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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#Avian #Influenza #H5N6 Viruses Exhibit Differing #Pathogenicities and #Transmissibilities in #Mammals (Sci Rep., abstract)

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

Sci Rep. 2017 Nov 24;7(1):16280. doi: 10.1038/s41598-017-16139-1.

Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and Transmissibilities in Mammals.

Zhao Z1, Guo Z1, Zhang C1, Liu L1, Chen L2, Zhang C2, Wang Z1, Fu Y1, Li J1, Shao H3, Luo Q4, Qian J5, Liu L6.

Author information: 1 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. 2 College of Veterinary Medicine, Hebei Agricultural University, 2596 lucky south street, Baoding, 071000, Hebei, China. 3 Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China. 4 Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China. qingping0523@163.com. 5 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. qianj1970@126.com. 6 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. liulinna7@126.com.

Erratum in Author Correction: Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and Transmissibilities in Mammals. [Sci Rep. 2018]

 

Abstract

Since 2013, highly pathogenic avian influenza H5N6 viruses have emerged in poultry and caused sporadic infections in humans, increasing global concerns regarding their potential as human pandemic threats. Here, we characterized the receptor-binding specificities, pathogenicities and transmissibilities of three H5N6 viruses isolated from poultry in China. The surface genes hemagglutinin (HA) and neuraminidase (NA) were closely related to the human-originating strain A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were clustered in the 2.3.4.4 clade, and the NA genes were derived from H6N6 viruses. These H5N6 viruses bound both α-2,3-linked and α-2,6-linked sialic acid receptors, but they exhibited different pathogenicities in mice. In addition, one virus was fully infective and transmissible by direct contact in guinea pigs. These results highlight the importance of monitoring the continual adaptation of H5N6 viruses in poultry due to their potential threat to human health.

PMID: 29176564 PMCID: PMC5701206 DOI: 10.1038/s41598-017-16139-1 [Indexed for MEDLINE]  Free PMC Article

Keywords: Avian Influenza; H5N6; H6N6; Reassortant strain; Poultry; Human; Animal models.

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Emergence of #human #monkeypox in west #Africa (Lancet Infect Dis., summary)

[Source: The Lancet Infectious Diseases, full page: (LINK). Summary, edited.]

Emergence of human monkeypox in west Africa

Giovanni Rezza

Published: July 05, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30281-6

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Human monkeypox is a zoonotic disease that is endemic to central and western Africa. It is caused by an orthopoxvirus that was first identified in captive monkeys in 1958, and in a child from DR Congo in 1970. There are two variants of the virus: the Congo Basin clade and the west African clade. Unlike the variola virus, the monkeypox virus has a wide range of hosts and a reservoir in wild animals. 1

(…)

Keywords: Orthopoxvirus; Monkeypox; Human; West Africa.

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#Outbreak of #human #monkeypox in #Nigeria in 2017–18: a #clinical and #epidemiological #report (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Outbreak of human monkeypox in Nigeria in 2017–18: a clinical and epidemiological report

Adesola Yinka-Ogunleye, MPH, Olusola Aruna, FFPH, Mahmood Dalhat, MBBS, Prof Dimie Ogoina, FMCP, Andrea McCollum, PhD, Yahyah Disu, MPH, Ibrahim Mamadu, MPH, Afolabi Akinpelu, BSc, Adama Ahmad, MPH, Joel Burga, BSc, Adolphe Ndoreraho, BSc, Edouard Nkunzimana, BSc, Lamin Manneh, BSc, Amina Mohammed, BSc, Olawunmi Adeoye, MBBS, Daniel Tom-Aba, MSc, Bernard Silenou, MSc, Oladipupo Ipadeola, MPH, Muhammad Saleh, MBBS, Ayodele Adeyemo, BTech, Ifeoma Nwadiutor, MBBS, Neni Aworabhi, MBBS, Patience Uke, MPH, Doris John, MBBS, Paul Wakama, MBBS, Mary Reynolds, PhD, Matthew R Mauldin, PhD, Jeffrey Doty, MS, Kimberly Wilkins, BS, Joy Musa, MSc, Asheena Khalakdina, PhD, Adebayo Adedeji, PhD, Nwando Mba, MSc, Olubunmi Ojo, MSc, Prof Gerard Krause, MD *, Chikwe Ihekweazu, FFPH * for the CDC Monkeypox Outbreak Team †

Published: July 05, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30294-4

 

Summary

Background

In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017–18 human monkeypox outbreak in Nigeria.

Methods

We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus.

Findings

122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility.

Interpretation

This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria.

Funding

None.

Keywords: Monkeypox: Human; Nigeria.

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A case of #reassortant seasonal #influenza A(#H1N2) virus, #Denmark, April 2019 (Euro Surveill., abstract)

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

A case of reassortant seasonal influenza A(H1N2) virus, Denmark, April 2019

Ramona Trebbien1, Anders Koch2, Lene Nielsen3, Dår Kristian Kur4, Pontus Westerström5, Tyra Grove Krause2

Affiliations: 1 National Influenza Center, Statens Serum Institut, Copenhagen, Denmark; 2 Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark; 3 Department of Clinical Microbiology, Herlev Hospital, Copenhagen University, Herlev, Denmark; 4 Department of Clinical Biochemistry, North Zealand Hospital, Hillerød, Denmark; 5 Department of Pulmonary and Infectious Diseases, North Zealand Hospital, Hillerød, Denmark

Correspondence:  Ramona Trebbien

Citation style for this article: Trebbien Ramona, Koch Anders, Nielsen Lene, Kur Dår Kristian, Westerström Pontus, Krause Tyra Grove. A case of reassortant seasonal influenza A(H1N2) virus, Denmark, April 2019. Euro Surveill. 2019;24(27):pii=1900406. https://doi.org/10.2807/1560-7917.ES.2019.24.27.1900406

Received: 21 Jun 2019;   Accepted: 03 Jul 2019

 

Abstract

A reassortant influenza A subtype H1N2 virus with gene segments from seasonal A(H1N1)pdm09 virus (HA, MP, NP, NS, PA, PB1 and PB2) and seasonal A(H3N2) virus (NA) was identified in a routine surveillance sample in Denmark. The patient recovered fully. This is the second reassortant influenza A(H1N2) virus identified in Europe in the 2018/19 influenza season, with the first case being detected December 2018 in Sweden.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; H1N2; Reassortant strain; Human; Denmark.

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Highly pathogenic #avian #influenza #H7N9 viruses with reduced susceptibility to #neuraminidase #inhibitors showed comparable #replication capacity to their sensitive counterparts (Virol J., abstract)

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

Virol J. 2019 Jul 2;16(1):87. doi: 10.1186/s12985-019-1194-9.

Highly pathogenic avian influenza H7N9 viruses with reduced susceptibility to neuraminidase inhibitors showed comparable replication capacity to their sensitive counterparts.

Tang J1, Zhang J1, Zhou J1, Zhu W1, Yang L1, Zou S1, Wei H1, Xin L1, Huang W1, Li X1, Cheng Y1, Wang D2.

Author information: 1 National Institute for Viral Disease Control and Prevention Chinese Centers for Disease Control and Prevention Key Laboratory for Medical Virology, National Health Commission, NO.155 Changbai road, Changping District, Beijing, 102206, People’s Republic of China. 2 National Institute for Viral Disease Control and Prevention Chinese Centers for Disease Control and Prevention Key Laboratory for Medical Virology, National Health Commission, NO.155 Changbai road, Changping District, Beijing, 102206, People’s Republic of China. dayanwang@cnic.org.cn.

 

Abstract

BACKGROUND:

Human infection with avian influenza H7N9 virus was first reported in 2013. Since the fifth epidemic, a highly pathogenic avian influenza (HPAI) H7N9 virus has emerged and caused 33 human infections. Several potential NAI resistance sites have been found in human cases. However, the drug susceptibility and replication ability of HPAI H7N9 virus with such substitutions have not yet been studied.

METHODS:

Thirty-three HPAI H7N9 virus strains were isolated from human cases in China, and then sequences were analyzed to identify potential NAI resistance sites. Recombinant influenza viruses were generated to evaluate the effect of NA amino acid substitutions on NAI (oseltamivir or zanamivir) susceptibility and viral replication efficiency in MDCK cells.

RESULTS:

Four potential NAI resistance sites, R292 K, E119V, A246T or H274Y, were screened. All four substitutions conferred either reduced or highly reduced susceptibility to oseltamivir or zanamivir. 292 K not only highly reduced the susceptibility of HPAI H7N9 to oseltamivir but also induced an increase in the IC50 of zanamivir. 119 V or 274Y conferred reduced susceptibility of HPAI H7N9 to oseltamivir. Additionally, 246 T conferred reduced susceptibility to zanamivir. All tested NAI-resistant viruses were capable of replication in MDCK cells. The virus yields of rg006-NA292K were lower than those of rg006-NA292R at 24, 48, 72 and 96 h postinfection (P<0.05). Rg006-NA119V, rg006-NA246T or rg006-NA274Y showed comparable replication capacity to wild-type virus (except for rg006-NA274Y at 96 h, P<0.05).

CONCLUSIONS:

All 4 amino acid substitutions (R292 K, E119V, A246T or H274Y) in NA reduced the susceptibility of HPAI H7N9 to NAIs. The NAI-resistant mutations in HPAI H7N9, in most cases, did not reduce the replication ability of the virus in mammalian cells. Special attention needs to be paid to these mutations, and the development of new anti-H7N9 drugs is of great importance.

KEYWORDS: Drug resistance; Highly pathogenic avian influenza H7N9; Influenza virus; Neuraminidase; Replication capacity; Reverse genetics

PMID: 31266524 DOI: 10.1186/s12985-019-1194-9

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

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