Duration of fever and symptoms in influenza-infected children treated with baloxavir marboxil during the 2019–2020 season in Japan and detection of influenza virus with the PA E23K substitution

Wagatsuma, Keita; Saito, Reiko; Chon, Irina; Phyu, Wint Wint; Fujio, Kakuya; Kawashima, Takashi; Sato, Ichiro; Saito, Tadashi; Minato, Michiyoshi; Kodo, Naoki; Suzuki, Eitaro; Ono, Yoko; Masaki, Hironori; Shirahige, Yutaka; Kitano, Akito; Hamabata, Hirotsune; Sun, Yuyang; Li, Jiaming; Watanabe, Hirotaka

doi:10.1016/j.antiviral.2022.105310

Cited by 10 publications

(9 citation statements)

References 30 publications

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“…In the vaccination group, over half were unvaccinated patients (54.4%, 316/581). There were no patients found to have NAI-resistant variant viruses (NA/H275Y) after oseltamivir treatment, but 21 (4.5%) patients developed baloxavir-resistant variants viruses (PA/I38T, I38M, I38K, E23K, and E119Q) in the clinical samples of influenza A (9 A/H1N1pdm09 and 12 A/H3N2) after baloxavir treatment [ 14 , 27 , 28 ]. No PA variants were detected in influenza B-infected patients.…”

Section: Resultsmentioning

confidence: 99%

“…Genetic sequencing was conducted using the Sanger method to confirm the presence of amino acid substitutions in NA and PA genes that confer resistance to baloxavir or NAIs (Additional file 1 : Methods) [ 14 , 27 , 28 ]. Genetic sequencing of NA gene was conducted on all isolates generated on MDCK or MDCK-SIAT 1 cells throughout the study period, and that of PA gene on all clinical samples collected between 2018/2019 and 2019/2020 seasons [ 14 , 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

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Factors associated with viral RNA shedding and evaluation of potential viral infectivity at returning to school in influenza outpatients after treatment with baloxavir marboxil and neuraminidase inhibitors during 2013/2014–2019/2020 seasons in Japan: an observational study

Wagatsuma

Sun

et al. 2023

BMC Infect Dis

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Background This study assessed the differences in daily virus reduction and the residual infectivity after the recommended home stay period in Japan in patients infected with influenza and treated with baloxavir (BA), laninamivir (LA), oseltamivir (OS), and zanamivir (ZA). Methods We conducted an observational study on children and adults at 13 outpatient clinics in 11 prefectures in Japan during seven influenza seasons from 2013/2014 to 2019/2020. Virus samples were collected twice from influenza rapid test-positive patients at the first and second visit 4–5 days after the start of treatment. The viral RNA shedding was quantified using quantitative RT-PCR. Neuraminidase (NA) and polymerase acidic (PA) variant viruses that reduce susceptibility to NA inhibitors and BA, respectively, were screened using RT-PCR and genetic sequencing. Daily estimated viral reduction was evaluated using univariate and multivariate analyses for the factors such as age, treatment, vaccination status, or the emergence of PA or NA variants. The potential infectivity of the viral RNA shedding at the second visit samples was determined using the Receiver Operator Curve based on the positivity of virus isolation. Results Among 518 patients, 465 (80.0%) and 116 (20.0%) were infected with influenza A (189 with BA, 58 with LA, 181 with OS, 37 with ZA) and influenza B (39 with BA, 10 with LA, 52 with OS, 15 with ZA). The emergence of 21 PA variants in influenza A was detected after BA treatment, but NA variants were not detected after NAIs treatment. Multiple linear regression analysis showed that the daily viral RNA shedding reduction in patients was slower in the two NAIs (OS and LA) than in BA, influenza B infection, aged 0–5 years, or the emergence of PA variants. The residual viral RNA shedding potentially infectious was detected in approximately 10–30% of the patients aged 6–18 years after five days of onset. Conclusions Viral clearance differed by age, type of influenza, choice of treatment, and susceptibility to BA. Additionally, the recommended homestay period in Japan seemed insufficient, but reduced viral spread to some extent since most school-age patients became non-infectious after 5 days of onset.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Factors associated with viral RNA shedding and evaluation of potential viral infectivity at returning to school in influenza outpatients after treatment with baloxavir marboxil and neuraminidase inhibitors during 2013/2014–2019/2020 seasons in Japan: an observational study

Wagatsuma

Sun

et al. 2023

BMC Infect Dis

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“…I38X (T/M/F/N) contributed to most of the variants reported, which emerged in 2.2% to 9.7% of adult and adolescent groups [59,60 ▪▪ ,66,72 ▪ ], and up to 12.5% to 23.4% of the paediatric group [61,62,63 ▪▪ ,73] during the baloxavir treatment. Another type of variant, E23K, was detected at a lower incidence (1.3% to 1.5%) [64,72 ▪ ]. Global analysis on the frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low (less than 0.5%) but it was higher in Japan (4.5%) probably due to extensive baloxavir usage [53].…”

Section: Endonuclease Inhibitormentioning

confidence: 96%

“…This was also supported by the MiniSTONE-2, which compared baloxavir with oseltamivir and showed comparable rates of adverse events and alleviation of signs and symptoms of influenza [63 && ]. A Japanese observation study in outpatient children aged less than 19 years found a marginally longer fever duration in the oseltamivir group but a similar duration of symptoms compared with the baloxavir group [64]. A retrospective cohort found that baloxavir use was associated with a lower incidence of emergency visits and better cost savings, especially in high-risk patients, compared to oseltamivir [65].…”

Section: Clinical Efficacy Of Endonuclease Inhibitormentioning

confidence: 99%

“…Inhaled laninamivir can also be an effective option for PEP in household contacts, with the advantage of a much shorter course than oseltamivir [90,91]. With an effective viral suppressive effect [64,84 ▪ ,92,93] and a low risk of adverse events, baloxavir is superior to placebo [72 ▪ ] and oseltamivir [94 ▪ ] as PEP. PEP non-compliance is a major concern, as 63.1% of healthcare workers did not complete oseltamivir PEP in a survey [95].…”

Section: Use Of Antiviral Agents To Control the Spread Of Influenza I...mentioning

confidence: 99%

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Antiviral therapies for influenza

Chan

Hui

2023

Current Opinion in Infectious Diseases

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Purpose of reviewThe heavily suppressed global influenza activity during the coronavirus disease 2019 (COVID-19) pandemic is expected to return upon relaxation of travel restriction and nonpharmaceutical interventions (NPI). We reviewed the four marketed neuraminidase inhibitors (NAI e.g., oseltamivir, zanamivir, peramivir, laninamivir) and the only endonuclease inhibitor (baloxavir) on their clinical therapeutic effects and the ability of viral suppression in various groups of patients of different clinical settings based on the latest evidence.Recent findingsEarly initiation, preferably within 48 h of symptom onsets, of antiviral treatments with NAI and baloxavir, is crucial to produce favourable outcomes in patients with influenza infection. Updated evidence does not suggest routine use of combined antiviral agents in patients with influenza infection. Treatment-emergent resistant influenza variants may occur during NAI and baloxavir use, but it has no major impact on subsequent recovery. Early treatment of index patients with influenza infection and post-exposure prophylaxis in specific populations is crucial in preventing influenza transmission.SummaryAntiviral therapy is the major defence therapeutically in the community and hospital settings to expedite early recovery and reduce influenza-related complications. Early treatment of index patients and post-exposure prophylaxis in susceptible close contacts may mitigate the spread of infection.

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Influenza A virus polymerase acidic protein E23R substitution is a marker of reduced susceptibility to baloxavir

Rovito

Penaflor

et al. 2022

Antiviral Research

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Duration of fever and symptoms in influenza-infected children treated with baloxavir marboxil during the 2019–2020 season in Japan and detection of influenza virus with the PA E23K substitution

Cited by 10 publications

References 30 publications

Factors associated with viral RNA shedding and evaluation of potential viral infectivity at returning to school in influenza outpatients after treatment with baloxavir marboxil and neuraminidase inhibitors during 2013/2014–2019/2020 seasons in Japan: an observational study

Factors associated with viral RNA shedding and evaluation of potential viral infectivity at returning to school in influenza outpatients after treatment with baloxavir marboxil and neuraminidase inhibitors during 2013/2014–2019/2020 seasons in Japan: an observational study

Antiviral therapies for influenza

Influenza A virus polymerase acidic protein E23R substitution is a marker of reduced susceptibility to baloxavir

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