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LETTER TO THE EDITOR |
Department of Zoology, The University of Hong Kong, China
1 Corresponding author: fcleung{at}hkucc.hku.hk
I write in response to a recent paper entitled "Emergence and predominance of an H5N1 influenza variant in China" published by Smith et al. (2006) in Proceedings of the National Academy of Sciences USA. Webster and Guan, the principal investigators (PI) and correspondence authors, claimed that H5N1 has not been effectively contained and that the virus continued to be panzootic in different types of poultry and emerged to be a previously uncharacterized new predominant Fujian-like lineage. They stated that the low H5N1 seroconversion in live market poultry has facilitated the selection of the Fujian-like strain, and these viruses have already been transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a wave of outbreaks in southeast Asia. They concluded that their findings directly challenge the current disease control measures in that region. I felt that the data reported by Smith et al. (2006) are not convincing and conclusive for them to warrant such conclusions.
First, there were no statistical analyses on any of the data presented. Second, data presentation is inconclusive. Because samples were collected from live-poultry markets from 6 provinces in south China, which is a large area covering a 24-mo period, the authors should have provided details of sources of the positive samples giving the low prevalence rates. Were positive chicken samples all from one market or one province, and were they found along with the positive duck and goose samples? Were the positive duck samples found along with the goose samples, and were they consistently found from the same markets? All these would further provide the understanding of which species may be the H5N1 reservoirs, because there seems to be a lower H5N1 prevalence rate found in chickens than in ducks and geese. Third, not all H5N1-positive samples were sequenced for the phylogenetic analysis, so the calculation of the percentages of virus found from Fujian-like lineage in China may not reflect the real situation. The authors should have explained the rationales for selecting 33 out of 64 (July to September, 2005), 136 out of 412 (October to December, 2005), 113 out of 551 (January to March, 2006), and 108 out of 267 (April to June, 2006) H5N1-positive samples to be sequenced. Again, the most important issue is which market, region, and province were these sequenced samples obtained from? Fourth, the seroconversion data can at best only be viewed as preliminary, because the immunization records of those birds sampled, including which types of vaccine used, were not reported. Fifth, the authors should have presented more H5N1 human-infected data and not only 5 out of 22 human-infected cases in China if they are claiming that those recent human H5N1 isolates from different provinces are all Fujian-like viruses.
The most confusing and astonishing data are the findings that all viruses characterized in this study maintained the motif of the multiple basic amino acids at the hemagglutinin cleavage site characteristic of the highly pathogenic avian influenza and that these viruses also kill embryonated eggs within 24 h of inoculation, which is again a characteristic of the highly pathogenic avian influenza. But these samples were all collected from healthy poultry in live-poultry markets in the 6 provinces. This is not the first time that these authors reported such findings, and possible explanations should be given (Chen et al., 2006). I also noticed that not all the DNA sequences from isolates mentioned in this paper were uploaded onto GenBank. In fact, sequences from isolates mentioned by the same PI in the paper published earlier this year are still missing in the GenBank, given that all PI have signed the agreement to upload their sequences in the open database to share with the wider research community (Chen et al., 2006).
In summary, I would like to acknowledge the hard work of Smith et al. (2006) for collecting and processing 53,220 samples for this study, and I agree with the call for wider surveillance. However, the authors could have put forward a stronger argument to support their claims if they would have presented the whole data set rather than partial disclosures. However, based on the data the authors presented, the emerging of a predominance of a Fujian-like strain of H5N1 claimed is at best preliminary and nonconclusive. Because such reporting would have significant effects toward the government setting and formulating of the influenza control regulation and policy and the poultry industry at large, I would suggest that Smith et al. (2006) be more forthcoming in data disclosure so that the whole scientific community, industry, government, and the general public, can benefit and not have the fear generated by partial disclosures.
It is my opinion that there is an urgency to define and to better characterize the natural reservoir for H5N1 of both high and low pathogenicities, and much more basic research is also needed to study the dynamic of reassortment events among all 8 gene segments of all the avian influenza in the species in which H5N1 resides to gain a better understanding of how H5N1 and other genotypes evolve.
Received for publication November 28, 2006. Accepted for publication November 28, 2006.
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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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