Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

Li, Qun; Zhou, Lei; Zhou, Minghao; Chen, Zhiping; Li, Furong; Wu, Huanyu; Xiang, Nijuan; Chen, Enfu; Tang, Fenyang; Wang, Dayang; Meng, Lu; Zhou, Hong; Tu, Wei; Cao, Yang; Li, Leilei; Ding, Fan; Liu, Bo; Wang, Mei; Xie, Rongheng; Gao, Rongbao; Li, Xiaodan; Bai, Tian; Zou, Shumei; He, Jun; Hu, Jiayu; Xu, Yangting; Chai, Chengliang; Wang, Shiwen; Gao, Yongjun; Jin, Lianmei; Zhang, Yanping; Luo, Heng; Yu, Hongjie; He, Jianfeng; Li, Qi; Wang, Xianjun; Gao, Lidong; Pang, Xinghuo; Li, Guohua; Yan-sheng, Yan; Yuan, Hui; Shu, Yuelong; Yang, Weizhong; Wang, Yu; Wu, Fan; Uyeki, Timothy M.; Feng, Zijian

doi:10.1056/nejmoa1304617

Cited by 623 publications

(648 citation statements)

References 53 publications

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“…The large majority of persons identified with influenza A(H7N9) virus infection presented with severe disease8 and approximately 40% died2. Persons with mild, atypical, and asymptomatic infections are far less likely to be tested for influenza A(H7N9) and will usually not seek health care.…”

Section: Introductionmentioning

confidence: 99%

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Xiang

Bai

Kang

et al. 2017

Influenza Resp Viruses

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BackgroundThe first human infections of novel avian influenza A(H7N9) virus were identified in China in March 2013. Sentinel surveillance systems and contact tracing may not identify mild and asymptomatic human infections of influenza A(H7N9) virus.ObjectivesWe assessed the seroprevalence of antibodies to influenza A(H7N9) virus in three populations during the early stages of the epidemic.Patients/MethodsFrom March 2013 to May 2014, we collected sera from the general population, poultry workers, and contacts of confirmed infections in nine Chinese provinces reporting human A(H7N9) infections and, for contacts, second sera 2‐3 weeks later. We screened for A(H7N9) antibodies by advanced hemagglutination inhibition (HI) assay and tested sera with HI titers ≥20 by modified microneutralization (MN) assay. MN titers ≥20 or fourfold increases in paired sera were considered seropositive.ResultsAmong general population sera (n=1480), none were seropositive. Among poultry worker sera (n=1866), 28 had HI titers ≥20; two (0.11%, 95% CI: 0.02‐0.44) were positive by MN. Among 61 healthcare and 117 non‐healthcare contacts’ sera, five had HI titers ≥20, and all were negative by MN. There was no seroconversion among 131 paired sera.ConclusionsThere was no evidence of widespread transmission of influenza A(H7N9) virus during March 2013 to May 2014, although A(H7N9) may have caused rare, previously unrecognized infections among poultry workers. Although the findings suggest that there were few undetected cases of influenza A(H7N9) early in the epidemic, it is important to continue monitoring transmission as virus and epidemic evolve.

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Section: Introductionmentioning

confidence: 99%

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Xiang

Bai

Kang

et al. 2017

Influenza Resp Viruses

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“…There have been four influenza pandemics within the past 100 y, including the devastating H1N1 outbreak in 1918 (6) and the H1N1 outbreak in 2009 (7). Although zoonotic avian viruses of the H5N1, H7N3, H7N7, H7N9, H9N2, and H10N8 subtypes have failed to spread in humans, fatality rates have approached 60% for some of these outbreaks (8,9). Mutations that can facilitate human transmission of these zoonotic viruses are being identified (10,11).…”

mentioning

confidence: 99%

Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor

Song

Kumar

Shadrick

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The influenza endonuclease is an essential subdomain of the viral RNA polymerase. It processes host pre-mRNAs to serve as primers for viral mRNA and is an attractive target for antiinfluenza drug discovery. Compound L-742,001 is a prototypical endonuclease inhibitor, and we found that repeated passaging of influenza virus in the presence of this drug did not lead to the development of resistant mutant strains. Reduced sensitivity to L-742,001 could only be induced by creating point mutations via a random mutagenesis strategy. These mutations mapped to the endonuclease active site where they can directly impact inhibitor binding. Engineered viruses containing the mutations showed resistance to L-742,001 both in vitro and in vivo, with only a modest reduction in fitness. Introduction of the mutations into a second virus also increased its resistance to the inhibitor. Using the isolated wild-type and mutant endonuclease domains, we used kinetics, inhibitor binding and crystallography to characterize how the two most significant mutations elicit resistance to L-742,001. These studies lay the foundation for the development of a new class of influenza therapeutics with reduced potential for the development of clinical endonuclease inhibitorresistant influenza strains.

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“…9 An epidemiological study in China between May 2013 and May 2014 showed 6.7% of case contacts developed H7N9 antibodies, suggesting that human-to-human transmission occurs and could cause mild or asymptomatic infection. 10 Both human-to-human household and hospital clusters have been described. 11,12 Transmissibility of avian influenza to humans depends on a balance of activities of the viral surface glycoproteins HA and neuraminidase (NA).…”

Section: Concern For An Avian H7n9 Influenza Pandemicmentioning

confidence: 99%

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

Moise

Biron

Boyle

et al. 2018

Human Vaccines & Immunotherapeutics

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The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4+ T cell epitopes – without perturbing native antigen structure – by galvanizing HA-specific memory helper T cells that support sustained antibody development against the native target HA. The premise for this vaccine concept rests on (i) the significance of CD4+ T cell memory to influenza immunity, (ii) the essential role CD4+ T cells play in development of neutralizing antibodies, (iii) linked specificity of HA-derived CD4+ T cell epitopes to antibody responses, (iv) the structural plasticity of HA and (v) an illustration of improved antibody response to a prototype engineered recombinant H7-HA vaccine. Immune engineering can be applied to development of vaccines against pandemic concerns, including avian influenza, as well as other difficult targets.

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Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

Abstract: Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

Cited by 623 publications

References 53 publications

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

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