#Oseltamivir #Treatment for #Children with #Influenza-Like Illness in #China: A Cost-Effectiveness Analysis (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

Open Access / Peer-reviewed / Research Article

Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis

Kunling Shen, Tengbin Xiong , Seng Chuen Tan, Jiuhong Wu

PLOS / Published: April 15, 2016 / http://dx.doi.org/10.1371/journal.pone.0153664

 

Abstract

Background

Influenza is a common viral respiratory infection that causes epidemics and pandemics in the human population. Oseltamivir is a neuraminidase inhibitor—a new class of antiviral therapy for influenza. Although its efficacy and safety have been established, there is uncertainty regarding whether influenza-like illness (ILI) in children is best managed by oseltamivir at the onset of illness, and its cost-effectiveness in children has not been studied in China.

Objective

To evaluate the cost-effectiveness of post rapid influenza diagnostic test (RIDT) treatment with oseltamivir and empiric treatment with oseltamivir comparing with no antiviral therapy against influenza for children with ILI.

Methods

We developed a decision-analytic model based on previously published evidence to simulate and evaluate 1-year potential clinical and economic outcomes associated with three managing strategies for children presenting with symptoms of influenza. Model inputs were derived from literature and expert opinion of clinical practice and research in China. Outcome measures included costs and quality-adjusted life year (QALY). All the interventions were compared with incremental cost-effectiveness ratios (ICER).

Results

In base case analysis, empiric treatment with oseltamivir consistently produced the greatest gains in QALY. When compared with no antiviral therapy, the empiric treatment with oseltamivir strategy is very cost effective with an ICER of RMB 4,438. When compared with the post RIDT treatment with oseltamivir, the empiric treatment with oseltamivir strategy is dominant. Probabilistic sensitivity analysis projected that there is a 100% probability that empiric oseltamivir treatment would be considered as a very cost-effective strategy compared to the no antiviral therapy, according to the WHO recommendations for cost-effectiveness thresholds. The same was concluded with 99% probability for empiric oseltamivir treatment being a very cost-effective strategy compared to the post RIDT treatment with oseltamivir.

Conclusion

In the Chinese setting of current health system, our modelling based simulation analysis suggests that empiric treatment with oseltamivir to be a cost-saving and very cost-effective strategy in managing children with ILI.

_____

Citation: Shen K, Xiong T, Tan SC, Wu J (2016) Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis. PLoS ONE 11(4): e0153664. doi:10.1371/journal.pone.0153664

Editor: Soren Gantt, University of British Columbia, CANADA

Received: December 1, 2015; Accepted: April 2, 2016; Published: April 15, 2016

Copyright: © 2016 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This project was sponsored by HEC Pharm, a subsidiary of HEC Group. The funder provided support in the form of salaries for authors Tengbin Xiong and Seng Chuen Tan, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.

Competing interests: Tengbin Xiong and Seng Chuen Tan are current employees of IMS Health, which received funds from HEC Pharm for this study. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. No patents have been applied for relating to the content of the manuscript. None of the authors has any other financial or nonfinancial competing interests.

Keywords: Research; Abstracts; Seasonal Influenza; Antivirals; Oseltamivir; China.

——

The #significance of naturally occurring #neuraminidase #quasispecies of #H5N1 #avian #influenza virus on #resistance to #oseltamivir: a point of concern (J Gen Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Gen Virol. 2016 Mar 2. doi: 10.1099/jgv.0.000444. [Epub ahead of print]

The significance of naturally occurring neuraminidase quasispecies of H5N1 avian influenza virus on resistance to oseltamivir: a point of concern. [      ]

Schaduangrat N1, Phanich J2, Rungrotmongkol T3, Lerdsamran H4, Puthavathana P5, Ubol S6.

Author information: 11Mahidol University. 22Chulalongkorn University. 33Chulalongkorn University. 44Mahidol University. 55Mahidol University. 66Mahidol University.

 

Abstract

Viral adaptability and survival arise due to the presence of quasispecies populations that are able to escape the immune response or produce drug-resistant variants. However, the presence of H5N1 virus with natural mutations acquired without any drug selection pressure, poses a great threat. Cloacal samples collected from the 2004-2005 epidemics in Thailand from Asian open-billed storks revealed one major and several minor quasispecies populations with mutations on the oseltamivir binding site of the neuraminidase gene (NA) without prior exposure to a drug. Therefore, this study investigated the binding between the NA containing novel mutations and oseltamivir drug (OTV) using molecular dynamic (MD) simulations and plaque inhibition assay. The results revealed that the mutant populations, S236F mutant, S236F/C278Y mutant, A250V/V266A/P271H/G285S mutant and C278Y mutant, had a lower binding affinity with OTV as compared to the wild-type virus due to rearrangement of amino acid residues and increased flexibility in the 150-loop. This result was further emphasized through the obtained IC50 values of the major population and wild-type virus, 104.74nM and 18.30nM respectively. Taken together, these data suggests that H5N1 viruses isolated from wild birds, have already acquired oseltamivir resistant point mutations without any exposure to a drug.

PMID: 26935590 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; H5N1; Avian Influenza; Antivirals; Drugs Resistance; Wild Birds.

——

#Efficacy of #oseltamivir #peramivir combination #therapy compared to oseltamivir monotherapy for #Influenza A (#H7N9) #infection: a retrospective study (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2016 Feb 10;16(1):76. doi: 10.1186/s12879-016-1383-8.

Efficacy of oseltamivir-peramivir combination therapy compared to oseltamivir monotherapy for Influenza A (H7N9) infection: a retrospective study. [      ]

Zhang Y1, Gao H2, Liang W3, Tang L4, Yang Y5, Wu X6, Yu L7, Chen P8, Zheng S9, Ou H10, Li L11.

Author information: 1The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. doctorzy02@163.com. 2The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. gaohainv@163.com. 3The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. dr.liangwf@163.com. 4The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. lltang72@163.com. 5The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. yidayang@hotmail.com. 6The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. 21318023@zju.edu.cn. 7The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. yuliangzju@163.com. 8The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. chenping362@163.com. 9The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. zsfzhzheng@163.com. 10The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. ouhuilin@163.com. 11The State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, HangZhou, China. ljli@zju.edu.cn.

 

Abstract

BACKGROUND:

Since the novel H7N9 avian influenza outbreak occurred in China in 2013, neuraminidase inhibitors (NAIs) such as oseltamivir and peramivir have been used as first-line drugs to treat the influenza virus infection. This study aimed to compare the efficacy of oseltamivir-peramivir combination therapy versus oseltamivir monotherapy.

METHODS:

A retrospective study of 82 H7N9 confirmed patients was conducted by reviewing medical charts at the First Affiliated Hospital of ZheJiang University in China from April 1, 2013 to Feb 28, 2014. The patients’ clinical information was collected systematically, and we compared the virology and clinical data between oseltamivir monotherapy group (43 patients) and oseltamivir-peramivir combination group (39 patients).

RESULTS:

The median duration from NAIs administration to H7N9 virus-negative in oseltamivir monotherapy group and oseltamivir-peramivir combination group was 6.50 and 7.00 days (p >0.05), respectively. The median decline of Day 2 to Day 0 (initiation of NAIs therapy) viral load was 0.00 and 0.69 log10 copies/μl (p >0.05) respectively in the monotherapy vs. combination therapy groups. The incidence of new Acute Respiratory Distress Syndrome during NAI administration was 63.89 and 77.78 % (p >0.05); while the mortality rates were 25.58 and 43.59 % (p >0.05) in the oseltamivir group vs. oseltamivir-peramivir group.

CONCLUSIONS:

Our results suggest that in adults with H7N9 virus infection, the use of oseltamivir-peramivir combination therapy was not superior to oseltamivir monotherapy.

PMID: 26864456 [PubMed – in process]

Keywords: Research; Abstracts; Oseltamivir; Peramivir; Antivirals; Avian Influenza; H7N9; Human.

——

Emergence of #influenza #H1N1pdm09 genogroup 6B and #drug #resistant #virus, #India, January to May 2015 (@eurosurveillanc, abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Eurosurveillance, Volume 21, Issue 5, 04 February 2016 / Rapid communication

Emergence of influenza A(H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015 [      ]

M Parida 1 , PK Dash 1, JS Kumar 1, G Joshi 1, K Tandel 1, S Sharma 1, A Srivastava 1, A Agarwal 1, A Saha 1, S Saraswat 1, D Karothia 1, V Malviya 1

Author affiliations: 1. Division of Virology, Defence Research & Development Establishment (DRDE), Gwalior, India

Correspondence: Manmohan Parida ( paridamm@rediffmail.com)

Citation style for this article: Parida M, Dash P, Kumar J, Joshi G, Tandel K, Sharma S, Srivastava A, Agarwal A, Saha A, Saraswat S, Karothia D, Malviya V. Emergence of influenza A(H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015. Euro Surveill. 2016;21(5):pii=30124. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.5.30124

Received:11 December 2015; Accepted:04 February 2016

 

Abstract

To investigate the aetiology of the 2015 A(H1N1)pdm09 influenza outbreak in India, 1,083 nasopharyngeal swabs from suspect patients were screened for influenza A(H1N1)pdm09 in the state of Madhya Pradesh. Of 412 positive specimens, six were further characterised by phylogenetic analysis of haemagglutinin (HA) sequences revealing that they belonged to genogroup 6B. A new mutation (E164G) was observed in HA2 of two sequences. Neuraminidase genes in two of 12 isolates from fatal cases on prior oseltamivir treatment harboured the H275Y mutation.

Keywords: Research; Abstracts; Seasonal Influenza; H1N1pdm09; Antivirals; Drugs Resistance; Oseltamivir; India.

——-

#Drug #Repurposing Identifies #Inhibitors of #Oseltamivir-Resistant #Influenza #Viruses (Angew Chem Int Ed Engl., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Angew Chem Int Ed Engl. 2016 Feb 2. doi: 10.1002/anie.201511361. [Epub ahead of print]

Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses. [      ]

Bao J1, Marathe B2, Govorkova EA2, Zheng JJ3,4,5.

Author information: 1Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA. 2Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA. 3Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA. jzheng@jsei.ucla.edu. 4Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. jzheng@jsei.ucla.edu. 5Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA. jzheng@jsei.ucla.edu.

 

Abstract

The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti-influenza drug. However, oseltamivir-resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir-resistant, alternative therapy options are needed. Herein, we show that a structure-based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir-resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild-type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir-resistance mutation itself caused susceptibility to these drugs.

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS: computational chemistry; drug discovery; drug repurposing; influenza viruses; neuraminidase

PMID: 26833677 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Influenza A; Antivirals; Drugs Resistance; Oseltamivir.

——

#Influenza #viruses received and tested by the #Melbourne #WHO CC for Reference and Research on Influenza annual report, 2014 (Commun Dis Intell Q Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Commun Dis Intell Q Rep. 2015 Dec 31;39(4):E602-E611.

Influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza annual report, 2014. [      ]

Sullivan SG 1, Chow MK 1, Barr IG 1, Kelso A 1.

Author information: 1Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.

 

Abstract

The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne is part of the World Health Organization’s (WHO) Global Influenza Surveillance and Response System. In 2014 the Centre received a total of 5,374 influenza samples from laboratories primarily in the Asia-Pacific region. Viruses were characterised by their antigenic, genetic and antiviral drug resistance properties. Of the viruses successfully analysed 52% were A(H1N1)pdm09 viruses. The majority of these were antigenically and genetically similar to the WHO recommended reference strain for the 2014 Southern Hemisphere influenza vaccine. Results for A(H3N2) and B/Yamagata viruses suggested that circulating viruses of this subtype and lineage, respectively, had undergone antigenic and/or genetic changes, consistent with the decision by WHO to change recommended strains for the 2015 Southern Hemisphere vaccine. A small number of A(H1N1)pdm09 and B/Victoria viruses had highly reduced inhibition to the neuraminidase inhibitors oseltamivir and zanamivir. The Centre also undertook primary isolation of vaccine candidate viruses directly into eggs. A total of 38 viruses were successfully isolated in eggs, of which 1 (B/Phuket/3073/2013) was included in the 2015 Southern Hemisphere influenza vaccine.

PMID: 26779736 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Seasonal Influenza; H1N1pdm09; H3N2; Influenza B; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir.

——-

#Virus #Susceptibility and #Clinical #Effectiveness of #Antiinfluenza #Drugs During the 2010-2011 #Influenza Season in #Russia (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2016 Jan 8. pii: S1201-9712(16)00002-3. doi: 10.1016/j.ijid.2016.01.001. [Epub ahead of print]

Virus Susceptibility and Clinical Effectiveness of Anti-influenza Drugs During the 2010-2011 Influenza Season in Russia. [      ]

Leneva IA 1, Burtseva EI 2, Yatsyshina SB 3, Fedyakina IT 2, Kirillova ES 2, Selkova EP 4, Osipova E 5, Maleev VV 3.

Author information: 1I Mechnikov Research Institute of Vaccines and Sera of Russian Academy of Science, Moscow, Russia. Electronic address: wnyfd385@yandex.ru. 2D I. Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Moscow, Russia. 3Central Research Institute for Epidemiology, Rospotrebhadzor of the Russian Federation, Moscow, Russia. 4Gabrichevsky Moscow Research Institute for Epidemiology and Microbiology Rospotrebhadzor Moscow, Russia. 5I Mechnikov Research Institute of Vaccines and Sera of Russian Academy of Science, Moscow, Russia.

 

Abstract

Antiviral drugs are critical adjuncts to influenza vaccination. Here we determined in vitro susceptibility of influenza A and B viruses isolated in 2010-2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir. We assessed antiviral potency of these drugs against A(H1N1)pdm09 virus in mice. Importantly, we evaluated clinical effectiveness of oseltamivir and umifenovir in a retrospective study conducted in 26 regions of Russia. All tested viruses (n=36) were susceptible to oseltamivir and umifenovir in vitro. Oseltamivir (10mg/kg/day) and umifenovir (60mg/kg/day) significantly increased (p<0.05) survival of mice challenged with A/California/04/2009 (H1N1)pdm09 virus. Influenza infection was laboratory-confirmed in 442 patients among 1,462 hospitalized patients with acute respiratory infection. Treatment of influenza-infected patients within 48hours of symptoms onset with oseltamivir and umifenovir was associated with a significant (p<0.001) decrease in the duration of illness (2-3 days) and symptoms. Pneumonia was observed in none and 0.3% patients treated with oseltamivir and umifenovir, respectively, compared to 23.7% patients without antiviral therapy (p<0.001). This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which continue to circulate in post-pandemic seasons.

Copyright © 2016. Published by Elsevier Ltd.

KEYWORDS: influenza; observational study; oseltamivir; susceptibility to antivirals; umifenovir

PMID: 26775570 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Seasonal Influenza; Russia; H1N1pdm09; Antivirals; Oseltamivir; Umifenovir.

——