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J Clin Virol. 2009 Dec 2.
Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan
during the 2008-2009 season.

Baranovich T, Saito R, Suzuki Y, Zaraket H, Dapat C, Caperig-Dapat I, Oguma T, Shabana II, Saito T, Suzuki H; the Japanese Influenza Collaborative Study Group. Division of Public Health, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-Dori, Chuoku, Niigata City, Niigata Prefecture 951-8510, Japan. BACKGROUND: A substantial increase in oseltamivir-resistant A(H1N1) influenza viruses
was reported in Europe in late 2007. OBJECTIVES: To monitor the antiviral susceptibility
profile of human A(H1N1) influenza viruses in Japan during the 2007-2008 and 2008-2009 seasons. STUDY DESIGN: Viruses were obtained from respiratory samples of patients with
influenza collected in Japan between December 2007 and April 2008 (n=1046) and between December 2008 and April 2009 (n=1789). Oseltamivir resistance was determined by an H274Y-specific real-time PCR cycling probe assay and a neuraminidase inhibition assay. Amantadine resistance was assessed by sequencing the M2 gene. Sequencing of the hemagglutinin and NA genes was performed to infer phylogenetic relationships between different strains. RESULTS: Three of 687 (0.4%) A(H1N1) viruses from the 2007-2008 season and 745 of 745 (100%) viruses from the 2008-2009 season carried the NA-H274Y substitution and demonstrated a >300-fold reduction in oseltamivir susceptibility. All oseltamivir-resistant viruses from the 2008-2009 season possessed an A193T substitution in the receptor-binding domain of the hemagglutinin. Amantadine resistance was detected in 431 of 687 (62.7%) and 0 of 745 (0.0%) of the A(H1N1) viruses from the 2007-2008 and 2008-2009 seasons, respectively. CONCLUSIONS: A dramatic surge in oseltamivir-resistant A(H1N1) viruses possessing the NA-H274Y substitution was detected in Japan during the 2008-2009 season. The emergence of oseltamivir-resistant viruses was facilitated by mutations in the viral genome. Intensified surveillance, including phenotypic assays and sequencing of the hemagglutinin, neuraminidase, and M2 gene would allow monitoring of the spread and evolution of drug-resistant influenza virus variants. PLoS One. 2009 Dec 3;4(12):e8164.
Adaptive vaccination strategies to mitigate pandemic influenza: Mexico as a
case study.

Chowell G, Viboud C, Wang X, Bertozzi SM, Miller MA. Mathematical, Computational & Modeling Sciences Center, School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona, United States of America. BACKGROUND: We explore vaccination strategies against pandemic influenza in Mexico
using an age-structured transmission model calibrated against local epidemiological data from the Spring 2009 A(H1N1) pandemic. METHODS AND FINDINGS: In the context of
limited vaccine supplies, we evaluate age-targeted allocation strategies that either prioritize youngest children and persons over 65 years of age, as for seasonal influenza, or adaptively prioritize age groups based on the age patterns of hospitalization and death monitored in real-time during the early stages of the pandemic. Overall the adaptive vaccination strategy outperformed the seasonal influenza vaccination allocation strategy for a wide range of disease and vaccine coverage parameters. CONCLUSIONS: This modeling approach could
inform policies for Mexico and other countries with similar demographic features and vaccine resources issues, with regard to the mitigation of the S-OIV pandemic. We also discuss logistical issues associated with the implementation of adaptive vaccination strategies in the context of past and future influenza pandemics. Eur J Radiol. 2009 Dec 3.
High-resolution computed tomography findings from adult patients with
Influenza A (H1N1) virus-associated pneumonia.

Marchiori E, Zanetti G, Hochhegger B, Rodrigues RS, Fontes CA, Nobre LF, Mançano AD, Fluminense Federal University, Rio de Janeiro, Brazil; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. OBJECTIVE: The aim of this study was to assess the high-resolution computed tomography
(HRCT) findings at presentation in patients diagnosed with Influenza A (H1N1) virus- associated pneumonia. MATERIALS AND METHODS: We reviewed the HRCT findings from
20 patients diagnosed with Influenza A (H1N1) and compared their HRCT scans with chest radiographs, obtained on the same day. The imaging studies were obtained 4-9 days after the onset of symptoms. The patients included 11 men and 9 women (ages 24-62 years; mean 42.7 years). All patients had a body temperature greater than 100.4 degrees F (>38 degrees C), tachypnea, and cough. Other common symptoms included diarrhea (60%) and sore throat (30%). The radiographs and HRCT scans were reviewed independently by two observers who reached a consensus decision. RESULTS: The predominant HRCT findings
consisted of bilateral ground-glass opacities (n=12), bilateral areas of consolidation (n=2), or a mixed bilateral pattern of ground-glass opacities and areas of consolidation (n=6). The abnormalities were bilateral in all of the 20 patients, had a predominantly sub-pleural distribution in 13 patients, and had a random distribution in the remaining 7 patients. The predominant radiographic findings were consolidations. Normal radiographs were found in 4 out of the 20 patients. CONCLUSION: HRCT may reveal parenchymal abnormalities in
patients with Influenza A (H1N1) infection who have normal findings on radiographs. The predominant HRCT findings were bilateral, peripheral, ground-glass opacities and/or bilateral areas of consolidation. The patients who presented consolidations had more severe clinical PLoS One. 2009 Dec 3;4(12):e8032.
Early assessment of anxiety and behavioral response to novel swine-origin influenza A(H1N1).Jones JH, Salathé M. Department of Anthropology, Stanford University, Stanford, California, United States of America. BACKGROUND: Since late April, 2009, a novel influenza virus A (H1N1), generally referred
to as the "swine flu," has spread around the globe and infected hundreds of thousands of people. During the first few days after the initial outbreak in Mexico, extensive media coverage together with a high degree of uncertainty about the transmissibility and mortality rate associated with the virus caused widespread concern in the population. The spread of an infectious disease can be strongly influenced by behavioral changes (e.g., social distancing) during the early phase of an epidemic, but data on risk perception and behavioral response to a novel virus is usually collected with a substantial delay or after an epidemic has run its course. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results
from an online survey that gathered data (n = 6,249) about risk perception of the Influenza A(H1N1) outbreak during the first few days of widespread media coverage (April 28-May 5, 2009). We find that after an initially high level of concern, levels of anxiety waned along with the perception of the virus as an immediate threat. Overall, our data provide evidence that emotional status mediates behavioral response. Intriguingly, principal component analysis revealed strong clustering of anxiety about swine flu, bird flu and terrorism. All three of these threats receive a great deal of media attention and their fundamental uncertainty is likely to CONCLUSIONS/SIGNIFICANCE: Our results suggest that respondents' behavior varies in
predictable ways. Of particular interest, we find that affective variables, such as self-reported anxiety over the epidemic, mediate the likelihood that respondents will engage in protective behavior. Understanding how protective behavior such as social distancing varies and the specific factors that mediate it may help with the design of epidemic control strategies. Vaccine. 2009 Dec 4.
Exposure to MF59-adjuvanted influenza vaccines during pregnancy-A
retrospective analysis.

Tsai T, Kyaw MH, Novicki D, Nacci P, Rai S, Clemens R. Novartis Vaccines and Diagnostics, Cambridge, MA, USA. Pregnant women are at increased risk for complications and death associated with pandemic H1N1 influenza infection and they are prioritized for vaccination by public health authorities. Few data are available on the safety of adjuvants as components of pandemic vaccines that could be given systematically to pregnant women. Here we review nonclinical and clinical data on pregnancy outcomes associated with exposure to MF59((R)), an adjuvant used in candidate H1N1 pandemic vaccines. Evaluation of the reproductive and developmental toxicity of MF59 alone and of a candidate MF59-adjuvanted H5N1 vaccine in animals demonstrated no evidence of teratogenicity or impact on fetal development. The clinical trial database encompassing all Novartis Vaccine studies from 1991 to 2009 was searched to compare pregnancy outcomes in subjects exposed to MF59-adjuvanted or unadjuvanted influenza vaccines. Analysis of the clinical trial database found that the distribution of pregnancy outcomes (normal, abnormal, or ending in therapeutic abortion) was similar in subjects exposed to MF59-adjuvanted and unadjuvanted influenza vaccine at any time in pregnancy and also, specifically, in early pregnancy: the respective proportions reported as a normal pregnancy outcome were 70% and 75%, respectively, overall, and 61% and 68%, respectively, in early pregnancy. Although data from the clinical database are too few to draw definitive conclusions on risks associated with exposure to MF59-adjuvanted influenza vaccines during pregnancy, available observations, so far, indicate no signals of a risk. Further data will be forthcoming from planned post-licensure studies of adjuvanted H1N1 Am J Epidemiol. 2009 Dec 4.
Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in
the Vaccine Safety Datalink Project.

Greene SK, Kulldorff M, Lewis EM, Li R, Yin R, Weintraub ES, Fireman BH, Lieu TA, Nordin JD, Glanz JM, Baxter R, Jacobsen SJ, Broder KR, Lee GM. The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06-2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillian-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza PLoS Med. 2009 Dec;6(12):e1000207.
The severity of pandemic H1N1 influenza in the United States, from April to
July 2009: a Bayesian analysis.

Presanis AM, De Angelis D; New York City Swine Flu Investigation Team, Hagy A, Reed C, Riley S, Cooper BS, Finelli L, Biedrzycki P, Lipsitch M.(Medical Research Council Biostatistics Unit, BACKGROUND: Accurate measures of the severity of pandemic (H1N1) 2009 influenza
(pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. METHODS AND FINDINGS: We used
complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data--medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York--were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-9 x lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. CONCLUSIONS: These estimates suggest that an autumn-winter pandemic wave of pH1N1
with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than Proc Natl Acad Sci U S A. 2009 Dec 7.
Adaptive strategies of the influenza virus polymerase for replication in

Mehle A, Doudna JA.(Departments of Molecular and Cell Biology and Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, CA 94705). Transmission of influenza viruses into the human population requires surmounting barriers to cross- species infection. Changes in the influenza polymerase overcome one such barrier. Viruses isolated from birds generally contain polymerases with the avian-signature glutamic acid at amino acid 627 in the PB2 subunit. These polymerases display restricted activity in human cells. An adaptive change in this residue from glutamic acid to the human-signature lysine confers high levels of polymerase activity in human cells. This mutation permits escape from a species-specific restriction factor that targets polymerases from avian viruses. A 2009 swine-origin H1N1 influenza A virus recently established a pandemic infection in humans, even though the virus encodes a PB2 with the restrictive glutamic acid at amino acid 627. We show here that the 2009 H1N1 virus has acquired second-site suppressor mutations in its PB2 polymerase subunit that convey enhanced polymerase activity in human cells. Introduction of this polymorphism into the PB2 subunit of a primary avian isolate also increased polymerase activity and viral replication in human and porcine cells. An alternate adaptive strategy has also been identified, whereby introduction of a human PA subunit into an avian polymerase overcomes restriction in human cells. These data reveal a strategy used by the 2009 H1N1 influenza A virus and identify other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans. Eur J Health Econ. 2009 Dec 9.
The macroeconomic impact of pandemic influenza: estimates from models of
the United Kingdom, France, Belgium and The Netherlands.

Keogh-Brown MR, Smith RD, Edmunds JW, Beutels P. Health Policy Unit, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK, The 2003 outbreak of severe acute respiratory syndrome (SARS) showed that infectious disease outbreaks can have notable macroeconomic impacts. The current H1N1 and potential H5N1 flu pandemics could have a much greater impact. Using a multi-sector single country computable general equilibrium model of the United Kingdom, France, Belgium and The Netherlands, together with disease scenarios of varying severity, we examine the potential economic cost of a modern pandemic. Policies of school closure, vaccination and antivirals, together with prophylactic absence from work are evaluated and their cost impacts are estimated. Results suggest GDP losses from the disease of approximately 0.5-2% but school closure and prophylactic absenteeism more than triples these effects. Increasing school closures from 4 weeks at the peak to entire pandemic closure almost doubles the economic cost, but antivirals and vaccinations seem worthwhile. Careful planning is therefore important to ensure expensive policies to mitigate the pandemic are effective in minimising Arch Virol. 2009 Dec 10.
Subtype identification of the novel A H1N1 and other human influenza A
viruses using an oligonucleotide microarray.

Kang X, Li Y, Sun H, Wu W, Liu H, Lin F, Qing C, Chang G, Zhu Q, Chen W, Yang Y. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Dongdajie Road 20, Fengtai District, 100071, Beijing, China. A novel strain of influenza A (H1N1) virus was isolated in Mexico and the US in March and April 2009. This novel virus spread to many countries and regions in a few months, and WHO raised the level of pandemic alert from phase 5 to phase 6 on June 11, 2009. The accurate identification of H1N1 virus and other human seasonal influenza A viruses is very important for further treatment and control of their infections. In this study, we developed an oligonucleotide microarray to subtype human H1N1, H3N2 and H5N1 influenza viruses, which could distinguish the novel H1N1 from human seasonal H1N1 influenza viruses and swine H1N1 influenza viruses. The microarray utilizes a panel of primers for multiplex PCR amplification of the hemagglutinin (HA), neuraminidase (NA) and matrix (MP) genes of human influenza A viruses. The 59-mer oligonucleotides were designed to distinguish different subtypes of human influenza A viruses. With this microarray, we accurately identified and correctly subtyped the reference virus strains. Moreover, we confirmed 4 out of 39 clinical throat swab specimens from suspected cases of novel H1N1. AJN, American Journal of Nursing:
12, December 2009

Nurses, the 2009 H1n1 Flu, and Seasonal Vaccination
Aschenbrenner, Diane S. MS, APRN,BC
* Nurses play an important role in flu prevention, especially with the reemergence of the 2009 H1N1 pandemic influenza (swine flu). * Because the H1N1 strain was identified after the seasonal flu vaccine was developed, patients and health care providers should be immunized for both. * Priority populations for 2009 H1N1 flu vaccination are pregnant women, people who live with or provide care to infants younger than six months old, health care providers, people between six months and 24 years old, and people 25 to 64 years old with medical conditions that increase their risk of complications from the flu. * Most flu vaccines are administered by intramuscular injection. An intranasal spray is also available for use in patients two to 49 years old (except pregnant women).


Successful augmentation of clozapine-resistant treatment of schizophrenia with clonidine

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Impftod und impfschaden durch virus-mythen, p. schmidt, 02.10.2009

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