gisaid

Recombinomics Commentary 19:40
October 4, 2011
The latest series of trH3N2 and trH1N2 swine sequences from 2011 (released at Genbank by Iowa State University) provide additional insight into the evolution of the new human contagion, trH3N2. Although the new swine sequences have key components of the 2011 trH3N2 reported in Indiana (A/Indiana/08/2011), and the Washington County fair in western Pennsylvania (A/Pennsylvania/09/2011, A/Pennsylvania/10/2011, A/Pennsylvania/11/2011), the swine isolates fail to match the constellation of genes fund in all four human cases, providing additional evidence for the emergence of a new human contagion, trH3N2, and another influenza pandemic.
 
The 2011 trH3N2 human sequences extended the spread of the 2010 human trH3N2 sequences by retaining 5 of the 8 gene segments. The new contagion has swapped out the other three gene segments, PB1, NA, MP for genes found in earlier human triple reassortants (trH1N1, trH3N2, pandemic H1N1), to create a new human contagion, trH3N2, that can efficiently transmit in humans. As has been mentioned by the CDC and WHO, the 2011 human trH3N2 sequences have acquired a pandemic H1N1 M gene segment, which is critical for the efficient transmission of pandemic H1N1 between humans.

However, the human trH3N2 sequences have also acquired the N2 that was in one of the 2010 Pennsylvania cases, A/Pennsylvania/14/2010, as well as a PB1 more closely related to sequences from the Huron County fair (A/Ohio/01/2007 and A/Ohio/02/2007) and this new constellation of genes was in all four 2011 human trH3N2 cases reported to date, and not in any of the reported swine sequences, including the recently released sequences (trH3N2 and trH1N2) from 2010 and 2011.
 
The recently released 2011 swine sequences had information on HA, NA, and MP, but this limited sub-set failed to match the human trH3N2 constellation.  In 2010 there were H1N2 sequences (including A/swine/Minnesota/A01047604/2010 and A/swine/South Dakota/4/2010) with a pandemic H1N1 M gene and an N2 that matched the recent human trH3N2 sequences.  However, a more complete analysis of the Minnesota sequence showed that all six internal genes matched pandemic H1N1, and other such sequences (all six pandemic H1n1 internal genes wrapped in H and N from other triple reassortants) have been widely reported in swine, but not in humans.  Therefore, it is likely that the recent H1N2 swine sequences (including A/swine/Minnesota/A01049956/2011, A/swine/Iowa/A01049723/2011, A/swine/Iowa/A01049728/2011, A/swine/Indiana/A01049964/2011, A/swine/Illinois/A01049871/2011, A/swine/Illinois/A01049872/2011, A/swine/Iowa/A01049887/2011, A/swine/Iowa/A01049722/2011) have a similar constellation (as well as a different serotype). 
 
Other recent trH3N2 isolates (including A/swine/Texas/A01049555/2011, A/swine/Texas/A01049556/2011, A/swine/Indiana/A01049750/2011, A/swine/Texas/A01049914/2011, A/swine/Texas/A01049915/2011) have a pandemic M gene segment, but different H3 and N2.  Similarly, recent isolates have a matching H3 and N2 (including A/swine/Indiana/A01049744/2011, A/swine/Indiana/A01049745/2011, A/swine/North Carolina/A01049436/2011, A/swine/Indiana/A01049653/2011, A/swine/Indiana/A0109091/2010) but have an M gene related to the 2010 trH3N2 isolates.  
 
Thus, even though the surveillance of 2010 and 2011 swine has increased (including one sequence from July, 2011), none of the public sequences match the 2011 human trH3N2 constellation, strongly suggesting that this new pathogen is transmitting in humans.
 
The number of human cases has been limited, but all four 2011 isolates have the same constellation of genes including a pandemic H1N1 M gene, which is critical for human to human transmission. Moreover, three of the four sequences are virtually identical, but isolated from distinct locations, including the Indiana case with no swine contact.  Moreover, none of the four cases were epidemiologically linked, indicating each infection was independent. 
 
The matching of all four human cases, in the absence of any matches with swine isolates signals an adaptation and spread of this trH3N2 contagion with a novel constellation of flu genes.
The limited testing of H3N2 cases, and the focus on patients with links to swine, continues to raise pandemic concerns.

Remember the flu pandemic?

The one that swept the world just two years ago? You might be forgiven if this has slipped your mind – after all, it doesn’t seem like such a big deal now. That’s because we got lucky: despite many dire warnings about the danger of another 1918 “Spanish flu”, when the 2009 pandemic arrived, it was far milder than previous pandemics. Hundreds of millions of people got the flu in 2009, but for most of them, it wasn’t so bad. In fact, the new flu is less severe the old flu – the strain that was circulating before the new pandemic hit.

Now we have two flus circulating: the “old” H3N2, and the 2009 pandemic flu, called H1N1. (And the vaccine protects against both of them, so get your flu shot! Your friends, neighbors, and co-workers will all benefit.)

We really dodged a bullet in 2009. Despite our best efforts, it took 7 months (April to November) before a new vaccine was ready. Before we realized how mild it was, people were desperately snapping up stores of Tamiflu, an anti-viral medicine that only barely helps to treat the flu. If it had been like 1918, Tamiflu wouldn’t have helped much, and tens of millions would have died.

The 2009 pandemic originated in pig farms in Mexico. We don’t know precisely where it made the first leap into humans, but it appears that two different strains joined together in a pig somewhere to create the new H1N1. The flu has a nasty habit of jumping the species barrier, hopping to humans from both pigs and chickens.

So now that we know all this, next time will be different, right? The world’s influenza scientists are monitoring pigs and chickens closely now, keeping a close eye on any new flu strains. Right? RIGHT???

Er, no. Not exactly. For one thing, surveillance in pigs appears to be nonexistent. I checked to see how many flu sequences from pigs in Mexican have been desposited in the public archive at GenBank since 2009 (using this terrific database). The result? One, in 2009. Nothing from 2010 or 2011. Hello, is anyone awake at the CDC and the WHO?

This despite the fact that scientists have serious concerns that the deadly H5N1 avian flu (the “bird flu”) could combine its genes with H1N1 and create a really nasty new flu strain. And scientists have long had concerns that pigs could be the mixing vessels for new flu outbreaks – exactly what happened in 2009.

But wait… maybe they are monitoring the flu, but they’re just not telling us. That would feed into all the fringe government conspiracy groups that claimed the 2009 pandemic was an intentionally engineered government-funded enterprise (see this BMJ article for more). I don’t believe any of those conspiracy theories – most of them are just nuts – but read on.

Sharing data about flu viruses has been a touchy subject with the WHO and the CDC for years. As reported by the University of Minnesota’s CIDRAP:

“In late 2006, virus sharing became an international flash point when Indonesia broke a long tradition of free international sharing of flu virus specimens by withholding its H5N1 virus samples as a protest against the high cost of commercial vaccines derived from such samples. The controversy has drawn attention to the problem of equitably distributing vaccines in the event of a pandemic.”

A few months ago, the WHO finally agreed on a new set of principles on data sharing, which states that

“The WHO GISRS laboratories [which includes the CDC] will submit genetic sequences data to GISAID and Genbank or similar databases in a timely manner.”

Excellent!  So are they doing it?

As every biomedical scientist knows, GenBank is a free, public database of genetic sequence data that contains millions of sequences, from humans, bacteria, viruses, you name it. But GISAID is a Swiss database – one that I initially supported – just for flu data. The original mission of GISAID was that data deposited there would go to GenBank as well, with little or no delay. But in a classic bait-and-switch move, the GISAID board changed that policy after the database was up and running, and now they can sit on data as long as they want.

OK, it’s a private database, so they can do what they want. True enough. But here’s the surprising bit: the CDC deposits most of its flu sequences ONLY in GISAID, where they can milk them for scientific results for years without sharing them with others. As one of GISAID’s original supporters, I have an account there, and here’s what I found.

So far, the CDC has deposited sequences from 6,801 flu isolates in GISAID, of which only a tiny handful are in GenBank. 3201 of these originated in the U.S., so there can’t be any foreign government insisting that they be kept secret. These provide critical data that could help scientists predict what is coming in the next flu season. But you can’t get these sequences without a GISAID account. And even if you have a GISAID account, as I do, you have to agree not to release the data as a condition of getting a look.

So why does the CDC deposit sequences in GISAID? I think it’s precisely because of the restrictions. CDC’s scientists don’t want others to look at “their” data, because they’re afraid someone else might discover something important and publish it before them.

The CDC, of course, is part of the U.S. government, and all its work is funded by the public. But it seems that the CDC flu scientists have forgotten their public health mission – or at least, they appear to be more concerned about their own careers (and the papers they might publish) than about making sure the world is ready for the next pandemic.

And by the way, even these sequences don’t seem to include anything from pigs in Mexico. Hello, CDC? You are looking at swine flu now, aren’t you?

Perhaps I’m being a bit harsh. I love the CDC: they do a terrific job most of the time, providing vital services to protect the public from infectious diseases. But their internal scientists sometimes seem to operate within a cocoon, and I’m afraid that’s happening here. This culture of secrecy has got to stop, and I suspect that will only happen under pressure from the outside. The CDC Director, Thomas Frieden, needs to tell his flu people to start sharing what they know with the rest of the world. And they can start by putting their data in GenBank.

http://www.forbes.com/sites/stevensalzberg/2011/10/02/is-the-government-hiding-something-about-swine-flu/