Impact of Anti-T-Cell Therapy in the Immunogenicity of Seasonal Influenza Vaccine in Kidney Transplant Recipients.

BACKGROUND: The influence of anti-T-cell therapy in the immunogenicity of the influenza vaccine in kidney transplant recipients remains unclear. METHODS: During the 2010 to 2011 influenza season, we evaluated the immune response to the inactivated trivalent influenza vaccine in kidney transplant recipients having received Thymoglobulin or basiliximab as induction therapy. A hemagglutination inhibition assay was used to assess the immunogenicity of the vaccine. The primary outcome was geometric mean titers of hemagglutination inhibition after influenza vaccination. RESULTS: Sixty patients (Thymoglobulin n=22 and basiliximab n=38) were included. Patients in the Thymoglobulin group were older (P=0.16), showed higher creatinine levels (P=0.16) and had more frequently received a previous transplant (P=0.02). There were no significant differences in geometric mean titers for any of the three viral strains between groups (P=0.69 for H1N1, P=0.56 for H3N2, and P=0.7 for B strain). Seroconversion to at least one viral strain was seen in 15 (68%) of 22 patients in the Thymoglobulin group and 28 (73%) of 38 in the basiliximab group (P=0.77). In patients vaccinated during the first year after receiving anti-T-cell therapy (n=25), there was a trend toward lower vaccine responses in the Thymoglobulin group. Patients who received Thymoglobulin showed lower CD4 cell counts and lower levels of IgM, at an average of 16.2 months after transplantation. A multivariate analysis showed that only the absence of mycophenolate was associated with a better vaccine response (odds ratio=9.47; 95% confidence interval, 1.03-86.9; P=0.047). CONCLUSION: No significant differences were seen in immunogenicity of the influenza vaccine in kidney transplant recipients having received either Thymoglobulin or basiliximab.

Dynamic social representations of the 2009 H1N1 pandemic: Shifting patterns of sense-making and blame

We investigate dynamics of public perceptions of the 2009 H1N1 influenza pandemic to understand changing patterns of sense-making and blame regarding the outbreak of emerging infectious diseases. We draw on social representation theory combined with a dramaturgical perspective to identify changes in how various collectives are depicted over the course of the pandemic, according to three roles: heroes, villains and victims. Quantitative results based on content analysis of three cross-sectional waves of interviews show a shift from mentions of distant collectives (e.g., far-flung countries) at Wave 1 to local collectives (e.g., risk groups) as the pandemic became of more immediate concern (Wave 2) and declined (Wave 3). Semi-automated content analysis of media coverage shows similar results. Thematic analyses of the discourse associated with collectives revealed that many were consistently perceived as heroes, villains and victims.

A Randomized Controlled Trial Comparing Intradermal vs. Intramuscular Influenza Vaccine in Lung Transplant Recipients

Background: Immunogenicity of standard infl uenza vaccine is suboptimal in lung transplant recipients. Intradermal vaccine may elicit stronger responses due to recruitment of local dendritic cells. We compared the immunogenicity of the infl uenza vaccine administered intradermally (ID) to the standard intramuscular (IM) vaccination. Methods: In this investigator-blinded, two-center, prospective trial, lung transplant patients were randomized to receive intradermal (6ug) or intramuscular (15ug) 2008/9 trivalent inactivated infl uenza vaccine. Immunogenicity was evaluated using a standard hemagglutination inhibition assay (HIA). Response to the vaccine was defi ned as a fourfold increase of the HIA levels for any of the 3 viral strains in the vaccine. Geometric mean titers (GMT) and seroprotection rate (HIA ≥32) were also analyzed. Patients were followed during 6 months for the development of infl uenza or acute rejection. Results: We randomized 84 patients to receive the ID (n=41) vs. IM (n=43) vaccine, respectively. Baseline characteristics were similar between groups. Median time from transplantation was 3.4 yrs (ID) vs. 3.3 yrs (IM) (p=0.84). Vaccine response to at least one antigen was seen in 6/41 (14.6%) patients in the ID vs. 8/43 (18.6%) in the IM group (p=0.77). In the ID group, GMTs (95% CI) after vaccination were 15.7 (11.1-22.3) for H1N1, 84.0 (52.0-135.7) for H3N2, and 14.5 (9.6-21.8) for B strains vs. in the IM group 17.5 (11.8-25.9) for H1N1, 108.9 (77.5-153.2) for H3N2, and 20.2 (12.8-31.9) for B (p=NS, all 3 strains). Seroprotection was 39% (H1N1), 82.9% (H3N2) and 29.3% (B strain) in the ID group vs. 27.9% (H1N1), 97.7% (H3N2) and 58.1% (B strain) in the IM group. No factors associated with vaccine response were identifi ed. Mild adverse events were seen in 44% of patients (ID) vs. 34% (IM) (p=0.38). Two patients (4.8%) in the ID group developed infl uenza infection compared to none in the IM group. Two patients in each group developed biopsy-proven acute rejection during follow-up. Conclusions: Immunogenicity of the 2008/09 infl uenza vaccine was poor in lung transplant recipients. ID administration of the vaccine elicited similar immune responses to standard IM vaccination. Novel strategies of vaccination are needed to protect lung transplant recipients from infl uenza.

OpenFluDB, a database for human and animal influenza virus.

Although research on influenza lasted for more than 100 years, it is still one of the most prominent diseases causing half a million human deaths every year. With the recent observation of new highly pathogenic H5N1 and H7N7 strains, and the appearance of the influenza pandemic caused by the H1N1 swine-like lineage, a collaborative effort to share observations on the evolution of this virus in both animals and humans has been established. The OpenFlu database (OpenFluDB) is a part of this collaborative effort. It contains genomic and protein sequences, as well as epidemiological data from more than 27,000 isolates. The isolate annotations include virus type, host, geographical location and experimentally tested antiviral resistance. Putative enhanced pathogenicity as well as human adaptation propensity are computed from protein sequences. Each virus isolate can be associated with the laboratories that collected, sequenced and submitted it. Several analysis tools including multiple sequence alignment, phylogenetic analysis and sequence similarity maps enable rapid and efficient mining. The contents of OpenFluDB are supplied by direct user submission, as well as by a daily automatic procedure importing data from public repositories. Additionally, a simple mechanism facilitates the export of OpenFluDB records to GenBank. This resource has been successfully used to rapidly and widely distribute the sequences collected during the recent human swine flu outbreak and also as an exchange platform during the vaccine selection procedure. Database URL: http://openflu.vital-it.ch.

Assessing small non-zero perceptions of chance: The case of H1N1 (swine) flu risks

Feelings of invulnerability, seen in judgments of 0% risk, can reflect misunderstandings of risk and risk behaviors, suggesting increased need for risk communication. However, judgments of 0% risk may be given by individuals who feel invulnerable, and by individuals who are rounding from small non-zero probabilities. We examined the effect of allowing participants to give more precise responses in the 0-1% range on the validity of reported probability judgments. Participants assessed probabilities for getting H1N1 influenza and dying from it conditional on infection, using a 0-100% visual linear scale. Those responding in the 0-1% range received a follow-up question with more options in that range. This two-step procedure reduced the use of 0% and increased the resolution of responses in the 0-1% range. Moreover, revised probability responses improved predictions of attitudes and self-reported behaviors. Hence, our two-step procedure allows for more precise and more valid measurement of perceived invulnerability. [Authors]

Who knew? Awareness of being recommended for influenza vaccination among US adults

Please cite this paper as: Maurer et al. (2012) Who knew? Awareness of being recommended for influenza vaccination among US adults. Influenza and Other Respiratory Viruses 6(4), 284-290. Background  Starting with the 2010-2011 influenza season, the Advisory Committee on Immunization Practices at the US Centers for Disease Control and Prevention recommends annual influenza vaccination to all people aged 6 months and older unless contraindicated. Objectives  To measure perceived influenza vaccination recommendation status among US adults (n = 2122) and its association with socio-demographic characteristics and recommendation status during the 2009-2010 pandemic influenza season. Methods  We analyze nationally representative data from longitudinal Internet surveys of US adults conducted in November-December 2009 and September-October 2010. Results  During the 2010-2011 vaccination season, 46·2 percent (95%-CI: 43·3-49·1%) of US adults correctly reported to be covered by a government recommendation for influenza vaccination. Awareness of being covered by a government influenza vaccination recommendation was statistically significantly higher among non-working adults and adults who had been recommended for seasonal vaccination or both seasonal and H1N1 vaccination during the 2009-2010 pandemic influenza vaccination season. Conclusion  Our results highlight that a majority of US adults do not know that they are recommended for annual influenza vaccination by the government. The fraction of adults who are unaware of their recommendation status is especially large among newly recommended healthy young adults. The universal vaccination recommendations will only be successful if they reach both patients and physicians and lead to changing vaccination practices. The universal nature of the new recommendation simplifies vaccination-related outreach and compliance with government vaccination guidelines considerably, as it does not require any identification of specific recommendation groups based on complex personal or health risk factors.

Trust in medical organizations predicts pandemic (H1N1) 2009 vaccination behavior and perceived efficacy of protection measures in the Swiss public

Following the recent avian influenza and pandemic (H1N1) 2009 outbreaks, public trust in medical and political authorities is emerging as a new predictor of compliance with officially recommended protection measures. In a two-wave longitudinal survey of adults in French-speaking Switzerland, trust in medical organizations longitudinally predicted actual vaccination status 6 months later, during the pandemic (H1N1) 2009 vaccination campaign. No other variables explained significant amounts of variance. Trust in medical organizations also predicted perceived efficacy of officially recommended protection measures (getting vaccinated, washing hands, wearing a mask, sneezing into the elbow), as did beliefs about health issues (perceived vulnerability to disease, threat perceptions). These findings show that in the case of emerging infectious diseases, actual behavior and perceived efficacy of protection measures may have different antecedents. Moreover, they suggest that public trust is a crucial determinant of vaccination behavior and underscore the practical importance of managing trust in disease prevention campaigns.

Differences in pandemic influenza vaccination policies for pregnant women in Europe.

BACKGROUND: An important component of the policy to deal with the H1N1 pandemic in 2009 was to develop and implement vaccination. Since pregnant women were found to be at particular risk of severe morbidity and mortality, the World Health Organization and the European Centers for Disease Control advised vaccinating pregnant women, regardless of trimester of pregnancy. This study reports a survey of vaccination policies for pregnant women in European countries. METHODS: Questionnaires were sent to European competent authorities of 27 countries via the European Medicines Agency and to leaders of registries of European Surveillance of Congenital Anomalies in 21 countries. RESULTS: Replies were received for 24 out of 32 European countries of which 20 had an official pandemic vaccination policy. These 20 countries all had a policy targeting pregnant women. For two of the four countries without official pandemic vaccination policies, some vaccination of pregnant women took place. In 12 out of 20 countries the policy was to vaccinate only second and third trimester pregnant women and in 8 out of 20 countries the policy was to vaccinate pregnant women regardless of trimester of pregnancy. Seven different vaccines were used for pregnant women, of which four contained adjuvants. Few countries had mechanisms to monitor the number of vaccinations given specifically to pregnant women over time. Vaccination uptake varied. CONCLUSIONS: Differences in pandemic vaccination policy and practice might relate to variation in perception of vaccine efficacy and safety, operational issues related to vaccine manufacturing and procurement, and vaccination campaign systems. Increased monitoring of pandemic influenza vaccine coverage of pregnant women is recommended to enable evaluation of the vaccine safety in pregnancy and pandemic vaccination campaign effectiveness.

Pandemic influença A (H1N1) infection in pregnant and nonpregnant women in Spain (2009-2010)

The present study aimed to compare the main features of infection with pandemic influenza A virus in pregnant and nonpregnant women admitted to hospitals in Spain during the first waves of the 2009-2010 influenza pandemic. This was a prospective (November 2009 to June 2010), multicenter observational study. All cases were women of reproductive age who had not been vaccinated against seasonal or pandemic influenza A. Influenza infection was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The sociodemographic and clinical data of all cases were reviewed. A total of 219 inpatients, including 49 pregnant women and 170 nonpregnant women, were enrolled in the study upon admission to participating hospitals. The most substantially different symptoms between the groups were respiratory distress and unilobar consolidation, both of which were more frequent among nonpregnant women. Antibiotics and systemic corticosteroids were more frequently used in nonpregnant women; however, there were no differences in the rates of treatment with antivirals. Our findings indicated that the compared with nonpregnant women, pregnant women in this study did not have significantly different symptoms and were not at increased risk of complications from pandemic influenza virus infection.

The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.

UNLABELLED: Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivityin vitro Recently, we reported that inactivation of a single HA-activating protease gene,Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection ofTmprss2knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion ofTmprss4alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast,Tmprss2(-/-)Tmprss4(-/-)double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virusin vivo IMPORTANCE: Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously thatTmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes,Tmprss2andTmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza virusesin vivo.

Transcriptional approach to study porcine tracheal epithelial cells individually or dually infected with swine influenza virus and Streptococcus suis

Background: Swine influenza is a highly contagious viral infection in pigs affecting the respiratory tract that can have significant economic impacts. Streptococcus suis serotype 2 is one of the most important post-weaning bacterial pathogens in swine causing different infections, including pneumonia. Both pathogens are important contributors to the porcine respiratory disease complex. Outbreaks of swine influenza virus with a significant level of co-infections due to S. suis have lately been reported. In order to analyze, for the first time, the transcriptional host response of swine tracheal epithelial (NPTr) cells to H1N1 swine influenza virus (swH1N1) infection, S. suis serotype 2 infection and a dual infection, we carried out a comprehensive gene expression profiling using a microarray approach. Results: Gene clustering showed that the swH1N1 and swH1N1/S. suis infections modified the expression of genes in a similar manner. Additionally, infection of NPTr cells by S. suis alone resulted in fewer differentially expressed genes compared to mock-infected cells. However, some important genes coding for inflammatory mediators such as chemokines, interleukins, cell adhesion molecules, and eicosanoids were significantly upregulated in the presence of both pathogens compared to infection with each pathogen individually. This synergy may be the consequence, at least in part, of an increased bacterial adhesion/invasion of epithelial cells previously infected by swH1N1, as recently reported. Conclusion: Influenza virus would replicate in the respiratory epithelium and induce an inflammatory infiltrate comprised of mononuclear cells and neutrophils. In a co-infection situation, although these cells would be unable to phagocyte and kill S. suis, they are highly activated by this pathogen. S. suis is not considered a primary pulmonary pathogen, but an exacerbated production of proinflammatory mediators during a co-infection with influenza virus may be important in the pathogenesis and clinical outcome of S. suis-induced respiratory diseases.

Capsular sialic acid of Streptococcus suis serotype 2 binds to swine influenza virus and enhances bacterial interactions with virus-infected tracheal epithelial cells.

Streptococcus suis serotype 2 is an important swine bacterial pathogen, and it is also an emerging zoonotic agent. It is unknown how S. suis virulent strains, which are usually found in low quantities in pig tonsils, manage to cross the first host defense lines to initiate systemic disease. Influenza virus produces a contagious infection in pigs which is frequently complicated by bacterial coinfections, leading to significant economic impacts. In this study, the effect of a preceding swine influenza H1N1 virus (swH1N1) infection of swine tracheal epithelial cells (NTPr) on the ability of S. suis serotype 2 to adhere to, invade, and activate these cells was evaluated. Cells preinfected with swH1N1 showed bacterial adhesion and invasion levels that were increased more than 100-fold compared to those of normal cells. Inhibition studies confirmed that the capsular sialic acid moiety is responsible for the binding to virus-infected cell surfaces. Also, preincubation of S. suis with swH1N1 significantly increased bacterial adhesion to/invasion of epithelial cells, suggesting that S. suis also uses swH1N1 as a vehicle to invade epithelial cells when the two infections occur simultaneously. Influenza virus infection may facilitate the transient passage of S. suis at the respiratory tract to reach the bloodstream and cause bacteremia and septicemia. S. suis may also increase the local inflammation at the respiratory tract during influenza infection, as suggested by an exacerbated expression of proinflammatory mediators in coinfected cells. These results give new insight into the complex interactions between influenza virus and S. suis in a coinfection model.

Modelling scenarios of diffusion and control of pandemic influenza, italy

En aquest article es resumeixen els resultats publicats en un informe de l' ISS (Istituto Superiore di Sanità) del desembre de 2006, sobre un model matemàtic desenvolupat per un grup de treball que inclou a investigadors de les Universitats de Trento, Pisa i Roma, i els Instituts Nacionals de Salut (Istituto Superiore di Sanità, ISS), per avaluar i mesurar l'impacte de la transmissió i el control de la pandèmia de grip

Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium

The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary "dead end." We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.