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A few years ago, back in January 2009 (and six months before the swine flu pandemic),  I wrote a blog regarding H5N1 and the potential for chickens to be asymptomatic carriers of a pandemic candidate virus. 

If you performed a Find and Replace using "H7N9" for "H5N1" in that blog post, you would instantly have a very topical blog.  So please read that blog from four years ago, and change the virus subtype in your head as you go along.

Now, I vector you to today's disclosure that 64 human H7N9 cases exist in six different provinces, including two fabled cases in the city of Beijing.  There are 14 deaths.  As I mentioned in one of my earliest blogs on the subject of human H7N9, barely a week ago:

Dr. Yin of the Bill and Melinda Gates Foundation.  Apparently Dr. Yin is the Foundation's leader in China.  And it was quite satisfying, knowing Bill and Melinda are spending funds in  China, including, but not limited to, surveillance.  Dr. Yin's statement is worth paraphrasing.  He said, basically, if you don't test for H7N9, you won't find it.  But if you do test for it, you'll find it.  The inference is that there have been numerous unexplained and undiagnosed severe respiratory ailments there this season.  Retroactive testing of samples, based on Dr. Yin's inference, will yield a significant increase in the number of H7N9 human cases. 

Indeed, with more than 400 labs across China testing away, they are finding more cases in more geographic locations.  Simultaneously, more deaths are being reported.  Fortunately, the deaths are not increasing in proportion to the number of confirmed cases.  We all believed that the case fatality rate would not be as high as the initial reports would have indicated; the sample was too low and the data, therefore, did not support (yet) a high CFR.

But I found it interesting that as of this morning, the WHO has not yet established a pandemic alert system for H7N9. Dedicated Web page, yes.  But the WHO has not started an alert system. 

WHO has an alert system in place for H5N1, and had one for pH1N1, a.k.a. The Virus Formerly Known As Swine Flu.  Perhaps it is too early for such an alert system.  After all, the virus is only in one region of one nation (albeit a region that is host to more than 300,000,000 Chinese).  I also understand the reluctance the WHO must feel regarding this disease.  The WHO took significant credibility hits after swine flu, some referring to the WHO as "chicken little."  These criticisms are unfair and undeserved.  No one had any idea that pH1N1 would have been as mild as it was.

And "mild" is a misnomer.  The words "mild virus" are of great consolation to virus experts, public policymakers and public health professionals who look at The Big Picture; but those words are of little consolation to the parents of children who died during the pandemic. 

A Reuters story from June of last year paints that smaller picture.

(Reuters) - The swine flu pandemic of 2009 killed an estimated 284,500 people, some 15 times the number confirmed by laboratory tests at the time, according to a new study by an international group of scientists.

The study, published on Tuesday in the London-based journal Lancet Infectious Diseases, said the toll might have been even higher - as many as 579,000 people.

The original count, compiled by the World Health Organization, put the number at 18,500....

The results paint a picture of a flu virus that did not treat all victims equally.

It killed two to three times as many of its victims in Africa as elsewhere. Overall, the virus infected children most (4 percent to 33 percent), adults moderately (0 to 22 percent of those 18 to 64) and the elderly hardly at all (0 to 4 percent).

Even though the elderly were more likely to die once infected, so few caught the virus that 80 percent of swine flu deaths were of people younger than 65.

In contrast, the elderly account for roughly 80 percent to 90 percent of deaths from seasonal influenza outbreaks. They were probably spared the worst of 2009 H1N1 because the virus resembled one that had circulated before 1957, meaning people alive then had developed some antibodies to it.

The relative youth of the victims meant that H1N1 stole more than three times as many years of life than typical seasonal flu: 9.7 million years of life lost compared to 2.8 million if it had targeted the elderly as seasonal flu does."

So swine flu was much more of a force than anyone (especially the critics) thought it was.

Here in April of 2013, we have a big problem.  No one knows how long this new H7N9 virus was circulating among wild birds, poultry and (especially) people in China.  In fact, we didn't know Diddley until March 31st, when the Chinese sprung the news upon the world.  Exactly when the Chinese knew it had H7N9 in people is cause for speculation, but I think we can excuse the Chinese for demanding confirmation before telling the whole world (to their credit) that a new pandemic candidate was emerging within their borders.

In fact, nothing may have ever been known, had the cases involving the three male family members not caused some doctor or technician to begin testing for something.  My guess is they speculated it was  seasonal influenza or H5N1 bird flu, then moved to SARS, then moved to the new novel coronavirus NCoV, and then reverse PCR testing revealed the presence of H7N9. 

Thank the Maker that someone had the curiosity and the desire to test in a wider spectrum!

Adding to the drama is the report from Beijing last week that a 4-year-old boy tested positive for H7N9.  He is not sick and displays no symptoms, yet he is an asymptomatic carrier of bird flu. This means wider testing is essential -- of humans, pigs and birds.  The testing net needs to be cast very widely in order for everyone to get their arms around the problem. 

And that, folks, is why I believe the USA's CDC opened its Emergency Operations Center at Level 2.  Since the CDC EOC alert levels only go from 3 to 1, the opening at Level 2 was considered by some to be controversial.

Knowing now what we do, and analyzing their decision in the current light, we should say this was an important and prudent decision.  Because, folks, we don't really know if this virus has come to America or not. And the only way we are going to know anytime soon is through weekly surveillance of mortality and morbidity.

From Wikipedia:

 United States

On April 9th, 2013 the Centers for Disease Control and Prevention (CDC) activated its Emergency Operations Center (EOC) in Atlanta at Level II, the second-highest level of alert.^[30] Activation was prompted because the novel H7N9 avian influenza virus has never been seen before in animals or humans and because reports from China have linked it to severe human disease. EOC activation will "ensure that internal connections are developed and maintained and that CDC staff are kept informed and up to date with regard to the changing situation."^[31]

From the Medscape article:

The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, received a specimen of the H7N9 virus from China yesterday. On April 9, the CDC activated the Emergency Operation Center (EOC) at Level 2 (there are 3 levels, with 1 as the highest) to support the management of the emerging H7N9 situation, Sharon KD Hoskins, MPH, senior press officer at the CDC told Medscape Medical News in an email.

Researchers used real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses to test the patients' respiratory specimens for influenza and other respiratory viruses.

....In an accompanying perspective, Timothy M. Uyeki, MD, MPH, MPP, and Nancy J. Cox, PhD, from the Influenza Division, National Center for Immunization and Respiratory Diseases at the CDC, commented on the article, noting that this outbreak "is of major public health significance."

"The hemagglutinin (HA) sequence data suggest that these H7N9 viruses are a low-pathogenic avian influenza A virus and that infection of wild birds and domestic poultry would therefore result in asymptomatic or mild avian disease, potentially leading to a 'silent' widespread epizootic in China and neighboring countries," Drs. Uyeki and Cox write. The HPAI H5N1 virus usually causes rapid death in infected chickens.

I am not certain, but I am pretty confident that most labs in the United States are currently incapable of subtyping anything other than the prevaling seasonal flus of pH1N1, H3N2, B, and swine H3N2 (nice call, CDC). Anything other than these substrains are lumped into one or more catagories of A: "Subtyping not performed," or A "Unable to subtype."   However, the CDC is also beginning to catalog incidences of other novel influenzas.  From their April 6th report:

Novel Influenza A Virus

No new human infections with novel influenza A viruses in the United States were reported to CDC during week 14.

A total of 312 infections with variant influenza viruses (308 H3N2v viruses, 3 H1N2v viruses, and 1 H1N1v virus) have been reported from 11 states since July 2012. More information about H3N2v infections can be found at http://www.cdc.gov/flu/swineflu/h3n2v-cases.htm.

Assuming few, if any, US labs can currently quickly detect H7N9 bird flu, the only other capability the CDC has is to monitor and initiate surveillance of the public's health.  This means both ramping up a central monitoring presence dealing with day-to-day issues, and also ramping up state health departments to begin watching for unusual spikes in ILI, or Influenza-Like-Illness.

By activating their EOC at level 2, the CDC is able to pull in disparate elements and to begin the process of surveillance in earnest. Things you just cannot do sitting at a desk, you can do in a central coordinating facility, open-air, with people at their posts.  Having been in the State of Florida EOC many times, including pandemic exercises, actual hurricane tracking and the afternoon of 9/11 (and for days afterward), the ability to sort information and make decisions does not happen in a better environment.

On April 2nd, I formally activated the State of Florida CIO Association's Pandemic Committee.  It had stood in informal recess since the Swine Flu pandemic was declared over in 2010.  However, I decided that once the chickens were not doing their duty and dying, we had a real conundrum on our hands!

In fact, just last week, the Florida Department of Health announced that they were beginning monitoring the China H7N9 situation.  I suspect other state health organizations are ramping up, if for no other reason than to give the CDC timely and accurate information, should there be spikes in respiratory illness.

So what would a spike look like?  The spike would look something like this:

  
Hmmm.  This is the actual CDC Pneumonia and Influenza Mortality chart for April 6th, 2013. 

The top black line represents the epidemic threshhold.  The bottom black line represents the seasonal baseline.

The red line represents the actual reported cases.  As you can see, the red line is at the highest point since a spike at the beginning of calendar 2011, six months after the end of the Swine Flu Pandemic. In fact, the chart had suddenly spiked to a level higher than at any point since 2009.

Not sure of what was going on, but knowing this occurred before my rebirth as a flu blogger, I reached out to Mike Coston (again). I asked Mike about what had happened? 

Mike told me that the CDC immediately looked into the situation. In fact, he blogged on both the mortality spike and the CDC's response. Apparently, what happened is that H3N2 drifted.  If you need a primer on antigenic shift vs. antigenic drift, click here.

Anyway, what happened is that, apparently, the H3N2 seasonal flu drifted.  And seniors, who may not have been vaccinated as often as recommended, had no immunity to the drifted virus -- immunity they might have had, if they had goten regular flu shots.  H3N2 is a nasty bug for anyone, but especially for the elderly, who died in numbers sufficient to trigger the uptick that you just saw.

A similar uptick, especially coming now as flu season wanes, would trigger a pretty quick CDC response.  This is why the CDC activated.  This is why state departments of health are getting ready to ramap up their surveillance. 

To recap:

• The chickens are not doing their duty and dying.
• China has no real idea how widespread the virus is.
• Nobody else does, either.
• There is currently no reason to suspect there is H7N9 in North America.
• That having been said, there is always the possibility that infected, asymptomatic travelers have come into the United States via any of the Pacific ports of call and airports. Unlikely, but not impossible.
• Certainly, we would have seen the virus in Hong Kong before we would have seen it here.
• Currently, there is no inexpensive, routine way to test in doctors' offices or public health departments in the USA for H7N9. 
• H7N9 would appear as "Type A, Unable to subtype" or "Type A, subtyping not performed."
• We have a long way to go with this situation.

As of 9:50 AM EDT, China's H7N9 cases have jumped to 38, with 10 deaths. Overnight, five new cases were reported, along with one death.  So we appear to be settling into a bit of a routine here, with a handful of new cases being reported, and an occasional death.

There still are not enough cases to determine a Case Fatality Rate without panicking everyone, but it is clear that this virus is a killer.  The new cases are of people who are very, very sick, and are admitted and tested and confirmed and (hopefully) isolated.

When I worked for an IBM business partner, one of the axioms I learned there was:  You Don't Know What You Don't Know.  And we don't know several things.

First, a Chinese report states that of some 700+ chickens culled at Shanghai wet markets, only 20 tested positive for H7N9. Crawford Killian covers this nicely in his blog, The Silence of the Chickens. You cannot detect what isn't there. Shanghai authorities just took 111,000 birds out of the public diet for a nonexistent problem. Of course, they had to do this:  It is Standard Operating Procedure for killing off a pandemic candidate virus.  See Dr. Margaret Chan's decision in 1997 when a human-to-human H5N1 threatened the entire world in Hong Kong. 

The cases are being found without organizing human testing.  No H7N9 rapid test exists.  Expensive and time-consuming reverse-PCR tests need to know what they are looking for.  Needless to say, H7N9 reagents were the last things anyone was expecting to stock.  So today's press release from the Chinese version of the CDC is welcome news:

Testing reagents for the avian influenza A/H7N9 virus have been distributed by China CDC to all influenza network laboratories of 31 provinces across China. As of 8 April 2013, a total of 160,000 Real-time PCR reagents have been delivered to make all areas capable of detecting human infections with avian influenza A/H7N9 virus.

The Chinese now have the tools necessary to get proactive and get ahead their arms around the scope of this new virus. We simply do not know how many Chinese have been infected; how many have truly died; and how transmissible this virus has become.

Yesterday also brought us the controversial story of Chinese scientists who theorize, in remarkable candidness and lack of censorship, that this new flu may mutate 8 times faster than normal viruses.  THis conclusion was reached by looking at two H7N9 strains spaced some two weeks apart.  Specifically, there were nine changes in the hemagglutinin  over that two-week period.  from this, the scientists concluded the virus was capable of massive, sweeping mutations in a shortened period of time. 

I wonder if our CDC got tipped off on this pending story and that is why they decided the most prudent thing to do was open its EOC at level 2. 

I am also reminded of the forthcoming animated film Epic; specifically, the upcoming trailer.  Click on this link and forward to 2:08.  Perhaps if this virus can mutate so quickly, it can mutate to the life expectancy of this fruit fly?  We can hope so.

UPDATE:  Flutrackers is reporting two Hong Kong residents are being monitored.  This is not new and has already happened.  We should get answers quickly.

The situation over the past two days has pretty much been the same.  New cases, all located in the areas previously identified for H7N9 infection. 

Blessedly, there are those who are looking at the data and coming up with some pretty interesting analysis.  First, I refer you to Mike Coston's blog of today. Titled "Three graphic descriptions of China's H7N9 outbreak," this post collects some great information from informed sources.

The first chart comes from Dr. Ian Mackay.  Dr. Mackay runs a flu blogsite in Australia.  The chart shows the current (as of yesterday, and LOL on the word "Current" right now! I cannot even tell you what the current counts are.) individual H7N9 cases.  As you can see, only seven of the 28 cases had definable, confirmed contact with poultry in wet markets or the actual preparation of fowl.  This is problematic, because it seems to run counter to the prevailing theory that wet markets are the spawning place for H7N9 bird flu. It may suggest adaptation to a different host, mammilian in nature, as Dr. Richard Webby of St. Jude has theorized by looking at the makeup of the virus itself.

We just don't know enough yet on this front.  We assume and can pretty safely state that poultry is or has been a vector.  But the culling of 111,000 birds in Shanghai and adjacent wet markets has yielded little virus. If this cull had yielded virus, I have to believe the Chinese government would have trumpeted this fact and declared the outbreak over.

The second set of charts comes from veteran Flutrackers poster Laidback Al.  Laidback Al is a Jedi Master of the highest order when it comes to charts and maps of bird flu outbreaks.  His analysis and ability to see The Big Picture are impatiently sought and happily received when he weighs in.

His current geospacial analysis can be found at this link. I reproduce one key map below:

Look at the geographic dispersion of human cases.  If this were limited to wet markets, perhaps, we would not see this level of dispersion.  Of course, travel needs to be accounted for. But we are talking a huge area here. There are other charts in Laidback Al's post worth poring over.  The other chart that got my eye was the mortality - versus - morbidity chart. The ratio of deaths to cases, while admittedly a very small sample, shows the virus is killing young adults and the very old.  This seems to fit the mold of pandemic candidate viruses, whose proclivity is toward young adults and the elderly with their assorted contributing ailments.

We must look forward while looking back.  Only testing will determine how widespread H7N9 truly is in China.  A nice place to look would be the downstream rivers, streams and tributaries shown in another Laidback Al map.  Looking at those areas downstream from Shanghai, and matching up those principalities with any unexplained reports of respiratory failure, might prove quite useful.

In the meantime, everyone continues to monitor the developing situation.

The photo accompanaying today's Helen Branswell MetroNews/Canadian Press story regarding H7N9 avian influenza stuck out to me like a sore thumb.

Here's the photo.  Can you tell what set me off?

If you said the cat, you'd be correct.  Cats have a history with bird flu.  In Indonesia, cats became such a worrisome vector that the government actually ordered the testing of cats. For the story, read my blog from 2007.

Also, in 2009, pH1N1 (the virus formerly known as swine flu) infected a housecat.  Not in China; in Iowa.  You can read my blog on that here. and the original Reuters story here.  Wikipedia says:

Felidae (cats)

Domestic cats can get H5N1 from eating birds, and can transmit it to other cats and possibly to people.

"In Bangkok, Thailand, all the cats in one household are known to have died of H5N1 in 2004. Tigers and leopards in Thai zoos also died, while in 2007 two cats near an outbreak in poultry and people in Iraq were confirmed to have died of H5N1, as were three German cats that ate wild birds. In Austria cats were infected but remained healthy". Cats in Indonesia were also found to have been infected with H5N1.^[39]

The spread to more and more types and populations of birds and the ability of felidae (cats) to catch H5N1 from eating this natural prey means the creation of a reservoir for H5N1 in cats where the virus can adapt to mammals is one of the many possible pathways to a pandemic.

[edit] October 2004

Variants have been found in a number of domestic cats, leopards and tigers in Thailand, with high lethality.^[40] "The Thailand Zoo tiger outbreak killed more than 140 tigers, causing health officials to make the decision to cull all the sick tigers in an effort to stop the zoo from becoming a reservoir for H5N1 influenza.^[41][42] A study of domestic cats showed H5N1 virus infection by ingestion of infected poultry and also by contact with other infected cats (Kuiken et al., 2004)."^[43] The initial OIE report reads: "the clinical manifestations began on 11 October 2004 with weakness, lethargy, respiratory distress and high fever (about 41-42 degrees Celsius). There was no response to any antibiotic treatment. Death occurred within three days following the onset of clinical signs with severe pulmonary lesions."^[44]

[edit] February 28, 2006

A dead cat infected with the H5N1 bird flu virus was found in Germany.^[45]

[edit] March 6, 2006

Hans Seitinger, the top agriculture official in the southern state of Styria, Austria announced that several still living cats in Styria have tested positive for H5N1:^[46]

[edit] August 2006

It was announced in the August 2006 CDC EID journal that while literature describing HPAI H5N1 infection in cats had been limited to a subset of clade I viruses; a Qinghai-like virus (they are genetically distinct from other clade II viruses) killed up to five cats and 51 chickens from February 3 to February 5, 2006 in Grd Jotyar (~10 km north of Erbil City, Iraq). Two of the cats were available for examination.

"An influenza A H5 virus was present in multiple organs in all species from the outbreak site in Grd Jotyar (Table). cDNA for sequencing was amplified directly from RNA extracts from pathologic materials without virus isolation. On the basis of sequence analysis of the full HA1 gene and 219 amino acids of the HA2 gene, the viruses from the goose and 1 cat from Grd Jotyar and from the person who died from Sarcapcarn (sequence derived from PCR amplification from first-passage egg material) are >99% identical at the nucleotide and amino acid levels (GenBank nos. DQ435200–02). Thus, no indication of virus adaptation to cats was found. The viruses from Iraq are most closely related to currently circulating Qinghai-like viruses, but when compared with A/bar-headed goose/Qinghai/65/2005 (H5N1) (GenBank no. DQ095622), they share only 97.4% identity at the nucleic acid level with 3 amino acid substitutions of unknown significance. On the other hand, the virus from the cat is only 93.4% identical to A/tiger/Thailand/CU-T4/2004(H5N1) (GenBank no. AY972539). These results are not surprising, given that these strains are representative of different clades (8,9). Sequencing of 1,349 bp of the N gene from cat 1 and the goose (to be submitted to GenBank) show identity at the amino acid level, and that the N genes of viruses infecting the cat and goose are >99% identical to that of A/bar-headed goose/Qinghai/65/2005(H5N1). These findings support the notion that cats may be broadly susceptible to circulating H5N1 viruses and thus may play a role in reassortment, antigenic drift, and transmission."^[47]

[edit] January 24, 2007

"Chairul Anwar Nidom of Airlangga University in Surabaya, Indonesia, told journalists last week that he had taken blood samples from 500 stray cats near poultry markets in four areas of Java, including the capital, Jakarta, and one area in Sumatra, all of which have recently had outbreaks of H5N1 in poultry and people. Of these cats, 20% carried antibodies to H5N1. This does not mean that they were still carrying the virus, only that they had been infected - probably through eating birds that had H5N1. Many other cats that were infected are likely to have died from the resulting illness, so many more than 20% of the original cat populations may have acquired H5N1."^[39]

Seeing a cat sitting outside an empty stall remined me immediately of these issues. Are the Chinese testing the cats? Are we seeing the death of cats in any significant number?  Are the Chinese doing surveillance with veterinarians? 

Cats eating wild birds is one thing.  Cats eating diseased fowl in wet markets is another.  Where are we more likely to see this?

Dr. Henry Niman may have stumbled onto something interesting.  In his Recombinomics commentary of Saturday, he has identified a cash settlement from the hospital treating the first known H7N9 patients. 

Dr. Niman cited an article from the South China Morning Post.  Here's the headline and some copy: