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Genetic Changes in Pandemic H1N1 in Brazil Raise Concerns Recombinomics Commentary 19:40
July 29, 2009
"The family Laguna had eight other cases of swine flu confirmed: mother, father, younger brother, three cousins, grandmother and an aunt of the girl. .
The above translation describes pandemic H1N1 infections in family members of the first confirmed H1N1 fatality in the Sao Paulo metropolitan region. The 11 year old girl, from Osasco (see map) died on June 30 and H1N1 was isolated from her blood on July 3. The HA sequence of the isolate, A/Sao Paulo/43812/2009, was released at Genbank and has three newly acquired polymorphisms. One polymorphism encodes for V252M (H3 numbering) and the nucleotide change is found in a limited number of sequences, including those from the 1918 pandemic. Other human H1N1 sequences include 2006 isolates from Peru and H1N1 isolates in circulation prior to the 1957 H2N2 pandemic. These human isolates have V252I. However, V252M is found in the 2001 swine isolate from Hong Kong, A/swine/Hong Kong/NS1659/2001 (see list here).
The second change also is non-synonymous (Q296H), and is found in multiple 2009 pandemic sequences identified worldwide (see list here), including an earlier isolate from Sao Paulo, A/Sao Paulo/2233/2009.
The third change is synonymous and also found in 2009 pandemic sequences (see list here), which are distinct from the isolates sharing the second polymorphisms. However, the synonymous polymorphism is also in the Hong Kong swine isolate providing additional evidence for acquisition via recombination.
This Sao Paulo isolate is the most recent isolate from Brazil, and may represent a change associated with the dramatic rise in fatalities in the region. Almost all of the fatalities in Brazil are in the southern region, and a high rate of fatalities has also been reported for adjacent locations in Argentina (see map). This concentration of fatal cases in southern Brazil and the Buenos Aires / Santa Fe region in Argentina and locations to the north, raise concerns that the fatalities may be linked to genetic changes in the pandemic virus circulating in the area. The present of the novel polymorphism, V252M, increases those concerns.
Recent reports from Argentina indicated there were 8 amino acid changes in recent isolates, presumably spread across all eight gene segments. The relationship of these changes to the newly acquired polymorphism in the Sao Paulo isolate would be of interest.
Release of recent sequences from isolates in Brazil, Argentina, Uraguay, and Paraguay would be useful.
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
Does this occur with seasonal flu? If not, is this something to be concerned about?
The fatal cases have their organs turned into mush by a cytokine storm. This is tissue destruction on a massive scale and the dying patient becomes viremic.
The fatal cases have their organs turned into mush by a cytokine storm. This is tissue destructi on on a massive scale and the dying patient becomes viremic.
We know from post mortems that that was true in 1918, and we know that has been true in some cases where H5N1 is the pathogen. Do we have post mortem evidence that that is occuring in H1N1 cases? Or, is it just ARDS (cause enough)?
We know from post mortems that that was true in 1918, and we know that has been true in some cases where H5N1 is the pathogen. Do we have post mortem evidence that that is occuring in H1N1 cases? Or, is it just ARDS (cause enough)?
Cases have been described as having organ failure and kidney failure. Kidneys fail because they can't clear the garbage created by massive cell destruction.
This is a 1918 re-run. Its just a matter of scale.
That is the strongest statement I have read yet. Can you give a little more detail on the scale of the rerun. Would you say that today we are at a one or two on a scale of ten?
That is the strongest statement I have read yet. Can you give a little more detail on the scale of the rerun. Would you say that today we are at a one or two on a scale of ten?
All developments to date are on a 1918 track.
Its the real deal, but still a bit early to call the scale.
Cases have been described as having organ failure and kidney failure. Kidneys fail because they can't clear the garbage created by massive cell destruction.
This is a 1918 re-run. Its just a matter of scale.
Cases have been described as having organ failure and kidney failure. Kidneys fail because they can't clear the garbage created by massive cell destruction.
This is a 1918 re-run. Its just a matter of scale.
I'm not a physician, and, if you are, I am not aware of it. But, it seems to me that kidneys can fail for other reasons than they '..can't clear the garbage...'
I seem to recall that with H5N1, they actually found the virus replicating in organs other than the lungs. Is there evidence of the same with swine H1N1.
I don't mean to diminish the threat, or your 1918 parallels (because I find it compelling), but '...fatal cases have their organs turned into mush by a cytokine storm... seems a bit strong for a scientist of your stature.
Have we actually found evidence of viral replication in organs other than the respiratory tract, wether they turn these organs to mush, or not?
I don't mean to diminish the threat, or your 1918 parallels (because I find it compelling), but '...fatal cases have their organs turned into mush by a cytokine storm... seems a bit strong for a scientist of your stature.
Have we actually found evidence of viral replication in organs other than the respiratory tract, wether they turn these organs to mush, or not?
I don't think Dr. Niman is being strong in his statement:
Page 220-221:
"....why should the sickness affect so many organs of the body normally untouched?...most often the disease resembled encephalitis, with the patient lapsing into a coma...a dilation of the heart but even of fatty degeneration...a cough so intense that it ruptured the muscles of a soldier's rectum...retention of urine...puffy faces and swollen ankles of acute nephritis...the lungs were the organs most vitally affected...a patient's face so contorted in death that even close friends couldn't recognize him...and autopsy surgeons were encountering what one doctor termed 'a pathological nightmare'; lungs up to six times their normal weight, looking 'like melted red currant jelly.'"
Page 7:
"In the open chest of a cadaver Welch saw the blue, swollen lungs of a Spanish Influenza...Cause of death? That at least was clear: what in a healthy man are the lightest parts of his body, the lungs, were in this cadaver two sacks filled with a thin, bloody, frothy fluid.....The lungs of those who died quickly, sometimes only 48 hours after the first ache and cough, were such as he had never seen before...Their most conspicuous feature was the enormous quantity of thin, bloody fluid. It oozed out of their lungs sectioned for examination, and in the large air passages leading to the throat it mixed with air in a bloody froth. As rigor mortis set in, the fluid often poured from the nose and stained the body wrappings."
I'd like to add that we often ask Dr. Niman to explain scientific findings in layman terms...I think his statement explains it clearly enough that we all get the point.
.........Have we actually found evidence of viral replication in organs other than the respiratory tract, wether they turn these organs to mush, or not?
They described the cases of 10 patients at a Michigan hospital .....
MULTIPLE ORGAN FAILURE
Nine had multiple organ failure, which can be seen in influenza, but five had blood clots in the lungs, and six had kidney failure
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
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