Sequential Influenza B Viral Load and Susceptibility in Children Treated With Oseltamivir and Zanamivir

Sato, Masatoki; Honzumi, Ken; Sato, Toshiko; Hashimoto, Koichi; Watanabe, Masahiro; Miyazaki, Kyohei; Kawasaki, Yukihiko

doi:10.1097/inf.0000000000000266

Cited by 9 publications

(11 citation statements)

References 32 publications

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“…Khanna et al reported a decrease of >2 log 10 copies/mL in RSV load in 11 (58%) of 19 adult patients with hematologic malignancies within 7 days of initiating treatment [63]. Several case reports and case series have described the role of oseltamivir in decreasing viral load in respiratory secretions [40, 64, 65]. The significant reduction in viral load for both influenza virus and RSV seen in our study agrees with these studies.…”

Section: Discussionsupporting

confidence: 90%

Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR

et al. 2019

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Acute respiratory tract infections are a major cause of respiratory morbidity and mortality in pediatric patients worldwide. However, accurate viral and immunologic markers to predict clinical outcomes of this patient population are still lacking. Droplet digital PCR assays for influenza and respiratory syncytial virus (RSV) were designed and performed in 64 respiratory samples from 23 patients with influenza virus infection and 73 samples from 19 patients with RSV infection. Samples of patients with hematologic malignancies, solid tumors, or sickle cell disease were included. Clinical information from institutional medical records was reviewed to assess disease severity. Samples from patients with fever or respiratory symptoms had a significantly higher viral loads than those from asymptomatic patients. Samples from patients with influenza virus and RSV infection collected at presentation had significantly higher viral loads than those collected from patients after completing a course of oseltamivir or ribavirin, respectively. RSV loads correlated positively with clinical symptoms in patients ≤5 years of age, whereas influenza viral loads were associated with clinical symptoms, irrespective of age. Patients receiving antivirals for influenza and RSV had a significant reduction in viral loads after completing therapy. Digital PCR offers an effective method to monitor the efficacy of antiviral treatment for respiratory tract infections in immunocompromised hosts.

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Section: Discussionsupporting

confidence: 90%

Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR

et al. 2019

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“…As such, even with a comprehensive, well-sampled, viral titer time course, it might not be possible to resolve antiviral efficacy in a given patient as it would be indistinguishable from natural infection resolution. Studies where decay phase of the viral load are used to examine the efficacy of NAIs2829303132 are tacitly assuming that all their patients can be described with the same infection parameters, particularly that they would have the same natural decay rate in the absence of antivirals. This is not a reasonable assumption, and our study shows that even small variations in underlying dynamical parameters will alter the measured viral decay rate.…”

Section: Discussionmentioning

confidence: 99%

“…It is somewhat easier to collect information about the viral titer decay phase which occurs either after the viral titer has peaked or after highly effective treatment sufficient to abrogate the infection is applied. Indeed, several studies have relied on viral measurements starting near or after the viral titer peak to assess the efficacy of NAIs in patients2829303132.…”

mentioning

confidence: 99%

The in vivo efficacy of neuraminidase inhibitors cannot be determined from the decay rates of influenza viral titers observed in treated patients

Palmer

Dobrovolny

Beauchemin

2017

Sci Rep

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Antiviral therapy is a first line of defence against new influenza strains. Current pandemic preparations involve stock- piling oseltamivir, an oral neuraminidase inhibitor (NAI), so rapidly determining the effectiveness of NAIs against new viral strains is vital for deciding how to use the stockpile. Previous studies have shown that it is possible to extract the drug efficacy of antivirals from the viral decay rate of chronic infections. In the present work, we use a nonlinear mathematical model representing the course of an influenza infection to explore the possibility of extracting NAI drug efficacy using only the observed viral titer decay rates seen in patients. We first show that the effect of a time-varying antiviral concentration can be accurately approximated by a constant efficacy. We derive a relationship relating the true treatment dose and time elapsed between doses to the constant drug dose required to approximate the time- varying dose. Unfortunately, even with the simplification of a constant drug efficacy, we show that the viral decay rate depends not just on drug efficacy, but also on several viral infection parameters, such as infection and production rate, so that it is not possible to extract drug efficacy from viral decay rate alone.

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“…Viruses were isolated from the samples stored at Ϫ80°C for subsequent NA inhibition assays, as described previously (15). In brief, 100 l of nasal aspiration samples was inoculated on MDCK cells in a 12-well plate, and the cells were washed after a 1-h incubation at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…The PCR mix consisted of final concentrations of 1ϫ Premix Ex Taq (TaKaRa Bio Inc.), 900 nM each primer, 100 nM the probe, and 2 l of target cDNA, and the final volume was eventually made 20 l with nuclease-free water. cDNA was amplified in 40 two-step cycles (5 s at 95°C for denaturation and 31 s at 60°C for annealing and extension) using an ABI-7300 instrument (Life Technologies Corp., Carlsbad, CA, USA) (15). Virus copy numbers were determined via comparison with a serially diluted plasmid standard with a known concentration.…”

Section: Methodsmentioning

confidence: 99%

Influenza Viral Load and Peramivir Kinetics after Single Administration and Proposal of Regimens for Peramivir Administration against Resistant Variants

Sato

Ito

Suzuki

et al. 2015

Antimicrob Agents Chemother

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fWe estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (C max ) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage.

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Sequential Influenza B Viral Load and Susceptibility in Children Treated With Oseltamivir and Zanamivir

Abstract: NAI treatment was effective for inhibiting viral replication during the early days of illness and did not decrease viral susceptibility to NAIs in patients with influenza B virus infection.

Cited by 9 publications

References 32 publications

Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR

Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR

The in vivo efficacy of neuraminidase inhibitors cannot be determined from the decay rates of influenza viral titers observed in treated patients

Influenza Viral Load and Peramivir Kinetics after Single Administration and Proposal of Regimens for Peramivir Administration against Resistant Variants

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