Antiviral Therapy and Outcomes of Influenza Requiring Hospitalization in Ontario, Canada

McGeer, Allison; Green, Karen A.; Plevneshi, Agron; Shigayeva, Altynay; Siddiqi, Nilofar; Raboud, Janet; Low, Donald E.

doi:10.1086/523584

Cited by 363 publications

(287 citation statements)

References 32 publications

(26 reference statements)

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“…Our other findings that NAI treatment at any time versus no NAI, and later NAI treatment compared with no NAI, universally increased the risks of IRP, contrast sharply with previous observational data on hospitalised influenza patients which found that NAI treatment (irrespective of timing) and later antiviral therapy (initiated >48 hours after illness onset) may improve a range of clinical outcomes 19, 23, 24, 25, 26, 27, 28. Essentially similar observations were made for ‘any pneumonia’.…”

Section: Discussioncontrasting

confidence: 99%

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

Muthuri¹,

Venkatesan²,

Myles³

et al. 2016

Influenza Resp Viruses

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BackgroundThe impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.MethodsA worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids.ResultsOf 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)].ConclusionsEarly NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

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Section: Discussioncontrasting

confidence: 99%

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

Muthuri¹,

Venkatesan²,

Myles³

et al. 2016

Influenza Resp Viruses

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“…Even in combination with optimal supportive care, therapy with antiviral drugs does not completely prevent mortality (8), indicating that new therapeutic approaches are needed. Given reports that microthombi are observed in the lungs of patients with severe influenza (10,19) and that platelet inhibition ameliorates certain forms of lung injury (14,15), we hypothesized that the influenza virus induces platelet adhesion to the lung endothelium and that this process contributes to the pathology of severe influenza.…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic options are limited. While antiviral drugs exist, they only partially reduce mortality (8), they must be administered early to be maximally effective, and their use is complicated by the rapid development of resistance. For instance, almost 100% of H3N2 strains of influenza A are already resistant to amantadine (9).…”

mentioning

confidence: 99%

Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

Sugiyama

Gamage

Zyla

et al. 2016

J Virol

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Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin ␣ 5 ␤ 1 , implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza. Here, we show that this infection causes platelets to adhere to the lung endothelium. Importantly, blocking platelets using two distinct antiplatelet drugs improved survival in a mouse model of severe influenza infection. Thus, platelet inhibition may constitute a novel therapeutic strategy to improve the host response to severe infections with influenza.

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“…This is often difficult to achieve, as illustrated by a USA study which showed that therapy was initiated at a median of 3 days after onset of symptoms, with only 39% of hospitalised patients receiving antiviral therapy within 48 h (39). However, it has been suggested that oseltamivir therapy may still be beneficial in the treatment of seasonal influenza if initiated later (61), and may therefore be of benefit in pandemic H1N1/09 infection as well. During the current pandemic, patients who survived hospitalisation were 7.4 times (95% CI, 1.8-31) more likely to have received neuraminidase inhibitors than those who died (8).…”

Section: Antiviral Treatmentmentioning

confidence: 99%

Pandemic influenza A (H1N1) 2009: the experience of the first six months

Maritz

Maree²,

Preiser³

2009

Clinical Chemistry and Laboratory Medicine

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After a break of 41 years, 2009 saw the first influenza pandemic of the 21st century caused by a triple-reassortant influenza A (H1N1) virus. The current estimated case fatality rate is lower than that of previous influenza pandemics, but this may change as the pandemic evolves. Illness frequently occurs in previously healthy, young adults with a wide range of clinical presentations. The majority of circulating pandemic viruses remain susceptible to neuraminidase inhibitors, although all strains are intrinsically resistant to the adamantanes. Monovalent vaccines against the pandemic strain are available in both live attenuated and inactivated forms. This review aims to summarise important virological, epidemiological and clinical aspects of the pandemic influenza A (H1N1) virus for physicians and other clinical personnel. Clin Chem Lab Med 2010;48:11-21.

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Antiviral Therapy and Outcomes of Influenza Requiring Hospitalization in Ontario, Canada

Cited by 363 publications

References 32 publications

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

Pandemic influenza A (H1N1) 2009: the experience of the first six months

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