Rhiza Labs FluTracker Forum

The latest comments from the CDC on the paper from Norway detailing the linkage of D225G and D225N to severe and fatal cases are part of a shell game with mild cases from April. These cases only have D225G in isolates grown in eggs indicating that either the D225G is a lab artifact in these cases or D225G is at low levels in the original samples. Either explanation would explain why the cases were mild.

However, in the WHO preliminary D225G analysis where half of samples with D225G were from fatal cases, the mild cases were included to lower the frequency, and when D225G frequencies in the US were cited, these cases were excluded.

Thus, these cases really amount to a shell game, where mild cases are included to lower the CFR, and excluded to claim that D225G is rare in the US.

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From WHO report:

Surveillance and laboratory analysis efforts to study this substitution have given priority
to specimens from hospitalized and severely ill patients, leading to potential biases in
the data. Additionally, a study done by the WHO Collaborating Centres for Reference
and Research on Influenza (WHOCC) in Atlanta located in the Centers for Disease
Control and Prevention (CDC) found the D222G substitution in 14 virus isolates but not
in viruses in the original clinical specimens indicating the D222G substitution in these 14
virus isolates occurred after growth in the laboratory. These observations have made
determining the clinical relevance of this substitution difficult.

http://www.who.int/csr/resources/public ... iruses.pdf

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Some countries have reported the D222G mutation only in mild cases, while others have seen it as statistically linked with severe illness, but the latter didn't rule out possible confounders, Cox said. She reported that the CDC has found the mutation in a total of eight cases, of which five were nonfatal. Some of the nonfatal cases were mild.

http://www.cidrap.umn.edu/cidrap/conten ... ation.html

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D225G (CDC)
name age/gender date
A/Texas/05/2009 16M 4/15/2009
A/Texas/11/2009 9M 4/23/2009
A/Georgia/01/2009 12F 4/27/2009
A/New York/04/2009 17F 4/2009
A/Illinois/10/2009 55M# 7/31/2009
A/North Carolina/53/2009 53M 10/18/2009

mixture with wild type
A/New York/31/2009 14F 4/24/2009
A/New York/11/2009 16F 4/25/2009
A/California/13/2009 4/21/2009
A/Texas/10/2009 6F 4/23/2009
A/California/07/2009 54M 4/9/2009
A/Nebraska/02/2009 48M 4/2009
A/Texas/04/2009 16M 4/14/2009
A/Utah/42/2009 28F$* 7/24/2009
A/North Carolina/39/2009#* 43F 10/15/2009

# = H274Y
* = known or likely fatal
$ = D225N mixture

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Claiming 8 cases positive for D225G when the CDC has already published D225G postive sequences from 15 cases means that not only is the CDC relying heavily on negative data, but is declaring false the positive data that says the negatives are false.

Declaring positive data false is very dangerous, espcially when the positive data is generated by growing the virus in eggs, which have the same gal 2,3 receptors as found in human lungs, where D225G does its damage.

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Here is a quick review on early D225G detection and implications. In the initial sequences, including California/7, D225G could be found in virus grown in eggs, but not in direct sequencing or in virus grown in mammalian cells. This data could be interpreted in two ways. One is the D225G was an artifact and was not present in the original sample. The other was that it was at low levels in the original sample, and was only detected in eggs because D225G has an added specificity of gal 2,3 which is the receptor in the eggs, so D225G is selected (in mammalian cells, the D225 out competes the D225G because of strong gal 2,6 preference by D225). This alternate view holds that eggs are just a more sensitive assay for detecting low levels of D225G, and knowledge of the frequency of low levels of D225G would be important.

The CDC clearly took the eggs as artifact interpretation and they no long test (or at least no long disclose) in eggs, so only samples with high levels of D225G are identified (through direct sequencing or growth in mamamlian cells).

Moreover, the vaccine target selected for the shot does not have D225G. As a result the virus target without D225G grows more slowly in eggs, which led to to lower yeilds and a delay in vaccine shipment, resulting in vaccinations AFTER the peak of the fall wave. In contrast, the live vaccine (made by Medimmune) that has D225G grew well in eggs and shipped weeks ahead of the shot.

Consequently, the more important D225G is, the dumber the decision to exclude it from the vaccine traget becomes (and this exclusion was not only last spring, but also in the most recent recommendation, which says that vaccines stocks lacking D225G are fine because they meet the definition of California/7-like.

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I had been thinking it was the opposite case, that D225G had difficulty replicating in eggs and that it was both a time and money consideration that had contributed to leaving it out of the vaccine equation. Yes that is DUMBER.

These impromptu lessons are highly appreciated, thanks.

So there could be a lot of D225G out there, albeit at low levels, that isn't being picked up because insensitive testing is being used?

I just don't get why the WHO and CDC are either ignoring or covering up the D225G issue.

D225G is a double whammy for CDC and WHO. First, it makes the decision to exclude it from the killed vaccine look VERY bad, and second it destroys their "random muation" paradigm (and supports recombination).

Thus, an important D225G is the CDC's and WHO's worst nightmare, for all the WRONG reasons.

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Actually, D225G is more than a double whammy, because it also was PREDICTED for Ukraine,

http://www.recombinomics.com/News/11090 ... _1918.html
http://www.recombinomics.com/News/11180 ... D225G.html

and WHO/CDC say influenza is not predictable, especially single nucleotide changes, which are said to be caused by copy ERRORS.

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