Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 21, Number 7—July 2015
Letter

Seropositivity for Avian Influenza H6 Virus among Humans, China

Cite This Article

To the Editor: Influenza virus subtype H6 was first isolated from a turkey in 1965 in the United States (1) and was subsequently found in other parts of the world (2). Over the past several decades, the prevalence of H6 virus has dramatically increased in wild and domestic birds (24). In China, highly pathogenic influenza A(H5N1), low pathogenicity influenza (H9N2), and H6 are the most prevalent avian influenza viruses among poultry (5). Although only 1 case of H6 virus infection in a human has been reported worldwide (6), several biological characteristics of H6 viruses indicate that they are highly infectious to mammals. Approximately 34% of H6 viruses circulating in China have enhanced affinity to human-like receptors (ɑ-2,6 NeuAcGal) (2). H6 viruses can also infect mice without prior adaptation (2,7), and some H6 viruses can be transmitted efficiently among guinea pigs (2). To evaluate the potential threat of H6 viruses to human health, we conducted a systematic serologic study in populations occupationally exposed to H6 viruses.

During 2009–2011, a total of 15,689 serum samples were collected from live poultry market workers, backyard poultry farmers, large-scale poultry farmers, poultry-slaughter factory workers, and wild bird habitat workers in 22 provinces in mainland China. A/chicken/Y94/Guangdong/2011 (H6N2), a representative isolate of predominant H6 viruses in mainland China, was used for the serologic testing (Technical Appendix Table 1). Hemagglutination inhibition (HI) assay was performed for all serum samples, and samples with an HI titer ≥20 were verified by a microneutralization (MN) assay, as indicated by World Health Organization guidelines (8). An MN result of ≥20 was considered positive.

The HI result was ≥20 for H6N2 virus in 298 of the 15,689 specimens, and the MN result was positive in 63 of the 298 specimens (overall seropositivity range 20–320, mean 32.7, 0.4%) (Technical Appendix Table 2). The proportion of group members who were seropositive differed significantly according to occupational exposure (p = 0.0125). Seropositivity was highest among workers in live poultry markets, backyard poultry farmers, and workers in wild bird habitats (0.66%, 0.42%, and 0.51%, respectively) (Table). According to χ2 test results, seropositivity among workers in live poultry markets was significantly higher than that among large-scale poultry farmers (p = 0.0015, adjusted ɑ = 0.005. Analysis by unconditional logistic regression model showed that exposure to live poultry markets was a risk factor for human infection with avian influenza H6 virus (odds ratio 2.1, 95% CI 1.27–3.47).

Seropositivity did not differ significantly among male and female persons tested (p = 0.08) (Table). No children were positive for the H6N2 virus. For other age groups, seropositivity ranged from 0.25% to 0.45%, but differences were not significant (p>0.05) (Table).

Of the 22 provinces from which serum specimens were collected, 11 were northern provinces and 11 were southern provinces. Positive specimens were detected in all southern provinces. In northern China, no seropositive results were detected in Henan, Liaoning, or Jilin Provinces. According to χ2 test results, seropositivity in southern China was significantly higher than seropositivity in northern China (p = 0.0375) (Table).

Human infection with influenza H6 virus in mainland China has not been reported, but 63 serum specimens tested in our study were positive for the H6 virus. This level of seropositivity is much higher than that for highly pathogenic avian influenza A(H5N1) virus, for which only 2 of the serum specimens we tested were positive (data not shown), but much lower than the seropositivity level for low pathogenicity avian influenza A(H9N2) virus; 3.4% of the samples tested were positive for A/Chicken/Hong Kong/G9/1997(H9N2)–like virus (data not shown). A previous US study has reported H6N2-positive antibodies in veterinarians (9). Our results and the veterinarian study indicate that the H6N2 virus could infect humans.

In our study, positive samples were detected in 19 of 22 provinces and in all tested worker populations, suggesting that the H6 virus has been broadly circulating in birds in China. Live poultry market exposure is the major risk factor for human infection with avian influenza H6 virus. The limitation of this study is that antigen selection may not accurately detect neutralization antibodies for different subtypes of H6 viruses. Surveillance of the H6 virus in birds and occupationally exposed populations should be strengthened for pandemic preparedness.

Top

Acknowledgments

This study was performed under the serology surveillance system of occupationally exposed populations in China. We are deeply thankful for the contributions of all National Influenza Surveillance Network members, including the China Centers for Disease Control and Prevention in the provinces and in the prefects, all of which collected samples for years. We also thank Ms. Qiao-hong Liao for providing consultation on statistical analysis.

This study was supported in part by the China–United States cooperation project “Developing sustainable influenza surveillance networks and response to avian and pandemic influenza in China” and by the China National Mega-projects for Infectious Diseases (2014ZX10004002).

Top

Li Xin, Tian Bai, Jian Fang Zhou, Yong Kun Chen, Xiao Dan Li, Wen Fei Zhu, Yan Li, Jing Tang, Tao Chen, Kun Qin, Jing Hong Shi, Rong Bao Gao, Da Yan Wang, Ji Ming Chen, and Yue Long Shu

Author affiliations: National Institute for Viral Disease Control and Prevention, Beijing, China (L. Xin, T. Bai, J.F. Zhou, Y.K. Chen, X.D. Li, W.F. Zhu, Y. Li, J. Tang, T. Chen, K. Qin, J.H. Shi, R.B. Gao, D.Y. Wang, Y.L. Shu); China Animal Health and Epidemiology Center, Qingdao, China (J.M. Chen)

Top

References

  1. Downie  JC, Webster  RG, Schild  GC, Dowdle  WR, Laver  WG. Characterization and ecology of a type A influenza virus isolated from a shearwater. Bull World Health Organ. 1973;49:55966.PubMed
  2. Wang  G, Deng  G, Shi  J, Luo  W, Zhang  G, Zhang  Q, H6 influenza viruses pose a potential threat to human health. J Virol. 2014;88:395364. DOIPubMed
  3. Jiao  P, Yuan  R, Wei  L, Jia  B, Cao  L, Song  Y, Complete genomic sequence of a novel natural recombinant H6N2 influenza virus from chickens in Guangdong, Southern China. J Virol. 2012;86:77178. DOIPubMed
  4. Zhao  G, Lu  X, Gu  X, Zhao  K, Song  Q, Pan  J, Molecular evolution of the H6 subtype influenza A viruses from poultry in eastern China from 2002 to 2010. Virol J. 2011;8:470. DOIPubMed
  5. Pepin  KM, Wang  J, Webb  CT, Smith  GJ, Poss  M, Hudson  PJ, Multiannual patterns of influenza A transmission in Chinese live bird market systems. Influenza Other Respir Viruses. 2013;7:97–107.
  6. Yuan  J, Zhang  L, Kan  X, Jiang  L, Yang  J, Guo  Z, Origin and molecular characteristics of a novel 2013 avian influenza A(H6N1) virus causing human infection in Taiwan. Clin Infect Dis. 2013;57:13678. DOIPubMed
  7. Gillim-Ross  L, Santos  C, Chen  Z, Aspelund  A, Yang  CF, Ye  D, Avian influenza H6 viruses productively infect and cause illness in mice and ferrets. J Virol. 2008;82:1085463. DOIPubMed
  8. World Health Organization. Manual for the laboratory diagnosis and virological surveillance of influenza. Geneva. Organization. 2011;•••:6377.
  9. Myers  KP, Setterquist  SF, Capuano  AW, Gray  GC. Infection due to 3 avian influenza subtypes in United States veterinarians. Clin Infect Dis. 2007;45:49. DOIPubMed

Top

Table

Top

Cite This Article

DOI: 10.3201/eid2107.150135

Related Links

Top

Table of Contents – Volume 21, Number 7—July 2015

Page created: June 16, 2015
Page updated: June 16, 2015
Page reviewed: June 16, 2015
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external