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LETTER TO THE EDITOR |
* State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, China; and Virology Division, Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105
1 Corresponding author: yguan{at}hku.hk
F. C. Leung, in a letter to the editor in this volume of Poultry Science, raises a number of questions regarding our recent publication on H5N1 influenza virus in the Proceedings of the National Academy of Sciences USA and concludes that our data were not convincing or conclusive (Smith et al., 2006). Unfortunately, Leung appears to have misunderstood what was actually stated in our paper. At no point did we claim that low H5N1 seroconversion rates had facilitated the selection of the Fujian-like strain. A careful reading of our manuscript shows we state that the mechanism for the emergence and prevalence of a Fujian-like H5N1 variant is still unknown, and at no point do we state that the results of the serology were conclusive. We merely speculate as to a possible mechanism for the emergence of this virus and fully acknowledge in the manuscript that these data were preliminary.
Further criticisms are primarily concerned with a lack of detailed epidemiological analysis of the surveillance data and the fact that not all H5N1-positive samples were sequenced, thereby potentially causing a bias in calculation of the percentage of Fujian-like H5N1 isolates. It is worth emphasizing that we have presented genetic sequence data and analysis of 390 viruses and that there are few other papers reporting such large numbers of new sequences for any other influenza subtypes and none for H5N1. Furthermore, the main thrust of the paper in question was to provide a detailed genetic analysis of the viruses detected in our poultry market surveillance. A detailed epidemiological analysis of this data is now under preparation.
As in our previous publications, we selected representatives of H5N1-positive samples for sequencing based on the date of collection, host, and market. We sampled 20 to 40% of isolates for sequencing from each sampling occasion proportional to the number of H5N1-positive species, except when the number of positive samples was low and it was feasible to sequence a higher percentage (e.g., July to September 2005). Therefore, we believe that the sequences presented would provide a representative picture of the genetic diversity of H5N1 isolated from poultry markets in our surveillance program.
Because the geographical location and host are present in the virus strain name, it is, therefore, possible to infer a preliminary picture of the distribution of H5N1 influenza virus in different hosts and geographical regions from our sequence data. Because almost all of the viruses sequenced are nonidentical, this indicates that the sampling was not biased from multiple positives from a single sampling occasion and also excludes cross-contamination at either market or laboratory levels.
We acknowledge that not all the sequences described in this paper were immediately uploaded to GenBank. This was an oversight on our part, and we acted to rectify this as soon as it became apparent. Submission of the sequences in question was made to GenBank on November 17, 2006, and they were available from December 6, 2006. All other sequence data associated with our previous publications are also publicly available. Furthermore, our laboratory has generated the majority of all available H5N1 influenza virus sequence data, particularly their full genomes. We think, therefore, this criticism is entirely unfounded.
Leung is astonished and confused that highly pathogenic avian influenza (HPAI) viruses can be found in healthy birds in live-poultry markets. This was in fact first demonstrated in Hong Kong in 1997 when over 20% of all poultry markets were found to be affected with H5N1 influenza virus in the absence of massive overt deaths in poultry (Shortridge et al., 1998), and this has been repeatedly shown in our subsequent studies in southern China (Li et al., 2004; Chen et al., 2006). We and others have previously demonstrated that HPAI viruses are maintained and amplified within live-poultry markets. This is because poultry within such markets are continually slaughtered and replenished, and it is therefore likely that little overt mortality will be observed (Kung et al., 2003). In addition, nonsterilizing immunity and partial vaccination coverage may also contribute to the silent prevalence of HPAI in market poultry.
In summary, the data presented fully justify our conclusion that the predominance of the Fujian-like virus over a large geographical region challenges current disease control measures, and we reject the accusation that we were not forthcoming with our data. We were very careful in the interpretation of our data and in the conclusions drawn, and the fact that our results were misinterpreted and misrepresented in the media and other sources does not change this.
Received for publication December 13, 2006. Accepted for publication December 13, 2006.
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REFERENCES |
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Kung, N. Y., Y. Guan, N. R. Perkins, L. Bissett, T. Ellis, L. Sims, R. S. Morris, K. F. Shortridge, and J. S. Peiris. 2003. The impact of a monthly rest day on avian influenza virus isolation rates in retail live poultry markets in Hong Kong. Avian Dis. 47(Suppl. 3):1037–1041.[Web of Science][Medline]
Li, K. S., Y. Guan, J. Wang, G. J. Smith, K. M. Xu, L. Duan, A. P. Rahardjo, P. Puthavathana, C. Buranathai, T. D. Nguyen, A. T. Estoepangestie, A. Chaisingh, P. Auewarakul, H. T. Long, N. T. Hanh, R. J. Webby, L. L. Poon, H. Chen, K. F. Shortridge, K. Y. Yuen, R. G. Webster, and J. S. Peiris. 2004. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430:209–213.[Medline]
Shortridge, K. F., N. N. Zhou, Y. Guan, P. Gao, T. Ito, Y. Kawaoka, S. Kodihalli, S. Krauss, D. Markwell, K. G. Murti, M. Norwood, D. Senne, L. Sims, A. Takada, and R. G. Webster. 1998. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 252:331–342.[Web of Science][Medline]
Smith, G. J., X. H. Fan, J. Wang, K. S. Li, K. Qin, J. X. Zhang, D. Vijaykrishna, C. L. Cheung, K. Huang, J. M. Rayner, J. S. Peiris, H. Chen, R. G. Webster, and Y. Guan. 2006. Emergence and predominance of an H5N1 influenza variant in China. Proc. Natl. Acad. Sci. USA 103:16936–16941.
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