AVPA/Conferences/February 2007/The case against H5N1 human pandemic
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The case against H5N1 human pandemic – A chook vet perspective
By George Arzey
The mechanisms proposed for human pandemics are reassortment and mutation. The three requirements for emergence of a human pandemic are regarded to be a new virus emerging through a reassortment or by gradual mutation for which the human population has little or no immunity, ability to replicate in humans & cause disease; and the virus needs to be highly contagious between humans.
An additional supporting argument for the apocalyptic nature of H5N1 are that most pandemics originated in China –the epicentre (H5N1), human pandemic is overdue, the H5N1 viral load is unprecedented in poultry & wild birds in some areas, “once the virus gets into the AIDS Continent…” and the broadening the number of species affected with AIV (NEJM, Nov 2005) (cats, dogs, pigs, leopards etc.)
The paper discusses these arguments, with emphasis on the following aspects:
The role of China as the epicentre of human pandemics could be challenged when historical data is analysed – Only 23% of the known human pandemics in the last 500 years have definitely originated in China.
Is the pandemic really overdue?
Consideration of the standard deviation from the mean periods between pandemics could reveal that the next pandemic is not due until 2032.
Generally, there are quite a few renowned scientists that believe that no predictable pattern of pandemic periodicity exists” Dowdle R (Emerging Inf. Diseases Vol 12 Jan 2006) and speculations as to the timing of the next pandemic are unrewarding (Potter in Chronicles of Influenza pandemics 1998). Despite explosion of data on the 1918 pandemic we are not much closer to understanding pandemic emergence in 2006… (Taubenberger et al Emerging Infectious Dis Vol12 Jan 2006.
The reassortment potential
Human infection (virological surveillance demonstrated co-circulation of H5 and human AIV (WHO Jan 2005) and it appears that in the past 10 years this virus seems to have had every chance to reassort and acquire human transmissibility and the fact that it has not, may mean it will be unlikely to do so in the future” (G Laver).
H5N1 infection was reported in a variety of mammals in SE Asia and Europe but not one reassortment with mammalian AIV viruses has been found. Also H9N2 of similar gene composition, despite wide circulation, has not acquired genes from non avian source.
In Turkey in January 2006 a human patient with a mixed population of H5N1 demonstrated that H5N1 has already crossed the so called species barrier. Some of the mixed H5N1 population have been associated with sequence associated with increased affinity with Sal 2;6 Gal-the human receptor, yet a pandemic has not emerged.
PNAS (August 2006 vol. 103 | no. 32 | 12121-12126) reported that H5N1 mixed with 4 or 6 human virus internal protein genes - reduced replication and no transmission. Thus the acquisition of human virus genes was insufficient for H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host.
Credible arguments could be mounted to show that between 1889 – 1977 human pandemics and epidemics demonstrate a cyclical pattern that support the proposition that only certain HA subtypes are capable of a human pandemic.
A similar cyclical pattern is evident in pigs. The 2 HA subtypes involved in all major epidemics in pigs are the H1 and H3. Despite exposure to some of the most common other HA subtypes like H9 or H4, reassortments with other than H1, and H3 subtypes have not been reported in pigs despite co-circulation and despite the fact that the pig is believed to be the ultimate mixing vessel.
Surveys in the bird markets in China demonstrated that the viral load of H3, H6, H9 and H11 far exceeds the H5N1 viral load (6.0% vs. 1%) (Chen et al PNAS Feb 2006)
Historically it can be demonstrated that enormous viral loads of H5 and H7 in poultry did not result in the emergence of a human pandemic or epidemic.
Although there are perceptions of a widespread presence of H5N1 in wild birds, surveys in the EU and SE Asia can’t support this proposition.
Mutation
The acquisition of the entire AI viral genome from birds or other mammals – adaptive mutation (the 1918 pandemic) is another mechanism regarded by many to enable a human H5N1pandemic This is not regarded as the main mechanism (Alexander, Capua & Brown, (library.wur.nl/frontis/avian_influenza/01_alexander.pdf , Webster RG, (J Infect Dis. 1997 Aug;176 Suppl 1)
No known mutation correlated with high pathogenicity in animal AIV has been found in the 1918 virus. None of the known human epidemics / pandemics was a result of highly pathogenic virus. There was no association with poultry AIV in last century pandemics or epidemics. The majority of H5N1 AA (and H9N2) does not corresponds to “human like” residues and none of the AA of the PB1 of the H5N1 were typical of any of the human H1, H2 or H3 subtypes.
The 1918 pandemic could be regarded as a unique event. It is being suggested that it started in the winter of 1916 in a British camp in N. France (Vaccine Vol 23, 2005) and coincided with the explosive usage of gases, among them mutagenic gases like mustard gas in the winter of 1916. The unprecedented accelerated rate of nucleotide and amino acids changes (50 x the expected normal rate) in the 1918 flu virus could perhaps be explained by the unprecedented usage of mutagenic gases on the Western Front between 1916 and 1918.
In conclusion while many events are possible it is important to understand the differences between probable and possible.
