Avian-Origin Influenza A(H7N9) Infection in Influenza A(H7N9)–Affected Areas of China: A Serological Study

Yang, Shigui; Chen, Yu; Cui, Dawei; Yao, Hang‐Ping; Lou, Jianzhou; Huo, Zhaoxia; Xie, Guoliang; Yu, Fei; Zheng, Shufa; Yang, Yida; Zhu, Yixin; Lü, Xiaoqing; Liu, Xiaoli; Lau, Siu-Ying; Chan, Jasper Fuk‐Woo; To, Kelvin Kai-Wang; Yuen, Kwok‐Yung; Chen, Honglin; Li, Lanjuan

doi:10.1093/infdis/jit430

Cited by 97 publications

(80 citation statements)

References 14 publications

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“…In the general population sample from two provinces examined in this study, we found no indication of infection, consistent with the findings of studies conducted in Zhejiang Province11 and Shenzhen, Guangdong province13 in 2013. Our study also found that among close contacts of infected patients, although several had an elevated HI titer, MN confirmation showed no evidence of infection; this is consistent with the results of a serologic study conducted in Guangdong in July 2013, which included close contacts12.…”

Section: Discussionsupporting

confidence: 92%

“…Although we identified two seropositive cases in poultry workers, the overall seropositivity in this study was much lower than that reported in previous serologic studies conducted in a similar time period11, 13, 14. Compared with studies that did not perform MN testing, the proportion of elevated HI titers in our study (0.1% poultry workers with HI titer ≥20) was also much lower.…”

Section: Discussioncontrasting

confidence: 86%

“…Serologic studies are needed to identify subclinical influenza A(H7N9) human infections and better describe the full spectrum of influenza A(H7N9) human infection. Although several serologic studies of influenza A(H7N9) have been published, they have been limited to single provinces11, 12, 13, 14 and have used either less sensitive serologic assays11 or lacked confirmation by microneutralization testing11, 13, 14, which improves specificity of serologic testing results15.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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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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“…Live poultry in wet markets are an important source of human infection, since most of the patients have evidence of exposure to poultry (9,10). This is further supported by seroepidemiological data suggesting that more than 6% of exposed poultry workers are seropositive for H7N9 virus (11).…”

mentioning

confidence: 82%

Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts

Mok

Lee

Lestra

et al. 2014

J Virol

148

126

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A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation. IMPORTANCEA novel avian H7N9 influenza A virus emerged in east China in 2013 to cause zoonotic human disease associated with significant mortality. It is important to understand the viral genetic markers of mammalian adaptation and disease severity in this H7N9 virus. Since many human (but not avian) H7N9 virus isolates have an amino acid substitution at position E627K in the polymerase basic protein 2 (PB2) gene, we investigated the role of this and other functionally related mutations for polymerase activity in vitro, virus replication competence, and pathogenicity in the mouse model. We found that E627K and functionally related mutations are associated with increased polymerase activity, increased viral replication competence, and increased disease severity in mice.

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“…In the first study, 126 healthy healthcare workers and 615 healthy non-healthcare workers were tested for the presence of H7N9 antibodies: one of the serum samples from either group contained a high level of H7-specific antibodies [18]. In another study, 6% (25/396) of poultry workers had elevated titres for antibodies specific for avian-origin H7N9 virus versus none of 1 129 samples tested in the general population [19].…”

Section: Clinical Aspects Spectrum Of Disease and Treatmentmentioning

confidence: 99%

Influenza at the animal–human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)

et al. 2014

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Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.

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Avian-Origin Influenza A(H7N9) Infection in Influenza A(H7N9)–Affected Areas of China: A Serological Study

Cited by 97 publications

References 14 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

Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts

Influenza at the animal–human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)

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