What's up in Hamburg?

I am pulling this directly from the proMED (Harvard) report.  No claim of authorship from this corner!

UNDIAGNOSED ILLNESS - GERMANY: (HAMBURG) RESPIRATORY, FATAL, REQUEST FOR INFORMATION

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A ProMED-mail post

<http://www.promedmail.org>

ProMED-mail is a program of the

International Society for Infectious Diseases <http://www.isid.org>

Date: Wed 10 Apr 2013

Source: Bild [in German, machine trans., edited] <http://www.bild.de/regional/hamburg/viren/toetet-polizisten-im-uke-29943928.bild.html>

A 49 year old policeman is dead, 5 other persons are ill and doctors are puzzled by this mysterious disease just outside of Hamburg.

Andreas Breitner, Minister of the Interior, confirmed to the "Schleswig Holstein newspaper" the death of the 49-year-old policeman at the University Medical Center Hamburg-Eppendorf (UKE) on Tuesday [9 Apr 2013], after multi-organ failure.

Another policeman, aged 38 years is in critical condition. He is suffering from similar flu symptoms, including severe pneumonia.

A teacher from the Schacht Audorf area near Rendsburg has also died of multi-organ failure in the UKE, and according to unconfirmed reports,

3 other persons from the same region are seriously ill.

All are suffering from flu-like symptoms but the doctors do not know what disease is affecting them. It could be a "degenerated virus"

[?mutated], the "Schleswig Holstein" newspaper reporter quotes" an official.

District spokesperson Martin Schmedtje said: "Both policemen showed the same clinical picture. However, we do not know yet whether there is a pathogen or whether a pathogen was actually the cause."

After investigation there are no known connections between both colleagues.

Police spokesperson Sonke Hinrichs said, "the 2 policemen did not work in the same agency, were not on duty together, do not live in the same place. There is no visible connection, but naturally we are working together to try to find out what has happened."

The hospital is also investigating a possible link. UKE spokesperson Christine Jaehn said, "At present no patients with unusual infectious diseases are being treated in the UKE intensive care unit. Moreover, no accumulation of patients exists in the Rendsburg area."

Public health authorities in Rendsburg-Eckernfoerde have been activated since Friday [5 Apr 2013].

But so far nobody knows what this deadly disease is. On Wednesday evening [10 Apr 2013] the Rendsburg-Eckernfoerde District Administrator announced, " Despite the efforts of the specialists involved we have not been able to identify a pathogen."

However, the danger has been estimated as low. District spokesman Martin Schmedtje said, "a recommendation from the health services to close public facilities as a precaution is not necessary. General hygiene measures taken in times of rampant influenza, are sufficient."

Communicated by:

ProMED-mail

<promed@promedmail.org>

[Given the heightened awareness of the public and public health community for severe acute respiratory illness (SARI) and the identification of 2 new novel organisms producing SARI -- the novel coronavirus (nCoV) identified in individuals with contact with Middle Eastern countries and the appearance of human cases of influenza H7N9, an avian influenza virus in Eastern China, a report such as the one above is potentially cause for concern. Other reports on this occurrence in Germany have been posted on FluTrackers

(<http://www.flutrackers.com>) where there is mention that the fatality referred to in the newswire above was found to be attributable to influenza, but a specific virus was not mentioned (?H1N1, H3N2).

As there is no history of travel outside of Germany, the likelihood of this being due to infection with either the nCoV or the avian influenza H7N9 is very low. More information on the results of laboratory studies and other investigations would be greatly appreciated.

Rendsburg-Eckernfoerde is a district in Schleswig-Holstein, Germany.

It is bordered by (from the east and clockwise) the city of Kiel, the district of Ploen, the city of Neumuenster, the districts of Segeberg, Steinburg, Dithmarschen, and Schleswig-Flensburg, and the Baltic Sea (see <http://en.wikipedia.org/wiki/Rendsburg-Eckernf%C3%B6rde> for a map and additional information on the District).

OK, now my biting, insightful commentary.

I called Mike Coston yesterday.  Mike is FLA_MEDIC and the founder of the well-known and respected Avian Flu Diary blog. He is a buddy and it is great talking with him again. Anyway, I asked him if I could interrupt his blogging for a few minutes.  He only wrote ten or so blogs yesterday (slacker!) and only writers and bloggers know how painful deadlines can truly be.

Anyway, Mike told me about this story, and I was very interested to see the proMED journal about it. Hamburg recently struggled with an outbreak of H5N3 in poultry, and it does rest on the Baltic. 

It is now five days later, and we still have no explanation as to what has infected these individuals.  I find that interesting, because if a simple explanation had been found, more than enough time has passed to tell everyone.  One has to assume the German press remains interested in this case.  Whether it is related to H7N9, NCoV, or even H5N1 is both unknown and wrong to speculate upon until answers come.

April 11, 2013: 38 H7N9 cases, ten deaths.  

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.

Pausing to look at the data on H7N9 infections

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.

image

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:

Name:  H7N9 China cases 20130409 dots.jpg Views: 306 Size:  119.4 KB

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.

A picture is worth a thousand words. Or nine lives. Or something like that. 

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 hereWikipedia 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?

H7N9 bird flu update: 24 confirmed cases, 7 deaths. And Zhong weighs in.

Today's count: There are now 24 confirmed cases of human H7N9, with seven deaths.  ALl the cases and all the deaths remain in and around Shanghai and its immediately adjacent provinces. 

Veteran flu blogger and noted author Crawford Killian has also posted a story regarding Zhong Nanshan. Zhong, if you have forgotten, became somewhat of a national hero in China m(and around the world, among medical experts) for his courageous stand against the status quo with SARS in 2003. He battled not just the virus, but inept local ChiCom government bureaucrats who stymied his initial attempts at transparency. I refer you to one of my 2008 blogs for background.

Zhong is arguing for a much larger surveillance effort than is currently underway.  His remarks echo those of the Bill and Melinda Gates Foundation, which I covered last week. 

From Crof's blog. 

Zhong Nanshan, Chinese Academy of Engineering, said, "Analysis shows that the H7N9 virus comes from fowl, including poultry, wild fowl migrating birds and pigeons. We should expand the range of screening as not so many people have direct contact with poultry." 

I wonder if Zhong means "not so many people (who contracted this virus) have direct contact with poultry."