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It is worth noting that this travel log includes H1N1 swine from Asia. The last human was the only reported fatal bird flu case that was not H5N1 (the veterinarian from the 2003 H7N7 outbreak in the Netherlands). The travel log also includes the cases from the 1997 H5N1 outbreak in Hong Kong.
The rapid spread in the human population increases the likelihood of co-infection with H1N1 seasonal flu and the acquisition of key polymorphisms linked to adaptation in human hosts. Two likely acquisitions are NA H274Y and PB2 E627K, which are fixed in human H1N1.
For those who are unaware of what these aquisitions mean, could someone briefly, and simply explain them? I am not good at these explanations.
The acquisition of Lysine at 627 of PB2 allows the virus to replicate more readily at cooler temperatures, meaning upper respiratory system, and therefore could make the virus more transmissable. Sneezes and coughs would spread higher viral loads into the air than is likely going at present with the Swine Flu viruses.
Once the virus spreads more readily throughout a population with no immunity to the virus, then one would expect substantially more hospitalizations and deaths, especially for those with underlying health conditions. So, one (transmission) sort of goes with the other (pathogenicity) to some extent for those at risk.
This movement of swine H1N1 into the human population is cause for concern. The increase over seasonal flu may be driven by the avian PB2 gene in the swine isolate. Position 627 is E, which favors growth at the higher body temperature of birds. Seasonal flu has a K at position 627, which allows for more rapid replication at a lower temperature, which is consistent with the internal temperature of a human nose in the winter.
The presence of avian PB2 may offer a selective advantage over the summer, when seasonal flu falls to barely detectable levels. However, the swine H1N1 that moves south in the upcoming months will be growing under colder conditions, which may favor the acquisition of E627K though reassortment or recombination. This change could create a more virulent H1N1 in the fall in the northern hemisphere.
Thus, the swine H1N1 may be launching a two virus strategy. The H1N1 with avian PB2 will dominate in the northern hemisphere over the summer, while the H1N1 in the southern hemisphere will acquire E627K and establish dominance during the winter months.
Please be aware also that this virus looks in all respects like the variant "iv" types dominated by the New York sequences, however, NA is a mixture that is predominately found in swine viruses. I have not found any human infection isolates with this mix at positions 106 and 247 of NA.
I have located a number of Swine Flu sequences that have the unique combination in NA of V106I and D247N like that of A/Shanghai/71T and the swine isolates. Interestingly, they are are all, without exception, from Japan. We probably should keep a wary eye out for E627K in the Japan PB2 for all future sequences posted.
What would be more favourable for invasion of the lungs? I can see how the avian component would be more beneficial there (presumably the lungs have a higher temperature. But better replication in the upper repiratory tract could also allow for more chances for the virus to invade the middle and lower respiratory tracts.
Wotan (pronounced Voton with the ton rhyming with on) - The German Odin, ruler of the Aesir.
I am not a doctor, virologist, biologist, etc. I am a layman with a background in the physical sciences.
the virus is the Cancun-strain, but it misses 2 of the 11 Cancun markers (C1408T(4),A742G(6)),
the same as Korea/1 and the Japan viruses.
However those have not the other 6 Cancun markers which 71T has.
That could indicate reassortment ?!? 123578 from Cancun,
46 from Japan/Korea
It would also seem that with the development of a more mammalian type of replication gene that higher viral loads could develop quicker in individual patients perhaps leading to some of the faster development of disease we are seeing and be more difficult to fight off. Also the shortened incubation time could increase transmission rates...
Thanks for all the great explanations for lay persons. Also Kent too!
What would be more favourable for invasion of the lungs? I can see how the avian component would be more beneficial there (presumably the lungs have a higher temperature. But better replication in the upper repiratory tract could also allow for more chances for the virus to invade the middle and lower respiratory tracts.
Once the Swine Flu virus has invaded and infected its human host, it seems to have little problem in replicating in both the lungs and the nose where the alpha 2,6 receptors are readily found. And remember, most of the isolates collected from humans are nasal swabs.
However, with the E627K change, the viral loads in the nose will likely be even higher than they are currently. So the virus will still replicate in both the lungs and nose, but with higher viral loads in the nose, the coughs and sneezes will spread more of the pathogen into the air for all of us to breath.
If you think that the current Swine Flu spreads rapidly, hide and watch what happens when E627K becomes predominant. No country has adequate medical facilities to handle the influz of patients that will unsue.
In case any one else out there is asking themselves, "what's Shanghai virus?" as I was, here is an OLD (1990) NY Times article about it. If it is irrelevant, feel free to delete.
I don't understand why, if Shanghai virus was a significant problem in the winter of 1989-1990, it wouldn't ALREADY have acquired the ability to spread easily during cold weather?? But you're saying this is new? And is Shanghai currently widespread? More than other strains of seasonal influenza? I'm confused.
U.S. Health Agency Declares Flu EpidemicBy WILLIAM K. STEVENS Published: Friday, January 26, 1990
Centers for Disease Control declared yesterday [January 25, 1990] that a nationwide influenza epidemic exists and that it is the most widespread outbreak of the disease since 1984-85.
The flu, predominantly a strain called A-Shanghai, has been identified in every part of the country, and major outbreaks have been found in 35 states, epidemiologists at the centers say.
''We're in an epidemic,'' said Dr. Walter Gunn, a specialist in viral diseases at the centers, in Atlanta.
Based on Death Reports
The epidemic was declared on the basis of reports of deaths from 121 cities around the country. The proportion of deaths caused by influenza and pneumonia, a complication of the flu, was higher than expected for the second consecutive week, meeting the center's definition of an epidemic.
Because there is a lag between the onset of the flu and death and because it takes a week or so to report the deaths, the figures actually reflect the incidence of flu in late December and early January, said Dr. Stephen Ostroff, another epidemiologist at the centers in Atlanta.
Ordinarily, he said, the peak of the flu season comes in the middle to the end of February. This year, he said, ''the surge has come earlier, and we don't know whether it's going to subside early.''
Immunization Still Effective
Dr. Gunn urged flu immunization for people older than 65, those of any age who are in ill health ''and anyone who doesn't want to get the flu.''
Symptoms include a sudden onset of fever, chills, sore throat, headache, muscle aches and pains, general malaise and a dry cough. Dr. Gunn said simple gastrointestinal upset, which seems to have afflicted many in the New York region recently, is probably caused by viruses or infections other than the flu unless the stomach distress is accompanied by other flu symptoms.
When the flu kills people, epidemiologists say, it usually does so through pneumonia, which develops as a secondary infection. But it can also cause death through kidney failure and heart attacks, Dr. Gunn said.
Britain Hit by Same Strain
Dr. Gunn said A-Shanghai flu has been associated with more deaths and more instances of severe complications than other strains.
The A-Shanghai virus has also been responsible for Britain's worst flu epidemic in 14 years. Much of Europe, including the Soviet Union, has also been affected. In Britain last month, the epidemic put so many people in the hospital that London hospitals had to cancel thousands of routine operations and accept only emergency admissions.
In an average year in the United State, Dr. Gunn said, the flu plays a role in at least 20,000 deaths. ''This year we think it's going to be worse,'' he added. ''We don't know how much worse.''
In the outbreak in the winter of 1984-85, 57,400 deaths were attributed to the flu or pneumonia.
Linked to 7.6 Percent of Deaths
Last week, 1,132, or 7.6 percent, of the 15,090 deaths reported to the disease control centers from the 121 cities were attributed to flu or pneumonia. The percentage a week earlier was identical. Usually, the figure is between 6 percent and 6.5 percent for those two weeks, Dr. Ostroff said. Not since the 1984-85 season has that usual level been exceeded by as much as it was in the last two weeks.
The centers said that last week 18 states experienced flu outbreaks considered widespread, with outbreaks in counties accounting for more than half the state's population. Seventeen other states experienced regional outbreaks, with outbreaks in counties accounting for less than half the state population.
The epidemic did not begin in any specific part of the country, Dr. Gunn said. Rather, he said, ''it has been all over the place right from the beginning and has kept enlarging.''
The states reporting widespread outbreaks last week were Connecticut, New York, Massachusetts, Michigan, Wisconsin, Minnesota, Missouri, South Dakota, Nebraska, Virginia, North Carolina, Georgia, Mississippi, Oklahoma, Texas, Montana, Idaho and Arizona.
Those states reporting regional outbreaks were New Hampshire, Pennsylvania, Ohio, Iowa, Delaware, West Virginia, Kentucky, Tennessee, Alabama, Arkansas, Louisiana, Wyoming, Utah, Nevada, Alaska, Washington and New Mexico.
Two other varieties of flu, A-Taiwan and Influenza B, have also been detected in limited outbreaks, the first in Alaska, Arizona, Massachusetts and Iowa, and the second in Virginia and Nebraska, Dr. Gunn said. The symptoms are similar to those of A-Shanghai.
Map of the United States showing the influenza outbreaks by state (NYT)
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