#EIDs: Focus on #infection #control #issues for novel #coronaviruses (#SARS-CoV & #MERS-CoV), #VHF (#Lassa and #Ebola), and HPAI viruses, #H5N1 & #H7N9 (SD, abstract)

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

American Journal of Infection Control / Volume 44, Issue 5, Supplement, 2 May 2016, Pages e91–e100  / Disinfection, Sterilization and Antisepsis: Principles, Practices, Current Issues, New Research and New Technologies / Major article

Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9)

David J. Weber, MD, MPHa, b,  William A. Rutala, PhD, MPHa, b, William A. Fischer, MDc, Hajime Kanamori, MD, PhD, MPHa, b, Emily E. Sickbert-Bennett, PhD, MSa, b

a Department of Hospital Epidemiology, University of North Carolina Health Care, Chapel Hill, NC; b Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC; c Division of Pulmonary and Critical Care Medicine, University of North Carolina School of Medicine, Chapel Hill, NC

Available online 28 April 2016 / doi:10.1016/j.ajic.2015.11.018

 

Abstract

Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility.

Key Words: Emerging infectious diseases; health care–associated infections; infection control; occupational health; severe acute respiratory disease; Middle East respiratory syndrome; Lassa fever; Ebola viral disease; novel influenza viruses

Funding/support: Supported by the University of North Carolina at Chapel Hill (U54CK000164).

Publication of this article was supported by an educational grant from Clorox Healthcare, Sealed Air, and Tru-D. Content of this article was initiated and written by the authors with no input or financial support to the authors from Clorox Healthcare, Sealed Air, or Tru-D.

Conflicts of Interest: None to report.

Address correspondence to David J. Weber, MD, MPH, 2163 Bioinformatics, CB #7030, Chapel Hill, NC 27599-7030. (D.J. Weber).

© 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Keywords: Research; Abstracts; Lassa Fever; Ebola; H7N9; H5N1; Avian Influenza; MERS-CoV; SARS-CoV.

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#Hemagglutinin #aminoacids related to #receptor specificity could affect the #protection efficacy of #H5N1 and #H7N9 avian #influenza virus #vaccines in mice (Vaccine, abstract)

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

Vaccine. 2016 Apr 12. pii: S0264-410X(16)30004-4. doi: 10.1016/j.vaccine.2016.03.031. [Epub ahead of print]

Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice.

Xu L1, Bao L1, Lau SY2, Wu WL2, Yuan J1, Gu S1, Li F1, Lv Q1, Xu Y1, Pushko P3, Chen H2, Qin C4.

Author information: 1Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China. 2State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Centre of Infection and Immunology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China. 3Medigen, 8420 Gas House Pike Suite S, Frederick, MD 21701, USA. 4Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China. Electronic address: qinchuan@cnilas.org.

 

Abstract

The continuous and sporadic human transmission of highly pathogenic avian H5N1 and H7N9 influenza viruses illustrates the urgent need for efficacious vaccines. However, all tested vaccines for the H5N1 and H7N9 viruses appear to be poorly immunogenic in mammals. In this study, a series of vaccines was produced using reverse genetic techniques that possess HA and NA genes from the H5N1 virus in the genetic background of the high-yield strain A/PR/8/34 (H1N1). Meanwhile, a group of H7N9 VLP vaccines that contain HA from H7N9 and NA and M1 from A/PR/8/34 (H1N1) was also produced. The HA amino acids of both the H5N1 and H7N9 vaccines differed at residues 226 and 228, both of which are critical for receptor specificity for an avian or mammalian host. Mice received two doses (3μg of HA each) of each vaccine and were challenged with lethal doses of wild type H5N1 or H7N9 viruses. The results showed that a recombinant H5N1 vaccine in which the HA amino acid G228 (avian specificity) was converted to S228 (mammalian specificity) resulted in higher HI titers, a lower viral titer in the lungs, and 100% protection in mice. However, a H7N9 VLP vaccine that contains L226 (mammalian specificity) and G228 (avian specificity) in HA showed better immunogenicity and protection efficacy in mice than VLP containing HA with either L226+S228 or Q226+S228. This observation indicated that specific HA residues could enhance a vaccine’s protection efficacy and HA glycoproteins with both avian-type and human-type receptor specificities may produce better pandemic influenza vaccines for humans.

Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS: Animal model; Influenza; Receptor specificity; Reverse genetics; Vaccine

PMID: 27083426 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; H5N1; H7N9; Avian Influenza; Vaccines.

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#Adaptive #aminoacid #substitutions enhance the #virulence of a novel #human #H7N9 #influenza #virus in mice (Vet Microbiol., abstract)

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

Vet Microbiol. 2016 May 1;187:8-14. doi: 10.1016/j.vetmic.2016.02.027. Epub 2016 Mar 3.

Adaptive amino acid substitutions enhance the virulence of a novel human H7N9 influenza virus in mice.

Zhao Y1, Yu Z2, Liu L1, Wang T1, Sun W1, Wang C1, Xia Z1, Gao Y3, Zhou B1, Qian J4, Xia X5.

Author information: 1Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People’s Republic of China. 2Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People’s Republic of China; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People’s Republic of China. 3Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People’s Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People’s Republic of China. 4Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People’s Republic of China. Electronic address: qianj1970@126.com. 5Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People’s Republic of China; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People’s Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People’s Republic of China; Beijing Institute of Biotechnology, Beijing 100071, People’s Republic of China. Electronic address: xiaxzh@cae.cn.

 

Abstract

To identify molecular features that confer enhanced H7N9 virulence in mammals, we independently generated three mouse-adapted variants of A/Shanghai/2/2013 (H7N9) by serial passage in mice. The mouse lethal doses (MLD50) of the mouse-adapted variants were reduced >1000-100000-fold when compared to the parental virus. Adapted variants displayed enhanced replication kinetics in vivo, and were capable of replicating in multiple organs. Analysis of adapted viral genomes revealed a total of 14 amino acid changes among the three variant viruses in the PA (T97I, K328R, P332T, and Q556R), HA (H3 numbering; A107T, R220I, L226Q, and R354K), NP (A284T and M352I), NA (M26I, N142S, and G389D), and M1 (M128R) proteins. Notably, many of these adaptive amino acid changes have been identified in naturally occurring H7 isolates. Our results identify amino acid substitutions that collectively enhance the ability of a human H7N9 virus to replicate and cause severe disease in mice.

Copyright © 2016 Elsevier B.V. All rights reserved.

KEYWORDS: Amino acid substitutions; H7N9 influenza virus; Mouse model; Virulence

PMID: 27066703 [PubMed – in process]

Keywords: Research; Abstracts; H7N9; Avian Influenza.

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Multiple Natural #Substitutions in #Avian #Influenza A Virus PB2 Facilitate Efficient #Replication in #Human #Cells (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Multiple Natural Substitutions in Avian Influenza A Virus PB2 Facilitate Efficient Replication in Human Cells

Benjamin Mänz a, Miranda de Graaf a, Ramona Mögling a, Mathilde Richard a, Theo M. Bestebroer a, Guus F. Rimmelzwaan a and Ron A. M. Fouchier a#

Author Affiliations: a) Department of Viroscience, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands

 

ABSTRACT

A strong restriction of the avian influenza A virus polymerase in mammalian cells generally limits viral host-range switching. Although substitutions like E627K in the PB2 polymerase subunit can facilitate polymerase activity to allow replication in mammals, many human H5N1 and H7N9 viruses lack this adaptive substitution. Here, several previously unknown, naturally occurring, adaptive substitutions in PB2 were identified by bioinformatics, and their enhancing activity verified using in vitro assays. Adaptive substitutions enhanced polymerase activity and virus replication in mammalian cells for avian H5N1 and H7N9 viruses, but not for a partially human-adapted H5N1 virus. Adaptive substitutions towards basic amino acids were frequent and were mostly clustered in a putative RNA exit channel in a polymerase crystal structure. Phylogenetic analysis demonstrated divergent dependency of influenza viruses on adaptive substitutions. The novel adaptive substitutions found in this study increase basic understanding of influenza virus host adaptation and will help in surveillance efforts.

 

IMPORTANCE

Influenza viruses from birds jump the species barrier into humans relatively frequently. Such influenza virus zoonoses may pose public health risks if the virus adapts to humans and becomes a pandemic threat. Relatively few amino acid substitutions – most notably in the receptor binding site of hemagglutinin and at positions 591 and 627 in the polymerase protein PB2 – have been identified in pandemic influenza strains as determinants of host adaptation, to facilitate efficient virus replication and transmission in humans. Here, we show that substantial numbers of amino acid substitutions are functionally compensating for the lack of the above-mentioned mutations in PB2, and could facilitate influenza virus emergence in humans.

 

FOOTNOTES

#Address correspondence to Ron A. M. Fouchier, r.fouchier@erasmusmc.nl

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; Avian Influenza; H5N1; H7N9.

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Dynamic #Quantification of #Avian #Influenza #H7N9(A) Virus in a #Human #Infection during Clinical Treatment Using Droplet Digital PCR (J Virol Methods, abstract)

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

Dynamic Quantification of Avian Influenza H7N9(A) Virus in a Human Infection during Clinical Treatment Using Droplet Digital PCR.

J Virol Methods. 2016 Apr 4;

Authors: Yan Y, Jia XJ, Wang HH, Fu XF, Ji JM, He PY, Chen LX, Luo JY, Chen ZW

 

Abstract

This study involved a human infection with avian influenza H7N9(A) virus in Zhejiang province, the first one after implementing the closure measures of living poultry markets in China. The clinical symptoms, epidemiological and virological characteristics of the case were described briefly, and as the emphasis, H7N9 virus was detected quantitatively and continuously from the collected samples in 10 different periods of the patient’s treatment in order to reveal changes of viral load in patient’s body during the treatment. This study first used reverse-transcription droplet digital PCR (RT-ddPCR) assays to monitor viral load dynamically for human H7N9 infection, synchronously performing real-time RT-PCR as a reference technology to obtain more comprehensive data for comparison. Our results indicated that RT-ddPCR compared to real-time RT-PCR is more sensitive and accurate for quantifying H7N9 viral load without the use of standard curves. Furthermore it can provide reference data for clinical policies including infectivity judgement, ward transferring and therapy adjustment for the patient during treatment.

PMID: 27058642 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Avian Influenza; H7N9; Human.

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#Emergency #surveillance for novel #influenza #H7N9 #virus in domestic #poultry, feral #pigeons and other wild birds in #Bhutan (Rev Sci Tech., abstract)

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

Rev Sci Tech. 2015 Dec;34(3):829-36.

Emergency surveillance for novel influenza A(H7N9) virus in domestic poultry, feral pigeons and other wild birds in Bhutan.

Tenzin T, Tenzin S, Tshering D, Lhamo K, Rai PB, Dahal N, Dukpa K.

 

Abstract

Following the March 2013 outbreak of novel avian influenza A(H7N9) virus in humans and the subsequent isolation of the virus from chickens, ducks and pigeons in the People’s Republic of China, concerns were raised that the H7N9 virus would spread beyond China through the poultry value chain linking to a number of bordering countries. For this reason, a rapid emergency surveillance exercise took place in Bhutan between May and July 2013 with the objective of determining whether influenza A(H7N9) virus was silently circulating in domestic poultryandwild birds in Bhutan.Atotal of 1716 oropharyngeal,tracheal and cloacal swabs together with faecal droppings were collected from poultry, wild birds and feral pigeons throughout the country; these samples included 150 that had been previously collected for surveillance of influenza A(H5N1) virus. Overall, 733 of the samples were tested. A QIAamp Viral RNA Mini K it was used to extract viral RNA from a mix of oropharyngeal, tracheal and cloacal swabs and faecal droppings. The matrix gene of avian influenza type A virus was detected using a specific real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay, and positive samples were further tested in RT-PCR for simultaneous detection of the H7 and N9 genes. Among the 733 samples tested, 46 (26 prospective, 20 retrospective) were confirmed positive for influenza A, a prevalence of 6.3% (95% CI: 4.6 to 8.3). The influenza A-positive samples were from areas in the south of Bhutan that had experienced previous outbreaks of highly pathogenic influenza A(H5N1). None of the samples tested positive for H7N9 strains, providing evidence that influenza A(H7N9) virus was not present in the sampled population. A risk-based approach for surveillance of influenza A(H7N9) and H5N1 is recommended in Bhutan, based on the epidemiology of the disease in China and other countries in South and Southeast Asia.

PMID: 27044154 [PubMed – in process]

Keywords: Research; Abstracts; Avian Influenza; Poultry; Wild Birds; Nepal; H7N9.

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Two #outbreak #sources of #influenza #H7N9 #viruses have been established in #China (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Two outbreak sources of influenza A (H7N9) viruses have been established in China

Dayan Wang, Lei Yang, Wenfei Zhu, Ye Zhang, Shumei Zou, Hong Bo, Rongbao Gao, Jie Dong, Weijuan Huang, Junfeng Guo, Zi Li, Xiang Zhao, Xiaodan Li, Li Xin, Jianfang Zhou, Tao Chen, Libo Dong, Hejiang Wei, Xiyan Li, Liqi Liu, Jing Tang, Yu Lan, Jing Yang  and Yuelong Shu*

Author Affiliations: National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention; Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, P.R. China

 

ABSTRACT

Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well-recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry, and supervision of poultry movements should be strengthened.

 

IMPORTANCE

Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have being demonstrated the continuing pandemic threat posed by the current influenza ecosystem in China. As their silently circulated in poultry while severe outcome in human, the H7N9 activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta Region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and responsible for the H7N9 outbreaks in mainland China.

 

FOOTNOTES

*Corresponding author:

Yuelong Shu, National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention; Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing 102206, P.R. China Tel, +86-10-58900850; Email: yshu@cnic.org.cn;

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; H7N9; Avian Influenza; Human; Poultry; China.

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