Characterization of viral #genomic #mutations in novel #influenza A (#H7N9)-infected #patients: the association between #oseltamivir-resistant variants and viral shedding duration (Virus Genes., abstract)

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

Virus Genes. 2019 Jul 13. doi: 10.1007/s11262-019-01678-8. [Epub ahead of print]

Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration.

Chen R1, Zou Q2,3, Xie G2,3, Yu F2,3, Yang X2,3, Cao L1, Huo Z4, Zheng S5,6.

Author information: 1 Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China. 2 Center of Clinical Laboratory, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China. 3 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China. 4 Experimental Teaching Center, School of Basic Medical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China. zxhuo@zju.edu.cn. 5 Center of Clinical Laboratory, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China. zsfzheng@zju.edu.cn. 6 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China. zsfzheng@zju.edu.cn.

 

Abstract

Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6, P = 0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5, P = 0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients.

KEYWORDS: Influenza A (H7N9); Mutation; Neuraminidase (NA); Oseltamivir resistance; Viral duration

PMID: 31302878 DOI: 10.1007/s11262-019-01678-8

Keywords: Avian Influenza; H7N9; Antivirals; Drugs Resistance; Oseltamivir; China; Human.

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Emergence of #Influenza A(#H7N4) Virus, #Cambodia (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Research Letter

Emergence of Influenza A(H7N4) Virus, Cambodia

Dhanasekaran Vijaykrishna, Yi-Mo Deng, Miguel L. Grau, Matthew Kay, Annika Suttie, Paul F. Horwood, Wantanee Kalpravidh, Filip Claes, Kristina Osbjer, Phillipe Dussart, Ian G. Barr, and Erik A. Karlsson

Author affiliations: Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia (D. Vijaykrishna, Y.-M. Deng, M. Kay, I.G. Barr); Monash University, Melbourne (D. Vijaykrishna, M.L. Grau); Institut Pasteur du Cambodge, Phnom Penh, Cambodia (A. Suttie, P.F. Horwood, P. Dussart, E.A. Karlsson); James Cook University, Townsville, Queensland, Australia (P.F. Horwood); Food and Agriculture Organization of the United Nations, Bangkok, Thailand (W. Kalpravidh, F. Claes); Food and Agriculture Organization of the United Nations, Phnom Penh, Cambodia (K. Osbjer)

 

Abstract

Active surveillance in high-risk sites in Cambodia has identified multiple low-pathogenicity influenza A(H7) viruses, mainly in ducks. None fall within the A/Anhui/1/2013(H7N9) lineage; however, some A(H7) viruses from 2018 show temporal and phylogenetic similarity to the H7N4 virus that caused a nonfatal infection in Jiangsu Province, China, in December 2017.

Keywords: Avian Influenza; H7N4; Reassortant strain; Cambodia.

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A #MDR #Plasmid pIMP26, Carrying blaIMP-26, fosA5, blaDHA-1, and qnrB4 in #Enterobacter cloacae (Sci Rep., abstract)

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

Article | OPEN | Published: 15 July 2019

A Multidrug Resistance Plasmid pIMP26, Carrying blaIMP-26, fosA5, blaDHA-1, and qnrB4 in Enterobacter cloacae

Su Wang,  Kaixin Zhou, Shuzhen Xiao, Lianyan Xie, Feifei Gu, Xinxin Li, Yuxing Ni, Jingyong Sun & Lizhong Han

Scientific Reports, volume 9, Article number: 10212 (2019)

 

Abstract

IMP-26 was a rare IMP variant with more carbapenem-hydrolyzing activities, which was increasingly reported now in China. This study characterized a transferable multidrug resistance plasmid harboring blaIMP-26 from one Enterobacter cloacae bloodstream isolate in Shanghai and investigated the genetic environment of resistance genes. The isolate was subjected to antimicrobial susceptibility testing and multilocus sequence typing using broth microdilution method, Etest and PCR. The plasmid was analyzed through conjugation experiments, S1-nuclease pulsed-field gel electrophoresis and hybridization. Whole genome sequencing and sequence analysis was conducted for further investigation of the plasmid. E. cloacae RJ702, belonging to ST528 and carrying blaIMP-26, blaDHA-1, qnrB4 and fosA5, was resistant to almost all β-lactams, but susceptible to quinolones and tigecycline. The transconjugant inherited the multidrug resistance. The resistance genes were located on a 329,420-bp IncHI2 conjugative plasmid pIMP26 (ST1 subtype), which contained trhK/trhV, tra, parA and stbA family operon. The blaIMP-26 was arranged following intI1. The blaDHA-1 and qnrB4cluster was the downstream of ISCR1, same as that in p505108-MDR. The fosA5 cassette was mediated by IS4. This was the first report on complete nucleotide of a blaIMP-26-carrying plasmid in E. cloacae in China. Plasmid pIMP26 hosted high phylogenetic mosaicism, transferability and plasticity.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; Enterobacter cloacae; Shanghai; China; Quinolones; Tigecycline.

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#Genomic characterizations of #H4 subtype #avian #influenza viruses from live #poultry #markets in #Sichuan province of #China, 2014-2015 (Sci China Life Sci., abstract)

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

Sci China Life Sci. 2018 Sep;61(9):1123-1126. doi: 10.1007/s11427-018-9327-4. Epub 2018 Jul 9.

Genomic characterizations of H4 subtype avian influenza viruses from live poultry markets in Sichuan province of China, 2014-2015.

Quan C1, Huang T2, Chen X2, Zhang J1, Wang Q3, Zhang C4, Zhang T5, Zhou L2, Shu L1, Long C5, Yang L6, Du X6, Zhao Y1, Liu P1, Song H7, Shi W8, Bi Y4, Lv Q2, Liu WJ9, Gao GF10,11,12.

Author information: 1 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. 2 Sichuan Center for Disease Control and Prevention, Chengdu, 610041, China. 3 School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China. 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing, 100101, China. 5 Longquanyi Center for Disease Control and Prevention, Chengdu, 610000, China. 6 Chengdu Center for Disease Control and Prevention, Chengdu, 610041, China. 7 Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China. 8 Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Taian, 271000, China. 9 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. liujun@ivdc.chinacdc.cn. 10 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. gaof@im.ac.cn. 11 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing, 100101, China. gaof@im.ac.cn. 12 Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China. gaof@im.ac.cn.

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Summary

Dear Editor, Avian influenza viruses (AIVs) have posed a serious threat to poultry production and public health. To date, more than fourteen AIV subtypes that are able to infect human beings have been documented. Also, it is suggested that new subtypes may be reported in the future, owing to the migration of wild birds and live poultry transportation (Gao, 2018). Poultry may act as a potential incubator for novel subtypes of avian influenza virus (Bi et al., 2016a; Bi et al., 2016b; Liu et al., 2014a; Su et al., 2017). Up to date, the H7N9 AIV emerged in February 2013 has caused 1,567 human cases, with a fatality rate of 39.2% (http://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_02_03_2018.pdf?ua=1). Genetic analysis has demonstrated that the N9 gene derived from migratory birds, the H7 gene from ducks, and the internal genes from H9N2 virus in chickens reassorted to generate the novel H7N9 virus (Liu et al., 2014a; Liu et al., 2014b; Su et al., 2015). Notably, the majority of human infections with H7N9 AIV had a prior exposure history to live poultry markets (LPMs) (Quan et al., 2018; Tang and Wang, 2017; Xiao et al., 2017).

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PMID: 29995198 DOI: 10.1007/s11427-018-9327-4 [Indexed for MEDLINE]

Keywords: Avian Influenza; H4; Poultry; Sichuan; China; Live poultry markets.

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A novel #H7N3 #reassortant originating from the zoonotic #H7N9 highly pathogenic #avian #influenza viruses that has adapted to #ducks (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Jul 11. doi: 10.1111/tbed.13291. [Epub ahead of print]

A novel H7N3 reassortant originating from the zoonotic H7N9 highly pathogenic avian influenza viruses that has adapted to ducks.

Nakayama M1, Uchida Y1, Shibata A2, Kobayashi Y3, Mine J1, Takemae N1, Tsunekuni R1, Tanikawa T1, Harada R2, Osaka H2, Saito T1,4.

Author information: 1 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan. 2 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Tokoname, Aichi, 479-0881, Japan. 3 Pathological and Physiochemical Examination Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Yokohama, Kanagawa, 235-0008, Japan. 4 United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.

 

Abstract

The first human case of zoonotic H7N9 avian influenza virus (AIV) infection was reported in March 2013 in China. This virus continues to circulate in poultry in China while mutating to highly pathogenic AIVs (HPAIVs). Through monitoring at airports in Japan, a novel H7N3 reassortant of the zoonotic H7N9 HPAIVs, A/duck/Japan/AQ-HE30-1/2018 (HE30-1), was detected in a poultry meat product illegally brought by a passenger from China into Japan. We analyzed the genetic, pathogenic, and antigenic characteristics of HE30-1 by comparing it with previous zoonotic H7N9 AIVs and their reassortants. Phylogenetic analysis of the entire HE30-1 genomic sequence revealed that it comprised at least three different sources; the HA (H7), PB1, PA, NP, M, and NS segments of HE30-1 were directly derived from H7N9 AIVs, whereas the NA (N3) and PB2 segments of HE30-1 were unrelated to zoonotic H7N9. Experimental infection revealed that HE30-1 was lethal in chickens but not in domestic or mallard ducks. HE30-1 was shed from and replicated in domestic and mallard ducks and chickens, whereas previous zoonotic H7N9 AIVs have not adapted well to ducks. This finding suggests the possibility that HE30-1 may disseminate to remote area by wild bird migration once it establishes in wild bird population. A hemagglutination-inhibition assay indicated that antigenic drift has occurred among the reassortants of zoonotic H7N9 AIVs; HE30-1 showed similar antigenicity to some of those H7N9 AIVs, suggesting it might be prevented by the H5/H7 inactivated vaccine that was introduced in China in 2017. Our study reports the emergence of a new reassortant of zoonotic H7N9 AIVs with novel viral characteristics and warns of the challenge we still face to control the zoonotic H7N9 AIVs and their reassortants.

This article is protected by copyright. All rights reserved.

KEYWORDS: adaptation to ducks; animal experiments; novel H7N3 reassortant; zoonotic H7N9 avian influenza viruses

PMID: 31293102 DOI: 10.1111/tbed.13291

Keywords: Avian Influenza; H7N3; H7N9; Reassortant strain; Animal models.

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A Novel #Antigenic #Drift of #Avian #Influenza A(#H7N9) Virus in #Poultry, #China, 2018 (J Infect Dis., abstract)

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

A Novel Antigenic Drift of Avian Influenza A(H7N9) Virus in Poultry, China, 2018

Weixin Jia, Xiaohui Wen, Shumin Xie, Yixue Dai, Zhixian Li, Xiao Wang, Jingkai Hu, Xuanjiang Jin, Xiao Li, Wenbao Qi, Abani K Pradhan, Ming Liao

The Journal of Infectious Diseases, jiz190, https://doi.org/10.1093/infdis/jiz190

Published: 08 July 2019

Issue Section: Correspondence

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TO THE EDITOR — In their recent article, Ning et al [1] analyzed antigenic drift of influenza A(H7N9) virus haemagglutinin (HA). Their findings showed that some key mutations affecting antigenicity may have appeared in H7N9 in the past 5 years. To further evaluate the changes of antigenicity of H7N9, we studied the antigenicity and molecular characteristics of a new H7N9 virus isolated from poultry. We found a novel antigenic drift, which is different from previous findings. To our knowledge, this is the first antigenic change found after the implementation of China’s immunization policy in poultry.

After the emergence of the highly pathogenic H7N9 subtype influenza…

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Avian Influenza; H7N9; Vaccines; Poultry.

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#Clinical #analysis of seven cases of #H1N1 #influenza-associated #encephalopathy in #children (Zhonghua Er Ke Za Zhi, abstract)

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

Zhonghua Er Ke Za Zhi. 2019 Jul 2;57(7):538-542. doi: 10.3760/cma.j.issn.0578-1310.2019.07.009.

[Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children].

[Article in Chinese; Abstract available in Chinese from the publisher]

Li XF1, Ai B2, Ye JW1, He DM1, Tan LM1, Chen MX1, Yang HM1, Zeng FS1, Yang FX1, Liu HS2, Xu Y1.

Author information: 1 Department of Infectious Diseases, Guangzhou Women and Children’s Medical Center, Guangzhou 540120, China. 2 Department of Radiology, Guangzhou Women and Children’s Medical Center, Guangzhou 540120, China.

Abstract in English, Chinese

Objective:

To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children.

Methods:

The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children’s Medical Center from December 2018 to January 2019 were retrospectively analyzed.

Results:

Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge.

Conclusions:

The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

KEYWORDS: Child; Encephalopathy, influenza; Influenza A virus, H1N1 subtype

PMID: 31269554 DOI: 10.3760/cma.j.issn.0578-1310.2019.07.009

Keywords: Seasonal Influenza; H1N1pdm09; Encephalopathy; Pediatrics; Neurology; Guangdong; China.

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