H7N9 Bird flu, Part 1 and tracking

(News & Editorial/ H7N9 Bird flu, Part 1 and tracking)

A.  H7N9 genetic analysis raises concern over pandemic potential
12 Apr 2013, CIDRAP News, by Lisa Schnirring * Staff Writer
Pasted from: http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/apr1213genetic.html

birdflu image

[Photograph above: April 15, 2013 electron microscope image provided by the Centers for Disease Control and Prevention shows the H7N9 virus which can take on a variety of shapes. Almost three weeks after China reported finding a new strain of bird flu in humans, experts are still stumped by how people are becoming infected when many appear to have had no recent contact with live fowl and the virus isn’t supposed to pass from person to person. Understanding how the H7N9 bird flu virus is spreading is a goal of international and Chinese experts assembled by the World Health Organization as they begin a weeklong investigation Friday, April 18, 2013. (AP Photo/CDC, C.S. Goldsmith, T. Rowe) Photo: C.S. Goldsmith, T. Rowe, Associated Press]

A new analysis of H7N9 genetic sequences from the first Chinese patients infected with the virus and from poultry markets found more signals that the virus can attach and replicate efficiently in the airways of humans and other mammals, raising concerns about the virus’s pandemic potential.

The new findings, published late yesterday in Eurosurveillance, are the first detailed comparison of both the human and market sequences. Results are similar to the genetic details of samples from the first three cases reported by Chinese scientists yesterday in the New England Journal of Medicine.

The new results also affirm early observations from some experts that the novel virus has adapted to infect mammals, yielding more information that health officials need to gauge the pandemic threat from the new virus.

The research team from Japan includes Yoshihiro Kawaoka, DVM, PhD, who heads a group at the University of Wisconsin that has done extensive genetic studies on the H5N1 virus, and Masato Tashiro, MD, PhD, director of the World Health Organization Collaborating Center for Reference and Research on Influenza at Japan’s National Institute of Infectious Diseases in Tokyo.

Their look at sequences from influenza databases included human samples from the first two patients from Shanghai, as well as from a woman from Anhui province and a man from Hangzhou province. All of the patients died.

Samples from a market in Shanghai include isolates from a pigeon, a chicken, and an environmental sample.

Phylogenetic analysis of the four human samples suggest they have a common ancestor, with the hemagglutinin (HA) gene part of the Eurasian avian influenza lineage and closely resembling HA genes of low-pathogenic H7N3 viruses detected in 2011 in Zhejiang province, south of Shanghai. The group reported that the neuraminidase (NA) gene closely resembles a low-pathogenic H11N9 virus found in the Czech Republic in 2010.

Internal genes of the H7N9 virus were closely related to H9N2 avian flu viruses that recently circulated in poultry in Shanghai, as well as Zhejiang and Jiangsu provinces, according to the report. Researchers said the findings strongly suggest that the new viruses are reassortants that got their HA and NA genes (the H7 and N9) from avian influenza viruses and the rest of their genes from recent H9N2 poultry viruses.

When they compared the nucleotides from the four human specimens, they found that one of the Shanghai samples and the ones from Anhui and Hangzhou were 99% similar, despite the fact that they came from cities that were several hundred kilometers apart. They found differences between the two Shanghai samples and noted other patterns with the human and market samples that suggest five of the viruses came from a closely related infection source, while one of the Shanghai samples and the one from the pigeon came from different sources.

The Japan group’s findings appear to echo the report from Chinese researchers yesterday that there have been at least two introductions into humans.

The Japanese researchers also detected mutations increase binding to human receptors, a key marker health officials use to gauge the infectivity of new flu viruses. They found that the two Shanghai strains and the Anhui strain had mutations that increase the binding of H5 and N7 viruses to human-type receptors.

One was the Q226L mutation, also flagged by Chinese researchers yesterday. It has been linked to the spread of respiratory droplets in ferrets and was a finding in two controversial studies—one by Kawaoka’s group—in 2012 involving lab-modified H5N1 strains.

“The finding of mammalian-adapting mutations in the RBS [receptor-binding site] of these novel viruses is cause for concern,” the investigators wrote.
The isolate from the Hangzhou patient had a genetic marker (isoleucine at position 226) found in seasonal H3N2 flu viruses.
All seven of the viruses had an HA substitution seen in other recently circulating H7 viruses that has been linked to increased binding to human-type receptors, according to the report.
In the polymerase PB2 protein, they found a marker in the human samples that is essential for efficient replication and has been seen in H5N1 viruses and in an H7N7 sample that was isolated from a fatal case in the Netherlands in 2003.

When they looked for mutations that influence sensitivity to antiviral medications, they projected that all of the human H7N9 samples should be sensitive to neuraminidase inhibitors, except for one of the Shanghai samples. The exception has a R294K mutation in the NA protein that has been linked to resistance in N2 and N9 flu subtypes, which is concerning, the team wrote.

Neuraminidase inhibitors are the most common types of flu antiviral drugs prescribed and include oseltamivir (Tamflu) and zanamivir (Relenza).
Researchers also found some virulence markers, including one at the NA stalk and the other in the PB1-F2 protein; however, they said the human sequences so far lack the N66S mutation that was associated with increased pathogenicity of the 1918 pandemic virus and the H5N1 virus.
The mutation they saw at the NA stalk can occur when the virus adapts to terrestrial birds, which suggests the novel H7N9 virus or their ancestors may have circulated in terrestrial birds before infecting humans. So far, the host of the virus has not been identified, and health officials are considering a range of animals.
The H7N9 virus sequences also showed an NS1 protein sequence pattern that might attenuate the viruses in mammals.

Taken together, the findings present a somewhat clearer picture of the threat the new virus could pose, the group concluded.
“These viruses possess several characteristic features of mammalian influenza viruses, which are likely to contribute to their ability to infect humans and raise concerns regarding their pandemic potential,” they wrote.


B.  H7N9 bird flu strain worries experts
18 April 2013, San Francisco Chronicle, staff writer Erin Allday
Excerpts pasted from: http://www.sfgate.com/health/article/H7N9-bird-flu-strain-worries-experts-4446898.php

birdflu patient

A bird flu that has never before been a problem for humans has infected more than 80 people in China, killing 17 of them, and is raising concerns among infectious disease experts worldwide.

The first human case was identified three weeks ago [end of March], and the rapid compilation of human cases since then has public health officials in China and scientists from around the world scrambling to identify the source of the infection and prevent further spread.
So far, the strain identified as H7N9 does not appear to pass easily between humans. Human-to-human transmission is a critical sign that a virus could reach pandemic levels, such as what occurred with the H1N1 “swine flu” that quickly spread around the world in 2009.
It’s not clear where people have acquired the H7N9 strain. Exposure to infected birds is suspected because the strain is known to circulate among them, but Chinese public health authorities have not been able to identify a specific source. Meanwhile, several cases of possible human-to-human transmission are under investigation, according to the World Health Organization.

“This has very severe potential to be a pandemic in the nature of H1N1, except now we’re talking about a much more virulent virus,” said Dr. Charles Chiu, head of the viral diagnostics laboratory at UCSF. “The one caveat is that we still have not documented human-to-human transmission. While that’s the case, there’s decreased likelihood that it will blow up to a pandemic.”

Pandemic concerns
Public health authorities have worried about the possibility of a deadly pandemic flu for decades, and more urgent alarms were sounded in the late 1990s and again in 2003 when the H5N1 bird flu infected people throughout Asia. That potentially deadly strain of flu so far hasn’t been able to spread easily among people.

In 2009, the so-called swine flu reached pandemic levels, but it proved to be not much more serious than a typical influenza infection in humans. In the past few years, that virus has become a seasonal fixture and preventable by vaccine.

The most recent strain appears to be very aggressive in humans, causing serious illness and death. What’s causing concern among infectious disease experts is that, while it’s unclear that the strain is transmissible between humans, the virus has afflicted far more people in just three weeks than H5N1 ever did in such a short time.

‘Very worrisome’
“Whereas H5N1 is associated with sporadic, rare cases, this one is associated with many more cases in a very short period of time,” Chiu said. “That by itself is very worrisome.”

As of Thursday, 87 cases of H7N9 had been confirmed in China, found in four provinces spread around the country, according to the World Health Organization. The first case was identified March 31, but some of those 87 became sick before then.
The strain causes typical flu symptoms – fever, cough, fatigue and muscle aches – but it progresses to pneumonia in many patients, which is not common in most healthy people who become afflicted with influenza.

Almost all of the cases have been serious and required hospitalization. Infectious disease experts in China have found one case of a boy who was infected with the strain but showed no symptoms, meaning the virus is probably more widespread than the lab-confirmed case counts demonstrate.
One possible bit of good news is that an asymptomatic case may mean the virus isn’t quite as deadly as infectious disease experts feared. Without knowing the total number of people infected in the population at large, it’s impossible for public health authorities to calculate a fatality rate.

“Now that the number of infected people is growing, and the fatality rate is dropping, it’s not looking as severe as it once was,” said Dr. Cornelia Dekker, an infectious disease expert at Stanford and medical director of the Lucile Packard Children’s Hospital Vaccine Program. “That said, we’re still very early into this outbreak, and it remains to be seen what we’re going to learn.”

Aggressive screening
Chinese officials have been aggressively screening people who came into contact with patients who became sick. That screening has identified at least two families with multiple people who were sick, although it’s not clear whether the disease spread from one family member to another or if the people became sick from the same source, such as an infected bird.

So far the virus hasn’t been identified outside of China. U.S. doctors will pay particular attention to patients who come to them with flu symptoms and have recently traveled from China, said Dr. David Lewis, a pediatrician and infectious disease expert at Stanford.
“At this point there’s no need for alarm within the United States,” Lewis said. “Over on our side, we’ll need vigilance for people who develop respiratory symptoms within 10 days of coming back from China. But that’s about all we can do.”

Preparing for a vaccine
The Chinese government has offered samples of the new strain to laboratories around the world, in part to start making preparations for developing a vaccine.

The H7N9 strain is carried in birds but does not typically sicken them. That’s a problem for public health officials who, in cases of other bird flus, will cull flocks that are sick and dying, thus preventing spread to humans. The inability to identify the source of the H7N9 infection creates a greater challenge for officials to stop spread of the disease.

“What they’re hoping to do is put a lid on it by just essentially shutting down the live domestic bird markets. Hopefully that will result in a slowing of spread,” Lewis said. “If (H7N9) is not already in another vector like migratory birds, and if the transmission rate is low – not zero, but low – then that would be reason to be optimistic.”


C.  New strain of bird flu poses pandemic threat
26  April  2013, NewsMedical, Source: The University of Kansas Hospital
Pasted from: http://www.news-medical.net/news/20130426/New-strain-of-bird-flu-poses-pandemic-threat.aspx

The World Health Organization (WHO) is calling the new strain of H7H9 influenza virus “lethal” and The University of Kansas Hospital is preparing now for any potential cases. Although the H7N9 flu strain – or “bird flu” – has not resulted in any confirmed cases in the U.S., authorities want the public to be aware and vigilant about this new strain of flu that is spreading in China and now Taiwan that poses a pandemic threat. Lee Norman , MD, chief medical officer for The University of Kansas Hospital, was briefed on the virus during a recent regional Homeland Security committee meeting.

“This is a brand new strain of flu,” said Dr. Lee Norman . “This is not the H5N1 bird flu that we’ve known about for 15 or 16 years, nor is it associated with the SARS epidemic.  This is brand new, just recently genetically typed out for the first time and there’s a whole lot we don’t know about it.”

Dr. Norman says it is most likely an airborne transmitted disease, but researchers don’t fully yet know how it spreads.  In a video interview, Dr. Norman answers several questions that will help the public understand the virus and be more vigilant, including:

  • Fatality Rates – currently fatality rates are at about 20 percent, which makes this a very dangerous virus
  • Most Impacted – fatalities are following the same general patterns as other flu virus outbreaks, which means that older and younger populations, as well as those with immune issues are more at risk.
  • Vaccines – while there are no vaccines at this time, the CDC is working on investigating this further. Vaccines for other flu strains do not seem to prevent this particular strain.
  • Medical Response – Staff at The University of Kansas Hospital has been briefed on the H7H9 symptoms (which are similar to other flu strains), to be on the lookout for a patient’s previous travel to affected areas, and to follow the CDC guidelines for anti-viral treatment

Dr. Norman advises people traveling to and from China who experience flu-like symptoms should seek immediate healthcare for observation, testing and perhaps isolation.

“We are past the peak seasonal flu and so a person showing symptoms who is associated with travel should drive a higher suspicion,” Dr. Norman said.


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