Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

Jefferson, Tom; Jones, Mark; Doshi, Peter; Mar, Chris B Del; Heneghan, Carl; Hama, Rokuro; Thompson, Matthew

doi:10.1002/14651858.cd008965.pub3

Cited by 441 publications

(295 citation statements)

References 127 publications

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“…Neuraminidase inhibitors (NAIs), primarily oseltamivir and zanamivir, were widely recommended for patients with suspected or confirmed influenza A(H1N1)pdm09 virus infection 6, 7. However, prior to the 2009–2010 pandemic, evidence of their effectiveness in seasonal influenza, while strong for modest symptom alleviation, was less robust for reductions in pneumonia incidence or improvements in pneumonia outcome 8, 9, 10. The findings from meta‐analyses have been inconsistent.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…The clinical use of the four currently available NAIs differs among countries: oral oseltamivir and inhaled zanamivir are approved for use worldwide; intravenous peramivir is approved in Japan, South Korea, and China; and inhaled laninamivir is approved in Japan (8). Although data from clinical trials suggest that oseltamivir appears less effective against influenza B viruses than influenza A viruses (9), the majority of clinical studies contain little information about influenza B viruses and did not provide statistical analysis of oseltamivir effectiveness between virus types (10).…”

mentioning

confidence: 99%

Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

Burnham

Baranovich

Marathe

et al. 2014

Antimicrob Agents Chemother

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Influenza B viruses cause annual outbreaks of respiratory illness in humans and are increasingly recognized as a major cause of influenza-associated pediatric mortality. Neuraminidase (NA) inhibitors (NAIs) are the only available therapy for patients infected with influenza B viruses, and the potential emergence of NAI-resistant viruses is a public health concern. The NA substitutions located within the enzyme active site could not only reduce NAI susceptibility of influenza B virus but also affect virus fitness. In this study, we investigated the effect of single NA substitutions on the fitness of influenza B/Yamanashi/166/1998 viruses (Yamagata lineage). We generated recombinant viruses containing either wild-type (WT) NA or NA with a substitution in the catalytic (R371K) or framework (E119A, D198E, D198Y, I222T, H274Y, and N294S) residues. We assessed NAI susceptibility, NA biochemical properties, NA protein expression, and virus replication in vitro and in differentiated normal human bronchial epithelial (NHBE) cells. Our results showed that four NA substitutions (D198E, I222T, H274Y, and N294S) conferred reduced inhibition by oseltamivir and three (E119A, D198Y, and R371K) conferred highly reduced inhibition by oseltamivir, zanamivir, and peramivir. All NA substitutions, except for D198Y and R371K, were genetically stable after seven passages in MDCK cells. Cell surface NA protein expression was significantly increased by H274Y and N294S substitutions. Viruses with the E119A, I222T, H274Y, or N294S substitution were not attenuated in replication efficiency in vitro or in NHBE cells. Overall, viruses with the E119A or H274Y NA substitution possess fitness comparable to NAI-susceptible virus, and the acquisition of these substitutions by influenza B viruses should be closely monitored.

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“…The estimates on the effectiveness of antivirals is varied, with some estimates claiming a 60 % reduction in susceptibility (Ferguson et al 2006;Longini et al 2005). However, these figures have been disputed (Jefferson et al 2012). In this work, a more conservative estimate of antiviral effectiveness is chosen, setting the reduction in susceptibility, ρ, and infectiousness, τ , to 0.3 in line with some experimental estimates (Stiver 2003;Hayden et al 2004); we also set the mean effective duration of antivirals, κ = 1, so they last one infectious period on average.…”

Section: Parametersmentioning

confidence: 99%

Choice of Antiviral Allocation Scheme for Pandemic Influenza Depends on Strain Transmissibility, Delivery Delay and Stockpile Size

et al. 2016

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Recently, pandemic response has involved the use of antivirals. These antivirals are often allocated to households dynamically throughout the pandemic with the aim being to retard the spread of infection. A drawback of this is that there is a delay until infection is confirmed and antivirals are delivered. Here an alternative allocation scheme is considered, where antivirals are instead preallocated to households at the start of a pandemic, thus reducing this delay. To compare these two schemes, a deterministic approximation to a novel stochastic household model is derived, which allows efficient computation of key quantities such as the expected epidemic final size, expected early growth rate, expected peak size and expected peak time of the epidemic. It is found that the theoretical best choice of allocation scheme depends on strain transmissibility, the delay in delivering antivirals under a dynamic allocation scheme and the stockpile size. A broad summary is that for realistic stockpile sizes, a dynamic allocation scheme is superior with the important exception of the epidemic final size under a severe pandemic scenario. Our results, viewed in conjunction with the practical considerations of implementing a preallocation scheme, support a focus on attempting to reduce the delay in delivering antivirals under a dynamic allocation scheme during a future pandemic.

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Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

Cited by 441 publications

References 127 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

Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

Choice of Antiviral Allocation Scheme for Pandemic Influenza Depends on Strain Transmissibility, Delivery Delay and Stockpile Size

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