and presence of neutralizing antibodies. We studied HA trimer structures bound to H17-L10, an antibody that recognizes a quaternary epitope near the head region of the trimer, and to C179, a broadly neutralizing antibody that is reactive to the conserved stem region of HA and neutralizes viruses expressing a broad range of HA subtypes (H1, H2, H5, and H9). We deduce the locations of the molecular surfaces of HA involved in interaction with each of these antibodies. Despite the dense packing of HA trimers on the viral surface, and the location of the stem region close to the viral membrane, we show that ∼75% of HA trimers have C179 bound to the stem domain. Thus, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, suggesting that universal influenza vaccines that elicit such antibodies could be effective.View Large Image | View Hi-Res Image | Download PowerPoint Slide