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Emergence of a New Sublineage of Avian Influenza Viruses in Southeast Asia

By Eric Toner, M.D., and Luciana Borio, M.D., November 3, 2006

In an article in the Proceedings of the National Academies of Science published online on October 30, 2006, G. J. D. Smith and colleagues report on the emergence of a new, previously uncharacterized H5N1 influenza virus sublineage in southern China [1]. A virus from this sublineage was first identified in a specimen from a duck in Fujian province, China, in March, 2005, and hence it is called the Fujian-like (FJ-like or FJ-H5N1) sublineage. Since early 2006, it has rapidly become the predominant H5N1 influenza virus sublineage in southern China and has spread to Hong Kong, Laos, Thailand, and Malaysia. Influenza viruses from the new sublineage have also been implicated in 5 human cases of H5N1 infection in different provinces of China.

Ongoing Surveillance Detects Third Wave of H5N1 Panzootic

The authors have previously reported that, since 2003, avian influenza H5N1 viruses of multiple genetically and antigenically distinct sublineages had become established in poultry in different geographical regions of Southeast Asia [2]. Smith’s new report updates the results of ongoing surveillance of poultry from live-poultry markets in 6 provinces of southern China.

From July 2005 to June 2006, 2.4% of poultry in the markets (mostly domestic ducks and geese) were carriers of H5N1. The overall prevalence had significantly increased from 0.9% the previous year. Of poultry that tested positive, the prevalence of the FJ-H5N1 strains increased from 3% of poultry specimens obtained in the summer of 2005 to 95% in the spring of 2006. Thus, FJ-H5N1 sublineage has replaced those previously established multiple sublineages in different regions of southern China.

The authors believe it is likely that the spread of this new sublineage represents a third wave of the H5N1 panzootic. The first wave occurred in early 2004, primarily in Southeast Asia. The second wave started with the outbreak in migratory waterfowls at Qinghai Lake in the spring of 2005 and spread to Europe and Africa. Now this FJ-like sublineage is replacing the previously predominant H5N1 strains throughout much of southern China. 

Reasons for the Emergence and Predominance of the New Strain are Still Unclear

In September 2005, China instituted a compulsory national program to vaccinate all poultry against H5N1 influenza; presumably, all of the poultry tested in this study had been vaccinated. However, a seroprevalence survey of 1,113 chickens from 2 provinces, conducted from November 2005 to April 2006, indicated that only 16% (180) of the birds had detectable HI antibodies (HI titer > 20) against a reference H5N1 virus (Ck/HK/YU22/02). Thus, seroconversion rates are still low.

Of the positive sera, a subset of 76 was randomly selected for a neutralization test. Of those, 55 showed little or no neutralization to the tested FJ-like strain (Dk/FJ/1734/05). The authors state that “chicken in southern China are poorly immunized against FJ-like viruses in comparison with other sublineages,” and speculate that the widespread use of a vaccine that provided immunity to some H5N1 viruses but not FJ-H5N1 created a selective advantage for the FJ- H5N1 sublineage to become predominant. They state that “predominance of FJ-like viruses may be associated with immune escape from the current vaccine strain in poultry.” However, as noted above, only 16% of all the poultry had seroconverted. The paradox of how vaccination could create such selective pressure with such low seroconversion rates is unexplained. 

The New Strain of H5N1 is Expected to be Sensitive to Oseltamivir

Molecular characterization of viruses from the FJ-H5N1 sublineage indicated that they are expected to be sensitive to oseltamivir since they had histidine at position 274 of the neuraminidase protein.  Most, but not all, seemed to be sensitive to amantadine as well. In addition, molecular characterization revealed no mutations associated with increased affinity for human cell surface receptors, meaning that there is no reason the think that this strain is any more likely to cause human infection than other H5N1 strains.

The World Health Organization’s Reaction

The WHO criticized the Chinese government for not sharing viral samples of the new sublineage. In a press report [3], a WHO employee in China stated, “Unless the ministry tell us what's going on and shares viruses on a regular basis, we will be doing diagnostics on strains that are old." Delays in sharing also make it impossible for manufacturers to access the expected efficacy of vaccine candidates under development.

Conclusions

The emergence of a new H5N1 sublineage and the increase in human infections in 2006 suggest that highly-pathogenic avian influenza viruses have not been effectively contained. H5N1 viruses continue to be panzootic. This new report highlights the inherent difficulty in controlling influenza: The virus mutates in a way that allows it to “escape” vaccine, especially when vaccines are poorly immunogenic or not effective against a broad range of strains.

It is not possible to identify sources of human infection if systematic influenza surveillance in poultry is not undertaken. As the authors of this article conclude, control of this outbreak will likely require a much more extensive surveillance network for both humans and animals in which real-time virological and genetic information is integrated with rapid diagnostic testing and vaccine production. 
     

References

  1. Smith GJ, Fan XH, Wang J, et al. Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci 2006. Available at http://www.pnas.org/cgi/content/abstract/0608157103v1 ahead of print. Assessed November 2, 2006.

  2. Smith GJ, Naipospos TS, Nguyen TD, et al. Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam. Virology 2006;350:258-68.

  3. WHO blasts Chinese government for not sharing samples of new bird flu strain. The Associated Press. November 1, 2006.