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http://www.influenzareport.com/ir/ai.htm

Infuenza Report

Avian Influenza

(excerpt)

Christian Hoffmann and BSK are editors of HIV Medicine 2005 and SARS 

Reference.

�

Pandemic Risk

Three conditions need to be met for a new pandemic to start:

An influenza virus HA subtype, unseen in the human population for at 

least one generation, emerges (or re-emerges) and

Infects and replicates efficiently in humans and

Spreads easily and sustainably among humans.

              ������

This shows that a threat of a new human influenza pandemic is not 

uniquely linked to the emergence of HPAI H5N1. So far, H5N1 only meets 

two of these conditions: it is, for the vast majority of the human 

population, a new subtype and it has infected and caused severe illness 

and high lethality in more than 140�humans to date. There is no 

immunity against a H5N1-like virus in the vast majority of the human 

population. A new pandemic would be at the brink should the Asian 

lineage H5N1 acquire properties, by stepwise adaptation or by 

reassortment with an already human-adapted virus, for an ef?cient and 

sustained human-to-human transmission (Guan 2004). 

In vitro, it has been shown that two simultaneous amino 

acid exchanges in the receptor binding site of the HA protein of the Asian 

lineage HPAIV H5N1 (Q226L and G228S) optimises binding to human 

receptors of the 2-6 type like that of other human adapted influenza A 

viruses (Harvey 2004). Gambaryan et al. (2006) have already identified 

two human isolates originating from a father and his son infected with 

H5N1 in Hong Kong in 2003, which, in contrast to all other H5N1 isolates 

from humans and birds, showed a higher affinity for 2-6 receptors due to 

a unique S227N mutation at the HA1 receptor binding site.

This instance might be just around the corner or might already have 

occurred while reading this article - no one knows or can foretell. The 

chances for such an event to occur are directly correlated to the amount 

of virus circulating in poultry and, thus, the exposure risks of humans. 

However, it should not be overlooked that while staring at the H5N1 

situation in Asia, other influenza viruses with possibly even greater 

pandemic potential may emerge or may already have emerged in the 

meantime. For example, strains of the H9N2 subtype which was not 

found in Asia prior to the 1980s have not only become widespread in 

Asian poultry populations, but also have crossed efficiently into pig 

populations in South Eastern and Eastern China (Shortridge 1992, Peiris 

2001, Xu 2004). The receptor of these viruses revealed specificities 

similar to human-adapted viruses (Li 2005b, Matrosovich 2001). These 

H9 viruses have a broad host range, are genetically diverse and can 

directly infect man. The H9N2 strain, which was responsible for these 

human infections in Hong Kong, even revealed a genotype akin to that of 

the H5N1 viruses of 1997 (Lin 2000).

Conclusion

The importance of highly pathogenic avian influenza (AI) as a devastating 

disease of poultry has markedly increased during the last decade. The 

introduction of AI viruses of the subtypes H5 and H7 of low pathogenicity 

(LP) from a reservoir in wild water birds has been at the base of this 

process. It remains to be elucidated whether and, if so, why, the 

prevalence of LP H5 and H7 in their reservoirs has also been changing.

Has the Asian lineage HPAIV H5N1 already established endemic status in 

populations of wild and migratory birds?

Can a HPAI virus evolve an attenuated phenotype in wild bird species 

whereby retaining its virulence for poultry?

Is there a role for land-based mammals in the spread of HPAIV?

Is the sequence stretch, encoding the endoproteolytical cleavage site of 

the HA protein, prone to mutations only in the subtypes H5 and H7?

What will be the impact of mass vaccination of poultry against H5N1 in 

Asia - prevention of viral spread or an acceleration of antigenic drift and 

escape

Are shifts in the prevalence of LPAI subtypes H5 and H7 in their natural 

reservoirs potentially affecting also evolutionary stasis?

In particular, the ?rst question is of overwhelming importance - not only 

for the veterinary world. Endemicity of the Asian lineage HPAIV H5N1 in 

migratory birds would pose a constant threat to poultry holdings. This 

would only be met by strict biosecurity measures including a prohibition 

of free-roaming poultry holdings.

As a second line, endemicity in wild birds may also lead to the presence 

of HPAI H5N1 virus in the environment (lakes, sea shores etc.) and might 

pose an additional potential risk of exposure for humans. So far, there 

are no reports of transmission from wild birds or environmental sources 

to humans. All reported human infections, including the most recent ones 

from Turkey, seemed to be acquired following virus amplification in, and 

close contact to, household poultry.

The complexity and the potential impact of the current, zooanthroponotic 

HPAI H5N1 virus semi-pandemic in birds, demands concerted and 

prudent actions from scientists, politicians, and the public.

Influenza Report 2006 is a medical textbook that provides a 

comprehensive overview of epidemic and pandemic influenza. Access to 

the online version is free.

http://www.influenzareport.com/

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Transmission to other Mammals

Avian influenza viruses have been transmitted to different mammal 

species on several occasions. Here, following cycles of replication and 

adaptation, new epidemic lineages can be founded. Pigs, in particular, 

have been frequently involved in such 'interclass transversions'. In 

European pig populations, avian-like H1N1 viruses are highly prevalent 

(Heinen 2002) and an H1N2 virus, a human-avian reassortant virus, ?rst 

isolated in the U.K. in 1992, is constantly gaining ground (Brown 1998). 

In the U.S., a triple reassortant (H3N2) between the classical H1N1, the 

human H3N2 and avian subtypes is circulating (Olsen 2002).

In 2004, 3,000 serum samples obtained from free roaming pigs in 

Vietnam were tested serologically for evidence of exposure to the H5N1 

influenza virus (Choi 2005). Virus neutralisation assay and Western blot 

analysis confirmed that only 0.25�% of the samples were seropositive. In 

experimental infections, it was shown that pigs can be infected with 

H5N1 viruses isolated in Asia in 2004 from human and avian sources.

The highly lethal H5N1 viruses circulating in Asia seem to be capable of 

naturally infecting pigs. However, the incidence of such infections has 

been apparently low. None of the avian and human H5N1 viruses tested 

were readily transmitted between pigs under experimental conditions 

(Choi 2005). Based on these observations, pigs probably do not currently 

play an important role in the epidemiology of the Asian lineage H5N1.

Meanwhile, however, studies in China have revealed the presence of more 

new genotypes of the Asian lineage H5N1 virus in tree sparrows (Kou 

2005). Neither the sparrows from which the viruses were isolated, nor the 

ducks that were experimentally infected with these viruses, showed any 

symptoms. However, upon transmission to chickens, full-blown HPAI was 

provoked. Since different sparrows of the same ?ock carried several 

distinguishable genotypes, which likely arose by reassortment with 

different AI viruses of unknown provenance, it was suspected that H5N1-

like viruses had already been transmitted to these birds some time 

(months?) ago.

Humans

Up until the 30th December 2005, 142 H5N1 cases in humans had been 

reported. The human epidemic is currently limited to Cambodia, 

Indonesia, Thailand, and the epicentre Vietnam (65.5�% of all cases). 72 

(50.7�%) persons have died.

For more detailed information, see the chapter entitled "Epidemiology".

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Edited by Rick