Raise Pandemic Concerns in Egypt

Two cases of infection of two brothers in the West, said the four cases were subjected to thorough studies in the central laboratory and the Center for example is 3 and audit by the international reference laboratory of the United Kingdom did not report the results of any mutations in the virus and the infection was caused by infected birds and no cases of infection.

The above translation uses comments from WHO, and sequence data from Mill Hill or Weybridge, to deny human transmission between the toddler cousins (both 2M) in Beheira.  Although no sequences from confirmed 2009 cases in Egypt have been released, the sequence data analysis was likely directed at reassortment, which is a pet pandemic theory of WHO consultants.  They have been trying to identify H5N1 with human flu genes for over a decade, and have no examples.  Although reassortment with human flu genes was involved in the emergence of mild pandemics in 1957 and 1968, the sequences from all eight genes from the 1918 pandemic have no evidence of reassortment.  Moreover, there have been several acknowledged H5N1 clusters involving human to human to human transmission, and these sequences have no human flu genes, which is also true of dozens of shorter clusters which have the diagnostic gap in disease onset dates.

Instead, those sequences support recombination, which involves exchanges of pieces of genes.  Almost all polymorphisms in all eight gene segments from multiple 1918 H1N1 isolates can be found in human H1N1 (A/WSN/33) and swine (A/swine/Iowa/1976/31 or A.swine/Iowa/15/30) H1N1 sequences.  Moreover, attempts to create H5N1 reassortant with human flu genes and enhanced transmission have failed.  Most reassortants don’t grow or fail to grow in mice, in contrast to H5N1 with 8 avian gene segments, which can grow and kill mice.

The ability of H5N1 to grow and kill mammals, including humans, is linked to the polybasic cleavage site, which was not present in prior pandemic sequences.  The components that are lacking are changes in the receptor binding domain which increases transmission efficiency.  Such increases are typically characterized by clusters of cases, such as the recent Beheira cluster, or the Qena cluster in 2007.  Sequences from the siblings in the Qena cluster have been released, and they contain a deletion of position 129, which interacts with the receptor binding domain.  Moreover, analysis of this region matches the profile of H1N1 seasonal flu, which is efficiently transmitted.

Sequences from two of the mild cases in Egypt this season were used in the HA phylogenetic tree in the WHO report on vaccine targets.  The position of the 2009 isolates on the tree suggests these sequences are closely related to the sequences from the Qena cluster, that contain the deletion. This deletion is also acquire via recombination.  The same deletion is in clade 7 sequences from Shanxi and Hunan provinces in China.  Moreover, WHO consultants are largely in denial over recombination.  The deletion in Qena cluster was presented in Toronto at the Options VI conference in 2007, and WHO consultants maintained that the deletion was a “lab error”. However, there are now 13 public sequences from Egypt that have the deletion, and the sequences were generated by multiple independent labs in 2007 and 2008 and involved human and poultry isolates.  These examples are in addition to clade 7 sequences  from China which have the same deletion, supporting recombination.

Moreover, the WHO updates of these clusters have significant omissions.  The disease onset date of the index case in Qena was withheld, and the symptomatic relatives were not mentioned.  Similarly, the Beheira cousins were said to be infected by dead or dying poultry, but no confirmed H5N1 cases have been reported in the area.  Moreover, the fact that the two confirmed toddlers were cousins and next door neighbors were also omitted.  This relationship, and the four day gap in disease onset dates strongly suggests that these cases involved human to human transmission. In addition, WHO has failed to confirm H5N1 in poultry in the area.

However, the relationship between the two H5N1 confirmed toddlers raises enhanced transmission concerns, even if both cousins were independently infected over a four day period.  These concerns of increased transmission efficiencies are increased by the concentration of mild cases in toddlers this year, in contrast to the concentration in children in the spring of 2007.

This change in target population raises concerns that the spread of H5N1 in the human population was much greater than the small number of confirmed cases.  Less than 1% of hospitalized suspect cases are PCR confirmed and the cases in the Spring of 2007 and 2009 were mild and could reflect a large population that either tests negative or is not tested at all because of resolution without treatment, or treatment as seasonal flu.

The above data raises concerns over reliance of lack of human flu genes as evidence for a lack of human transmission, and the failure to understand how influenza evolves and expands its host range.