Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia

A potentially fatal complication of influenza infection is the development of pneumonia, caused either directly by the influenza virus, or by secondary bacterial infection. Pneumonia related to the 2009 influenza A pandemic was found to be underestimated by commonly used pneumonia severity scores in many cases, and to be rapidly progressive, leading to respiratory failure. Confirmation of etiology by laboratory testing is warranted in such cases. Rapid antigen and immunofluorescence testing are useful screening tests, but have limited sensitivity. Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral culture. The most effective preventive measure is annual influenza vaccination in selected individuals. Decisions to administer antiviral medications for influenza treatment or chemoprophylaxis should be based upon clinical and epidemiological factors, and should not be delayed by confirmatory laboratory testing results. Neuraminidase inhibitors (NI) are the agents of choice

Systematic review of influenza resistance to the neuraminidase inhibitors

<p>Abstract</p> <p>Background</p> <p>Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu^®) and zanamivir (Relenza^®); and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review.</p> <p>The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms.</p> <p>Results</p> <p>We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%). The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral resistance among subjects given peramivir and was reported to be 0%. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. A meta-analysis of 4 studies reporting association between oseltamivir-resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Oseltamivir-resistance was not statistically significantly associated with other clinical complications and symptoms.</p> <p>Conclusion</p> <p>Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance may be significantly associated with pneumonia. In contrast, zanamivir resistance has been rarely reported to date.</p

Estimating Business And Management Journal Quality From The 2008 Research Assessment Exercise In The UK

The 2008 Research Assessment Exercise in the UK involved the peer review of over 12,500 research outputs in Business and Management, of which 92% were journal articles. Each output was graded on a 4-point scale from "world leading" to "national" with a fifth point being unclassified. These grades were accumulated for each department to provide an overall quality profile in terms of the proportions of its outputs in each category. The assessments of individual papers were not made public but the papers submitted by each department were. This data provides a major opportunity for addressing issues of concern about the evaluation of research and the effects of journal rankings, as well as the possibility of reconstructing the judgements made by the Panel about journal quality. Given the submission details and the resulting grade profile for each department, we have used linear programming to produce the best estimate of the grades awarded to papers from each journal that had more than three entries. This provides both a grade profile for each journal and a single quality estimate. The results are shown to have good validity in comparison with other journal rankings. Apart from providing a ranking of 700 journals based on the RAE results, the paper is also able to shed light on issues such as the accuracy and coverage of the ABS ranking: the degree of selectivity of submissions; the dispersion of grades for a journal; and differences between different subject areas

Immunogenicity of the inactivated influenza vaccine in children who have undergone autologous stem cell transplant

CORRESPONDENCE To the Editor: Autologous stem cell transplant (SCT) is an upfront therapeutic modality for children with malignancies such as high-risk neuroblastoma and atypical teratoid rhabdoid tumour and a salvage option for children with lymphoma and a variety of solid tumours. The administration of highdose myeloablative chemotherapy during conditioning increases vulnerability to infection. Influenza infection can result in significant complications, in particular progression to pneumonia, in patients who have undergone autologous SCT [1, 2]. Influenza vaccination is recommended to prevent infection in children following autologous SCT [3], however, there is limited evidence regarding its benefit in this population [4]. Due to the paucity of data, we performed a prospective multicentre study to evaluate the immunogenicity of the seasonal inactivated influenza vaccine in children who have undergone autologous SCT compared with healthy matched controls

Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF(∆mye), LysM.Cre(+/−)TF(flox/flox)) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI