Persistence of pandemic influenza H1N1 virus in young patients after oseltamivir therapy in the 2009–2010 season: a comparison with seasonal H1N1 with or without H275Y mutation

Kawai, Naoki; Ikematsu, Hideyuki; Iwaki, Norio; Kondou, Kunio; Hirotsu, Nobuo; Kawashima, Takashi; Maeda, Tetsunari; Tanaka, Osame; Doniwa, Kenichi; Iwakuni, Osamu; Egashira, Keisuke; Yamaji, Kouzaburo; Kashiwagi, Seizaburo

doi:10.1007/s10156-011-0314-2

Cited by 11 publications

(6 citation statements)

References 25 publications

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“…However, we did not demonstrate longer shedding duration of influenza A (H1N1)pdm09 among children compared with adults, either between or within studies. Three of the five studies in the review that directly compared shedding duration in adults to children observed shedding to be longer in children, whilst three other studies not included in the review – primarily because shedding was measured as virus titre or load – were also split in their findings: two studies found significantly longer shedding duration in children, whilst no difference was found in another . A further two studies reported no difference in the proportion of adults and children with prolonged viral shedding of more than 7 days .…”

Section: Discussionmentioning

confidence: 99%

Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age

Fielding

Kelly

Mercer

et al. 2013

Influenza Resp Viruses

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Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords ‘H1N1’, ‘pandemic’, ‘pandemics’, ‘shed’ and ‘shedding’. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.

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Section: Discussionmentioning

confidence: 99%

Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age

Fielding

Kelly

Mercer

et al. 2013

Influenza Resp Viruses

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“…In early 2015, the first imported H7N9 cases in North America were described in two travelers returning from China; both patients were given oseltamivir and eventually recovered from the disease (6). However, influenza viruses can develop resistance to oseltamivir in patients receiving prophylaxis and/or treatment, as was shown with the seasonal H1N1 and H1N1pdm09 viruses carrying H274Y (H275Y in N1 numbering; for consistency, N2 numbering is used throughout the paper) (7,8), or through spontaneous changes (9)(10)(11). Further, among oseltamivir-resistant variants, E119V, R292K, and D197N/E substitutions have been commonly detected in H3N2 and type B viruses (12)(13)(14)(15).…”

mentioning

confidence: 95%

Neuraminidase Mutations Conferring Resistance to Oseltamivir in Influenza A(H7N9) Viruses

Marjuki

Mishin

Chesnokov

et al. 2015

J Virol

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Human infections by avian influenza A(H7N9) virus entail substantial morbidity and mortality. Treatment of infected patients with the neuraminidase (NA) inhibitor oseltamivir was associated with emergence of viruses carrying NA substitutions. In the NA inhibition (NI) assay, R292K conferred highly reduced inhibition by oseltamivir, while E119V and I222K each caused reduced inhibition. To facilitate establishment of laboratory correlates of clinically relevant resistance, experiments were conducted in ferrets infected with virus carrying wild-type or variant NA genes recovered from the A/Taiwan/ 1/2013 isolate. Oseltamivir treatment (5 or 25 mg/kg of body weight/dose) was given 4 h postinfection, followed by twicedaily treatment for 5 days. Treatment of ferrets infected with wild-type virus resulted in a modest dose-dependent reduction (0.7 to 1.5 log 10 50% tissue culture infectious dose [TCID 50 ]) in nasal wash viral titers and inflammation response. Conversely, treatment failed to significantly inhibit the replication of R292K or E119V virus. A small reduction of viral titers was detected on day 5 in ferrets infected with the I222K virus. The propensity for oseltamivir resistance emergence was assessed in oseltamivir-treated animals infected with wild-type virus; emergence of R292K virus was detected in 3 of 6 ferrets within 5 to 7 days postinfection. Collectively, we demonstrate that R292K, E119V, and I222K reduced the inhibitory activity of oseltamivir, not only in the NI assay, but also in infected ferrets, judged particularly by viral loads in nasal washes, and may signal the need for alternative therapeutics. Thus, these clinical outcomes measured in the ferret model may correlate with clinically relevant oseltamivir resistance in humans. IMPORTANCEThis report provides more evidence for using the ferret model to assess the susceptibility of influenza A(H7N9) viruses to oseltamivir, the most prescribed anti-influenza virus drug. The information gained can be used to assist in the establishment of laboratory correlates of human disease and drug therapy. The rapid emergence of viruses with R292K in treated ferrets correlates well with the multiple reports on this NA variant in treated human patients. Our findings highlight the importance of the discovery and characterization of new antiviral drugs with different mechanisms of action and the use of combination treatment strategies against emerging viruses with pandemic potential, such as avian H7N9 virus, particularly against those carrying drug resistance markers.

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“…In contrast, we have previously shown that children less than 6 years of age infected with the seasonal H275Y A(H1N1) virus had delayed fever resolution compared with those infected with the sensitive virus [18]. Another Japanese group demonstrated that oseltamivir was less effective for children but it was effective for adult infected with seasonal H275Y A(H1N1) virus [19]. This discrepancy in findings could be due to differences in sample size, and between seasonal A(H1N1) or A(H1N1)pdm09 infections.…”

Section: Textmentioning

confidence: 99%

Community- and hospital-acquired infections with oseltamivir- and peramivir-resistant influenza A(H1N1)pdm09 viruses during the 2015–2016 season in Japan

Hibino

Kondo

Masaki³

et al. 2016

Virus Genes

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We report five cases of community- and hospital-acquired infections with oseltamivir- and peramivir-resistant A(H1N1)pdm09 viruses possessing the neuraminidase (NA) H275Y mutation during January–February 2016 in Japan. One case was hospitalized and was receiving oseltamivir for prophylaxis. The remaining four cases were not taking antiviral drugs at the time of sampling. These cases were geographically distant and epidemiologically unrelated. The five viruses showed ~300-fold rise in IC50 values against oseltamivir and peramivir, defined as highly reduced inhibition according to the WHO definition. Overall, the prevalence of the H275Y A(H1N1)pdm09 viruses was 1.8 % (5/282). The resistant viruses possessed the V241I, N369 K, and N386 K substitutions in the NA that have been previously reported among A(H1N1)pdm09 to alter transmission fitness. Analysis of Michaelis constant (Km) revealed that two of the isolates had reduced NA affinity to MUNANA, while the other three isolates displayed a slightly decreased affinity compared to the sensitive viruses. Further studies are needed to monitor the community spread of resistant viruses and to assess their transmissibility.Electronic supplementary materialThe online version of this article (doi:10.1007/s11262-016-1396-9) contains supplementary material, which is available to authorized users.

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Persistence of pandemic influenza H1N1 virus in young patients after oseltamivir therapy in the 2009–2010 season: a comparison with seasonal H1N1 with or without H275Y mutation

Cited by 11 publications

References 25 publications

Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age

Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age

Neuraminidase Mutations Conferring Resistance to Oseltamivir in Influenza A(H7N9) Viruses

Community- and hospital-acquired infections with oseltamivir- and peramivir-resistant influenza A(H1N1)pdm09 viruses during the 2015–2016 season in Japan

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