The #evolution and #genetic #diversity of #avian #influenza A(#H9N2) viruses in #Cambodia, 2015 – 2016 (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 – 2016

Annika Suttie, Songha Tok, Sokhoun Yann, Ponnarath Keo, Srey Viseth Horm, Merryn Roe, Matthew Kaye, San Sorn, Davun Holl, Sothyra Tum, Ian G. Barr, Aeron C. Hurt, Andrew R. Greenhill,  [ … ], Paul F. Horwood

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Published: December 9, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225428

 

Abstract

Low pathogenic A(H9N2) subtype avian influenza viruses (AIVs) were originally detected in Cambodian poultry in 2013, and now circulate endemically. We sequenced and characterised 64 A(H9N2) AIVs detected in Cambodian poultry (chickens and ducks) from January 2015 to May 2016. All A(H9) viruses collected in 2015 and 2016 belonged to a new BJ/94-like h9-4.2.5 sub-lineage that emerged in the region during or after 2013, and was distinct to previously detected Cambodian viruses. Overall, there was a reduction of genetic diversity of H9N2 since 2013, however two genotypes were detected in circulation, P and V, with extensive reassortment between the viruses. Phylogenetic analysis showed a close relationship between A(H9N2) AIVs detected in Cambodian and Vietnamese poultry, highlighting cross-border trade/movement of live, domestic poultry between the countries. Wild birds may also play a role in A(H9N2) transmission in the region. Some genes of the Cambodian isolates frequently clustered with zoonotic A(H7N9), A(H9N2) and A(H10N8) viruses, suggesting a common ecology. Molecular analysis showed 100% of viruses contained the hemagglutinin (HA) Q226L substitution, which favours mammalian receptor type binding. All viruses were susceptible to the neuraminidase inhibitor antivirals; however, 41% contained the matrix (M2) S31N substitution associated with resistance to adamantanes. Overall, Cambodian A(H9N2) viruses possessed factors known to increase zoonotic potential, and therefore their evolution should be continually monitored.

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Citation: Suttie A, Tok S, Yann S, Keo P, Horm SV, Roe M, et al. (2019) The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 – 2016. PLoS ONE 14(12): e0225428. https://doi.org/10.1371/journal.pone.0225428

Editor: Charles J. Russell, St. Jude Children’s Research Hospital, UNITED STATES

Received: August 28, 2019; Accepted: November 4, 2019; Published: December 9, 2019

Copyright: © 2019 Suttie 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 manuscript and its Supporting Information files.

Funding: This publication is the result of work conducted under a cooperative agreement with the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (HHS), grant number IDSEP140020-01-00 (PH). The study was also funded, in part, by the US Agency for International Development (grant No. AID-442-G-14-00005) (PH). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health (IB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Avian Influenza; H9N2; H7N9; H9N2; H10N8; Reassortant strain; Cambodia; Antivirals; Drugs Resistance; Amantadine; Oseltamivir; Zanamivir.

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#Diversity of A(#H5N1) clade 2.3.2.1c #avian #influenza viruses with evidence of #reassortment in #Cambodia, 2014-2016 (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Diversity of A(H5N1) clade 2.3.2.1c avian influenza viruses with evidence of reassortment in Cambodia, 2014-2016

Annika Suttie,  Songha Tok, Sokhoun Yann, Ponnarath Keo, Srey Viseth Horm, Merryn Roe, Matthew Kaye, San Sorn, Davun Holl, Sothyra Tum, Philippe Buchy, Ian Barr, Aeron Hurt,  [ … ], Paul F. Horwood

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Published: December 9, 2019 / DOI: https://doi.org/10.1371/journal.pone.0226108

 

Abstract

In Cambodia, highly pathogenic avian influenza A(H5N1) subtype viruses circulate endemically causing poultry outbreaks and zoonotic human cases. To investigate the genomic diversity and development of endemicity of the predominantly circulating clade 2.3.2.1c A(H5N1) viruses, we characterised 68 AIVs detected in poultry, the environment and from a single human A(H5N1) case from January 2014 to December 2016. Full genomes were generated for 42 A(H5N1) viruses. Phylogenetic analysis shows that five clade 2.3.2.1c genotypes, designated KH1 to KH5, were circulating in Cambodia during this period. The genotypes arose through multiple reassortment events with the neuraminidase (NA) and internal genes belonging to H5N1 clade 2.3.2.1a, clade 2.3.2.1b or A(H9N2) lineages. Phylogenies suggest that the Cambodian AIVs were derived from viruses circulating between Cambodian and Vietnamese poultry. Molecular analyses show that these viruses contained the hemagglutinin (HA) gene substitutions D94N, S133A, S155N, T156A, T188I and K189R known to increase binding to the human-type α2,6-linked sialic acid receptors. Two A(H5N1) viruses displayed the M2 gene S31N or A30T substitutions indicative of adamantane resistance, however, susceptibility testing towards neuraminidase inhibitors (oseltamivir, zanamivir, lananmivir and peramivir) of a subset of thirty clade 2.3.2.1c viruses showed susceptibility to all four drugs. This study shows that A(H5N1) viruses continue to reassort with other A(H5N1) and A(H9N2) viruses that are endemic in the region, highlighting the risk of introduction and emergence of novel A(H5N1) genotypes in Cambodia.

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Citation: Suttie A, Tok S, Yann S, Keo P, Horm SV, Roe M, et al. (2019) Diversity of A(H5N1) clade 2.3.2.1c avian influenza viruses with evidence of reassortment in Cambodia, 2014-2016. PLoS ONE 14(12): e0226108. https://doi.org/10.1371/journal.pone.0226108

Editor: Charles J. Russell, St. Jude Children’s Research Hospital, UNITED STATES

Received: August 7, 2019; Accepted: November 18, 2019; Published: December 9, 2019

Copyright: © 2019 Suttie 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 manuscript and its Supporting Information files.

Funding: This publication is the result of work conducted under a cooperative agreement with the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (HHS), grant number IDSEP140020-01-00. Its contents and conclusions are solely the responsibility of the authors and do not represent the official views of HHS. The study was also funded, in part, by the US Agency for International Development (grant No. AID-442-G-14-00005) and partially funded through the UK Research and Innovation Global Challenges Research Fund to The Consortium of Animal Market Networks to Assess Risk of Emerging Infectious Diseases Through Enhanced Surveillance (CANARIES; grant No. GCRFNGR3\1497). Annika Suttie is funded by an Australian Government Research Training Program Scholarship and a Faculty of Science and Technology Research Scholarship from Federation University. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. GlaxoSmithKline Biologicals SA provided support in the form of salary for an author [PB], 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 role of this author is articulated in the ‘author contributions’ section. The authors are solely responsible for final content and interpretation.

Competing interests: GlaxoSmithKline Biologicals SA provided support in the form of salary for an author [PB]. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Keywords: Avian Influenza; H5N1; H9N2; Reassortant strains; Poultry; Human; Antivirals; Drugs Resistance; Amantadine; Oseltamivir; Zanamivir; Cambodia.

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#Influenza A virus #hemagglutinin #mutations associated with use of #NAIs correlate with decreased inhibition by anti-influenza #antibodies (Virol J., abstract)

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

Virol J. 2019 Nov 29;16(1):149. doi: 10.1186/s12985-019-1258-x.

Influenza A virus hemagglutinin mutations associated with use of neuraminidase inhibitors correlate with decreased inhibition by anti-influenza antibodies.

Ilyushina NA1, Komatsu TE2, Ince WL2, Donaldson EF2, Lee N3, O’Rear JJ2, Donnelly RP3.

Author information: 1 Division of Biotechnology Review and Research II, Food and Drug Administration CDER, WO Bldg. 52/72, Room 2105, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. natalia.ilyushina@fda.hhs.gov. 2 Division of Antiviral Products, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. 3 Division of Biotechnology Review and Research II, Food and Drug Administration CDER, WO Bldg. 52/72, Room 2105, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.

 

Abstract

BACKGROUND:

Vaccination and the use of neuraminidase inhibitors (NAIs) are currently the front lines of defense against seasonal influenza. The activity of influenza vaccines and antivirals drugs such as the NAIs can be affected by mutations in the influenza hemagglutinin (HA) protein. Numerous HA substitutions have been identified in nonclinical NAI resistance-selection experiments as well as in clinical specimens from NAI treatment or surveillance studies. These mutations are listed in the prescribing information (package inserts) for FDA-approved NAIs, including oseltamivir, zanamivir, and peramivir.

METHODS:

NAI treatment-emergent H1 HA mutations were mapped onto the H1N1 HA1 trimeric crystal structure and most of them localized to the HA antigenic sites predicted to be important for anti-influenza immunity. Recombinant A/California/04/09 (H1N1)-like viruses carrying HA V152I, G155E, S162 N, S183P, and D222G mutations were generated. We then evaluated the impact of these mutations on the immune reactivity and replication potential of the recombinant viruses in a human respiratory epithelial cell line, Calu- 3.

RESULTS:

We found that the G155E and D222G mutations significantly increased viral titers ~ 13-fold compared to the wild-type virus. The hemagglutination and microneutralization activity of goat and ferret antisera, monoclonal antibodies, and human serum samples raised against pandemic A(H1N1)pdm09 viruses was ~ 100-fold lower against mutants carrying G155E or D222G compared to the wild-type virus.

CONCLUSIONS:

Although the mechanism by which HA mutations emerge during NAI treatment is uncertain, some NAI treatment-emergent HA mutations correlate with decreased immunity to influenza virus.

KEYWORDS: Antiviral resistance; Hemagglutinin (HA); Influenza A virus; Neuraminidase (NA); Neuraminidase inhibitors (NAI)

PMID: 31783761 DOI: 10.1186/s12985-019-1258-x

Keywords: Influenza A; Antivirals; H1N1pdm09; Oseltamivir; Zanamivir; Peramivir.

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#Outcomes and #Adverse Effects With #Peramivir for the #Treatment of #Influenza #H1N1 in Critically Ill #Pediatric Patients (J Pediatr Pharmacol Ther., abstract)

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

J Pediatr Pharmacol Ther. 2019 Nov-Dec;24(6):497-503. doi: 10.5863/1551-6776-24.6.497.

Outcomes and Adverse Effects With Peramivir for the Treatment of Influenza H1N1 in Critically Ill Pediatric Patients.

Witcher R, Tracy J, Santos L, Chopra A.

 

Abstract

OBJECTIVES:

Influenza is an environmental pathogen and infection presents as a range from asymptomatic to fulminant illness. Though treatment is supportive, antiviral agents have a role in the management of infection. Pediatric use of peramivir is largely based on reports and extrapolations of pharmacokinetic data. We seek to describe efficacy and safety of peramivir in critically ill pediatric patients.

METHODS:

This is a retrospective, institutional review board-approved chart review of all patients under 21 years of age, admitted to the PICU, and treated with peramivir for influenza H1N1 infection between January 1, 2016, and March 31, 2016, at a single-center, 12-bed PICU. The primary outcome was time to sustained resolution of fever; secondary outcomes included dose, duration, and adverse effects of peramivir therapy.

RESULTS:

Seven patients were included with median age of 3.7 years. Median time to sustained resolution of fever was 49.3 hours, median duration of mechanical ventilation was 14.2 days, median ICU LOS was 18.7 days, and hospital LOS was 24.7 days. No patients suffered mortality. Three patients experienced leukopenia, one of which experienced a concurrent neutropenia. Three patients experienced hyperglycemia, 2 experienced hypertension, 1 experienced increased aspartate aminotransferase and increased alanine aminotransferase, and 1 experienced diarrhea. All adverse events assessed were classified as possible using published adverse event causality assessments.

CONCLUSIONS:

Peramivir has been shown to be an effective therapy for the treatment of influenza H1N1 in critically ill pediatric patients. In our experience with 7 pediatric patients, peramivir was well tolerated at typical durations of therapy; however, increased vigilance is warranted during prolonged courses or in patients with reasons for altered pharmacokinetics and pharmacodynamics.

Copyright Published by the Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2019.

KEYWORDS: adverse drug events; critical care; influenza; pediatric; safety

PMID: 31719811 PMCID: PMC6836703 DOI: 10.5863/1551-6776-24.6.497

Keywords: Seasonal Influenza; H1N1; Antivirals; Drugs safety; Peramivir; Pediatrics.

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#Key #aminoacid residues of #neuraminidase involved in #influenza A virus #entry (Pathog Dis., abstract)

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

Pathog Dis. 2019 Nov 8. pii: ftz063. doi: 10.1093/femspd/ftz063. [Epub ahead of print]

Key amino acid residues of neuraminidase involved in influenza A virus entry.

Chen F1, Liu T1, Xu J1, Huang Y1, Liu S1, Yang J1.

Author information: 1 Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.

 

Abstract

Generally, influenza virus neuraminidase (NA) plays a critical role in the release stage of influenza virus. Recently, it has been found that NA may promote influenza virus to access the target cells. However, the mechanism remain unclear. Here, we reported that peramivir indeed possessed anti-influenza A virus (IAV) activity in the stage of viral entry. Importantly, we verified the critical residues of influenza NA involved in the viral entry. As a result, peramivir as an efficient NA inhibitor could suppress the initiation of IAV infection. Furthermore, mutational analysis showed NA might be associated with viral entry via amino acids residues R118, E119, D151, R152, W178, I222, E227, E276, R292 and R371. Our results demonstrated neuraminidase must contain the key amino acid residues can involve in IAV entry.

© FEMS 2019.

KEYWORDS: Influenza A virus; neuraminidase; neuraminidase active site; peramivir; viral entry

PMID: 31702775 DOI: 10.1093/femspd/ftz063

Keywords: Influenza A; Peramivir; Antivirals; Viral pathogenesis.

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#Effectiveness of four types of #neuraminidase #inhibitors approved in #Japan for the #treatment of #influenza (PLoS One, abstract)

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

PLoS One. 2019 Nov 7;14(11):e0224683. doi: 10.1371/journal.pone.0224683. eCollection 2019.

Effectiveness of four types of neuraminidase inhibitors approved in Japan for the treatment of influenza.

Mawatari M1, Saito R1, Hibino A1, Kondo H1, Yagami R1, Odagiri T1,2, Tanabe I1, Shobugawa Y1; Japanese Influenza Collaborative Study Group.

Author information: 1 Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. 2 Division of Infectious Diseases and Immunology, Department of Microbiology, School of Medicine, Iwate Medical University, Iwate, Japan.

 

Abstract

BACKGROUND:

Neuraminidase inhibitors (NAIs) effectively treat influenza. The clinical effectiveness of four NAIs (oseltamivir, zanamivir, laninamivir, and peramivir) was evaluated against influenza A/H1N1pdm09, A/H3N2, and B viruses. Additionally, fever duration in patients infected with oseltamivir-resistant influenza A/H1N1pdm09 with the H275Y mutation was evaluated.

METHODS:

Patients aged <20 years who visited outpatient clinics in Japan with influenza-like illnesses were enrolled during 4 influenza seasons from 2012/2013 to 2015/2016. After obtaining informed consent, patients who tested positive for influenza with rapid tests received one of the four NAIs. Patients recorded their body temperature daily for 8 days from the first visit. The influenza strain was identified using real-time polymerase chain reaction. Univariate and multivariable analyses were used to evaluate factors influencing fever duration. In children aged ≤5 years treated with oseltamivir, fever duration in oseltamivir-resistant A/H1N1pdm09-infected patients was compared to that in oseltamivir-sensitive A/H1N1pdm09-infected patients.

RESULTS:

Of the 1,368 patients analyzed, 297 (21.7%), 683 (49.9%), and 388 (28.4%) were infected with influenza A/H1N1pdm09, A/H3N2, and B, respectively. In multivariable analysis factors associated with significantly prolonged fever duration included: treatment with laninamivir (hazard ratio [HR]: 0.78, p = 0.006, compared to oseltamivir), influenza B (HR: 0.58, p<0.001, compared to influenza A/H1N1pdm09), and a higher body temperature at the clinic visit (HR: 0.87 per degree Celsius, p<0.001). Increasing age was associated with a significantly shorter duration of fever (HR: 1.31 for 6-9 years old, p<0.001; and HR: 1.65 for 10-19 years old, p<0.001, respectively, compared to 0-5 years old). Following treatment with oseltamivir, fever duration was significantly longer for oseltamivir-resistant A/H1N1pdm09-infected patients (n = 5) than for oseltamivir-sensitive A/H1N1pdm09 infected patients (n = 111) (mean, 89 versus 40 hours, p<0.001).

CONCLUSIONS:

Our results revealed characteristic information on the effectiveness of the four NAIs and also on oseltamivir-resistant viruses that may affect patients’ clinical care.

PMID: 31697721 DOI: 10.1371/journal.pone.0224683

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Japan.

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#Adult #influenza A (#H3N2) with reduced susceptibility to #baloxavir or #peramivir cured after switching anti-influenza agents (IDCases, abstract)

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

IDCases. 2019 Oct 1;18:e00650. doi: 10.1016/j.idcr.2019.e00650. eCollection 2019.

Adult influenza A (H3N2) with reduced susceptibility to baloxavir or peramivir cured after switching anti-influenza agents.

Seki M1, Sakai-Tagawa Y2, Yasuhara A2, Watanabe Y3.

Author information: 1 Division of Infectious Diseases and Infection Control, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan. 2 Department of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 3 Laboratory for Clinical Microbiology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan.

 

Abstract

We describe two adults with A/H3N2 influenza with (patient 1), and without (patient 2) polymerase acidic (PA) subunit I38 T substitution during the same season. Patient 1 had a reduced clinical response to baloxavir, a cap-dependent endonuclease inhibitor (CEI), but was cured by peramivir, a neuraminidase inhibitor. Baloxavir was clinically effective for patient 2, for whom peramivir had been ineffective. Susceptibility to baloxavir can be decreased by a PA unit mutation, but response to treatment can be increased by switching and/or combination with a neuraminidase inhibitor, even though CEI are clinically effective against influenza in adults.

© 2019 The Authors.

KEYWORDS: Baloxavir; Peramivir; Polymerase; Polymerase acidic subunit; Viral infection

PMID: 31692637 PMCID: PMC6804930 DOI: 10.1016/j.idcr.2019.e00650

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; H3N2; Japan; Baloxavir; Peramivir.

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