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H5N1 2005 Pandemic at Phase 5 or 6?
Recombinomics Commentary
May 22, 2005
>> The risk of a major pandemic of influenza remains unquantifiable. There have been more apparent clusters of human avian influenza virus infection in the north of Viet Nam than in the south of Vet Nam or elsewhere, but in virtually all situations, there has been exposure to or consumption of diseased chickens. There is still no firm evidence that the H5N1 virus transmits directly from human-to-human, although this
possibility cannot be excluded. Although the avian influenza viruses isolated from humans appear to be more heterogenous in terms of the nucleotide sequence of the hemagglutinin gene (which encodes the virus
protein that binds to the virus receptor on the surface of host cells), it should not be concluded that the virus may be changing to a form capable of human-to-human transmission. There is no directionality in virus variation unless there is an external selective force favoring a particular change. It is possible that a virus capable of transmission between humans may evolve by chance, but there is no reason to suppose that such a virus evolving by mutation alone would be exceptionally virulent, rather the reverse. In the H7N7 avian influenza outbreak in the Netherlands in 2003, many poultry workers developed mild infections (conjunctivitis) with very limited spread to household contacts, but no pandemic ensued. The greatest risk remains the generation of a novel human pathogen by reassortment of genes between the H5N1 avian virus and human influenza viruses. - Mod.CP] <<
The above commentary on lack of human-to-human transmission simply misrepresents the available data. The association with poultry, especially in 2005, is similar to observations that virtually all index cases in clusters woke up on a Tuesday and developed bird flu symptoms within 7 days.
Most of the associations between index cases of clusters with poultry have been extremely weak. Blood pudding meals, meals at neighbors, proximity to slaughter houses etc, provide little evidence for a causal relationship. Others who ate the same meal had no symptoms or evidence of exposure, and the index cases generally developed symptoms too soon or too late after the suspect meal.
The evidence for human-to-human transmission was overwhelming in 2004. Common exposures generally produce symptoms at the same time, while human-to-human transmission produce a bimodal distribution of disease onset dates. The familial clusters at the beginning of 2004 were bimodal, strongly suggesting human-to-human transmission in all or most clusters. Last summer larger clusters in Vietnam and Thailand left little doubt that the familial clusters were generated by localized human to human transmission, which placed the pandemic at phase 4.
In 2005 the size of the bird flu clusters grew larger and the clusters began to cluster, moving the 2005 pandemic to phase 5, which is define by larger localized clusters. The real question at this time is whether level has moved to 6, due to widespread community transmission that is not recognized by because of lack of testing or reporting.
The genetic changes currently being reported in northern Vietnam are due to additional recombination. These changes are far from random and accumulate in the population due to selection advantages.
H5N1 has been evolving via changes in genes due to recombination. There has been no reassortment with human genes and little reason to expect such recombination. Human pandemics last century were driven by a change in the hemagglutinin gene. 1918 was caused by H1. 1957 was caused by H2. 1968 was caused by H3. There is no reason to expect the pandemic of 2005 to be caused by a reassorted H1 or H3. H5 is being modified to cause the 2005 pandemic. No reassortment required.
WHO has stopped proclaiming the absence of human genes in H5N1 isolates. The "novel human pathogen" is H5, with an expanded host range, not H5 swapped back to H1 or H3. Such a mechanism has never made any sense, and it is unfortunate that the editor of a widely read newsletter like ProMed would continue to post such comments at this stage of H5N1 evolution.
Human-to-human transmission of H5N1 is well established. The only real question is whether the current pandemic is at phase 5 or the final phase 6.
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