Influenza Virus Shedding in Laninamivir-Treated Children upon Returning to School

Kondo, Hiroki; Shobugawa, Yugo; Hibino, Akinobu; Yagami, Ren; Dapat, Clyde; Okazaki, Masanori; Otsuka, Taketo; Fujii, Koyata; Hassan, Mohd Rohaizat; Saito, Reiko

doi:10.1620/tjem.238.113

Cited by 15 publications

(13 citation statements)

References 43 publications

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“…The School Health Act enacted in 1958 in Japan contains various regulations on school safety and hygiene [32]. The School Health and Safety Act in Japan states that children with influenza infection should stay home for at least 6 days after symptom onset [33]. The same act designates that the school masters can decide whether to close the class, grade, or school depending on the size of outbreaks.…”

Section: National Influenza Surveillancementioning

confidence: 99%

Japanese Surveillance Systems and Treatment for Influenza

Zaraket

Saito

2016

Curr Treat Options Infect Dis

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Opinion statementInfluenza management and surveillance programs in Japan possess several unique features. The national influenza surveillance is affiliated with National Epidemiological Surveillance for Infectious Diseases (NESID) and features sentinel outpatient surveillance, virological surveillance, and reports on hospitalization, mortality, and influenza-associated encephalopathy. Of note, information on the number of student absences and class/grade/school closures due to influenza are also reported to the government and made publically available. A private online influenza surveillance portal by volunteer doctors provides a real-time information source for the Japanese clinicians and the general public. For influenza treatment, three classes of drugs are approved and covered by national medical insurance in Japan: M2 inhibitors, neuraminidase inhibitors (NAIs), and a polymerase inhibitor. Four NAIs, oseltamivir, zanamivir, laninamivir, and peramivir, are licensed in Japan and are prescribed to seven to eight million patients annually. NAIs are prescribed to any influenza outpatient rather than being limited to severe cases. The majority (80–95 %) of patients start the treatment within 48 h of onset. Laninamivir and peramivir were used almost solely in Japan, until the approval of the latter drug by the FDA. Observational studies showed that the two drugs have equal effectiveness as oseltamivir and zanamivir. The Japanese approach to influenza surveillance and management has facilitated bringing new influenza antivirals to the markets and has driven innovative research in this field. New classes of antivirals, including polymerase inhibitors and cap-dependent endonuclease inhibitor, provide novel tools for treatment of influenza in Japan and the rest of the world.

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Section: National Influenza Surveillancementioning

confidence: 99%

Japanese Surveillance Systems and Treatment for Influenza

Zaraket

Saito

2016

Curr Treat Options Infect Dis

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“…Notably, adamantanes are not recommended for treating influenza as current strains have shown significant resistance [ 3 ]. NAIs are widely used and recommended for the treatment of influenza in high-risk patients [ 3 ]; however, these antivirals are limited in that they are most effective when administered within 48 h of symptom onset [ 4 ] and may be associated with insufficient decreases in virus titers and prolonged virus shedding [ 5 – 7 ]. The latter may result in decreased virologic and clinical benefit.…”

Section: Introductionmentioning

confidence: 99%

Safety, Tolerability, and Pharmacokinetics of the Novel Anti-influenza Agent Baloxavir Marboxil in Healthy Adults: Phase I Study Findings

et al. 2018

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Background and ObjectiveBaloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. This first-in-human phase I study evaluated the safety, tolerability, and pharmacokinetics of baloxavir marboxil/baloxavir acid in healthy Japanese volunteers (Study 1), while food effects were evaluated in a separate phase I, crossover study in healthy Japanese volunteers (Study 2).MethodsStudy 1 participants were randomized to single-dose oral baloxavir marboxil (6, 20, 40, 60, or 80 mg; n = 6 per dose) or placebo (n = 10), while Study 2 participants (n = 15) received single-dose oral baloxavir marboxil 20 mg in fasted, fed, and before-meal states.ResultsBaloxavir marboxil was well tolerated; there were few treatment-emergent adverse events and no serious adverse events/deaths. The mean plasma baloxavir acid concentration 24 h after single-dose (C24) oral baloxavir marboxil 6 mg was 6.92 ng/mL, exceeding the target C24 (6.85 ng/mL) estimated in nonclinical studies. In Study 1, baloxavir acid exposure demonstrated dose-proportional increases in the fasted state, with maximum plasma concentration generally attained within 3.5 h. Terminal elimination half-life ranged from 49 to 91 h. In Study 2, exposure was decreased and apparent clearance increased in the fed and before-meal states versus the fasted state; however, exposure exceeded the target C24 in all states.ConclusionSingle-dose oral baloxavir marboxil was well tolerated, had a favorable safety profile, and had favorable pharmacokinetic characteristics, including a long half-life, supporting single oral dosing. The baloxavir acid area under the plasma concentration-time curve decreased with food intake by approximately 40%.

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“…While the A(H7N9) viruses are resistant to M2-ion channel blockers, treatment with oseltamivir and peramivir have been reported to be effective in patients with A(H7N9) infection 5,14 , with oseltamivir the most widely used drug 15 . Importantly, evidence for the therapeutic effects of oseltamivir treatment has been accumulating; however, the available NAIs show limited ability to reduce viral titers, therefore, there may be limited virologic or therapeutic advantages, especially in patients with severe influenza with high viral loads 16–18 . In addition, the emergence of drug resistant mutants have been detected after NAI treatment against seasonal and zoonotic influenza A virus infections 19–23 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil

Taniguchi

Ando

Nobori

et al. 2019

Sci Rep

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Human infections with avian-origin influenza A(H7N9) virus represent a serious threat to global health; however, treatment options are limited. Here, we show the inhibitory effects of baloxavir acid (BXA) and its prodrug baloxavir marboxil (BXM), a first-in-class cap-dependent endonuclease inhibitor, against A(H7N9), in vitro and in vivo . In cell culture, BXA at four nanomolar concentration achieved a 1.5–2.8 log reduction in virus titers of A(H7N9), including the NA-R292K mutant virus and highly pathogenic avian influenza viruses, whereas NA inhibitors or favipiravir required approximately 20-fold or higher concentrations to achieve the same levels of reduction. A(H7N9)-specific amino acid polymorphism at position 37, implicated in BXA binding to the PA endonuclease domain, did not impact on BXA susceptibility. In mice, oral administration of BXM at 5 and 50 mg/kg twice a day for 5 days completely protected from a lethal A/Anhui/1/2013 (H7N9) challenge, and reduced virus titers more than 2–3 log in the lungs. Furthermore, the potent therapeutic effects of BXM in mice were still observed when a higher virus dose was administered or treatment was delayed up to 48 hours post infection. These findings support further investigation of BXM for A(H7N9) treatment in humans.

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Influenza Virus Shedding in Laninamivir-Treated Children upon Returning to School

Cited by 15 publications

References 43 publications

Japanese Surveillance Systems and Treatment for Influenza

Japanese Surveillance Systems and Treatment for Influenza

Safety, Tolerability, and Pharmacokinetics of the Novel Anti-influenza Agent Baloxavir Marboxil in Healthy Adults: Phase I Study Findings

Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil

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