Category: swine flu

Nov 25 2009

H1N1 With Hemorrhagic Pneumonia May Be Increasing In US

It was recently reported in Iowa that deaths from H1N1 may be under-reported. Although the official death toll for the state is 21, the Polk County medical examiner

said he has performed autopsies on some residents who were never diagnosed with H1N1, but actually had it.”In the autopsy, what we’re seeing is very heavy, wet hemorrhagic lungs, lungs with a lot of blood in them,” said Dr. Gregory Schmunk.He said the official count of seven H1N1 deaths is inaccurate, but patient rights laws prohibit him from giving specific numbers.He said there are two reasons for the discrepancy. First, not all sick patients get tests and second, the virus is difficult to detect. Some patients may be too sick to receive the most accurate H1N1 test.

He also pointed out that it is vital for people to get the flu shot when it is available, and for people who are sick to stay home, since one sick person at work can infect 10 others.

This may be the H1N1 variant that has been ravaging people in Ukraine, Norway, and now starting in China. Well over 1.6 million people have been infected in Ukraine alone in the last few weeks, and many are dying of hemorrhagic pneumonia. It has been reported that many of the dead victims had black lungs that had been totally destroyed in a matter of a couple of days. This is believed by some researchers to be caused by the receptor binding domain change, D225G, which was also identified in the 1918 and 1919 Spanish flu pandemic that killed many millions of people, as reported in a recent posting at recombinomics.

Betsy McKay: I just wanted to follow-up on the question about the mutation in norway.  I wondered if you could talk a little bit more about is it possible that this mutation has produced a more virulent form and what has CDC uncovered through its own work?

Anne Schuchat: this mutation has been seen sporadically here and there around the world.  Sometimes it’s been seen in patients who had very mild disease and sometimes it’s been seen in people who had more severe or fatal disease.  And, of course, lots of virus without this mutation has been seen in the fatal as well as the milder forms of H1N1 influenza.  There’s some theoretical reasons why this particular mutation might lead an influenza virus to live easier in the deep part of the lungs and cause lower respiratory infections, but we’ve actually seen lower respiratory infections in a severe viral pneumonia without this mutation.  So I think it’s too soon to say what this will mean long term.  It’s an important finding and they’re looking into it, but I don’t think it has the public health implications that we would wonder about.  Did you have a second question?  Oh, what have we seen so far?  I believe it’s been seen in the U.S. But associated with mild disease.  I believe.  I might need to verify that.  Do we have another from the room?  Okay.  We’ll go back to the phone.

The above comments are from the latest CDC update and regard the receptor binding domain change, D225G, which has recently been reported in Ukraine and Norway.  This change was also identified in 1918 and 1919 fatal lung cases and the change has been targeted in receptor binding domain studies.  These studies showed that the 1918 H1N1 with D225G was able to bind to gal alpha 2,3 and gal alpha 2,6, in contrast to the 1918 sequences with wild type D225, which targeted alpha 2,6.

Recent studies have also demonstrated that alpha 2,3 receptors are on alveolar epithelial type II cells, which regulate lung surface tension as well as immunological defenses which include the release of cytokines.  Binding of H1N1 to these cells could have significant clinical implications, which is supported by the recently published sequences which identifies D225G in lung and trachea samples form fatally infected patients.  The cases in Ukraine were also linked to hemorrhagic disease and the CDC sent out a warning on such cases due to sporadic reports in the United States.

In another article on the recombinomics web site, yesterday, that the situation in Ukraine is critical:

Ukraine Dead Approach 400 – D225G Spreads
Recombinomics Commentary 23:30
November 24, 2009

1,679,237 Influenza/ARI

99,661 Hospitalized

397 Dead

The above figures from the latest daily update from the Ukraine Ministry of Health support a decline in the rate of increases of cases and deaths, but the total is now almost 400 fatalities (see map).  The spread was likely slowed by the country-wide closing of schools along with warmer weather.  However, it is likely that the virus will return as temperatures drop and the traditional flu season begins, although it is unclear if seasonal flu will be in circulation in 2010.

The receptor binding domain change, D225G, was in four of four sequence from fatal cases, raising concerns that the 2,3 alpha specificity of D225G drove the H1N1 to the lungs and the total destruction.  Three patients in Norway were said to also have D225G, and two of the three died while the third had been in serious condition.  25 HA sequences from Norway were deposited at Genbank, but only one had D225G, and it was a mixture.  In Brazil both patients with D225G in lung samples had died, and the case in China had been in serious condition.

This is a critical situation that must be closely monitored. Up until now, H1N1 has been pretty mild, but it does seem to be mutating to a much more virulent variety. Also, there has been a lot of evidence of people who had previously had H1N1, earlier in the year, being re-infected. This is further evidence of mutations of the virus.

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