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Week 7 of the March-May H7N9 outbreak ends.

And it would seem that the current outbreak as a whole is largely over as well. Without specific details its hard to place when the 1 new case and 4 deaths (among existing positives) occurred that were announced earlier this week in the official update from China. My own weekly numbering is from the 31st when the WHO was notified, which is slightly off kilter with the weekly report dates from China. So what can I comment on? Well, 2 provinces (Shandong and Jiangsu) and a municipality (Shanghai) have wound down the level of their emergency response. No new cases there for some time.

So we're left wondering what sparked this strange spread of human infection with a virus that is almost identical in its HA gene sequence from that found in birds and the environment during the outbreak (>99.5% amino acid identity; about 88% with H7N9s found in the US and Guatemala years earlier). 

The strangest part is if it spread from birds.....why weren't vendors, traders, butchers and truckers in the closest of contact with the suspected hosts more commonly infected and reporting to hospital? Are they just too young? Too healthy? H7N9 infection seems to lead to severe disease most of the time. Did they have specific or cross-reactive immunity? Was the underlying disease factor the most significant issues for severe illness? We read in the literature that contacts mostly had no severe disease.

I guess we now wait to see what wild bird testing yields. Could wild bird populations already have H7N9 in them and be circulating in the Mediterranean and Australasian flyways?
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First ever horse infection with Australian bat lyssavirus (ABLV).

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Having killed the 3 humans its infected since it was first isolated in 1996, the first recorded case of ABLV in a horse in the state of Queensland, Australia has been quickly acted upon.

Humans in contact with a horse that was put down last Saturday (11.05.13)have been offered treatment after test results on Friday 17.05.13 identified ABLV. There are 20 other horses on the property. This was the second horse euthanased from the same property although the first horse was not subjected to any testing. ABLV, 1 of 12 species of the genus Lyssavirus, family Rhabdoviridae, has been found in several bat species.

Rabies immunoglobulin can halt severe disease along with a course of rabies vaccine infections
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Haemagglutinin cleavage site graphic.

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I've added a new graphic to the H7N9 page that compares the important cleavage site in the immature HA protein among influenza A viruses, including H7N9. 

This shows that H7N9 is more similar to seasonal influenza viruses in this area-low-pathogenic viruses rather than high pathogenic viruses. 

The latter have a multiple basic amino acids at the cleavage site making them a target for proteases located throughout the body rather than just in the human respiratory system and bird gut.
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Media MER muttering more than murmurs.

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Ouch. Anyway, before you finish typing or reading that coronavirus outbreak story make sure it doesn't use the names human betacoronavirus 2c EMC, human betacoronavirus 2c England-Qatar, human betacoronavirus 2C Jordan-N3, betacoronavirus England 1 or (especially the short-sighted) novel coronavirus (NCoV)-they are so, like, yesterday's name. 

Prof Raoul J. de Groot and a host of coronavirus (CoV) experts, comprising the CoV Study Group, have penned a scientific article that has just been accepted into the Journal of Virology. The name of the newest spiky little killer is officially Middle East respiratory syndrome coronavirus or MERS-CoV for short. New variants (the same virus detected in other people/animals) will be given a name using the influenza virus naming system:

Virus name host/country of virus detection/variant identifier/year detected e.g. MERS-CoV Hu/Jordan-N3/2012).

That's as official as it gets anyway so this is how we should label it from here on in.

We're also avoiding calling it a human CoV until we know how humans get the infections. Since the virus is similar to a bat version one of many question is whether the cases all got it directly from bats (unlikely) or from human contact with another, intermediate, host. This builds on the media reports noted on 07.05.13.
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41 HCoV-EMC Cases.

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The numbers rise again and "foreign specialists" have been hired (?perhaps invited) to help the Kingdom contain the spread of MERS-CoV.

While human-to-human transmission is very likely occurring, sustained transmission that is, infection going beyond the immediate close contact, to their contacts and so on, is not. See the figure - circles represent a person; yellow represents spread beyond immediate and close contacts.MERS-CoV transmission seems to be limited to close contact and perhaps long exposure.
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Editor's Note #5.

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I thought I might add a new bit to this bloggy thing I'm doing (6 weeks old and I'm changing it already). 

So, see below for the first "Stuff from the Literature" comment. I'll try and find a paper or two and break it into manageable chunks. 

As always, this is firstly an effort by me to learn something new, and secondly to try and communicate that to others. It won't be definably regular.
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Stuff from the literature: Dabbling ducks respond to flu viruses.

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Yes, ducks do mount an immune response even to "low path" influenza virus infections. Dabbling ducks (those that feed near the surface rather than diving underwater) are the natural reservoir for Low Pathogenic Avian Influenza (LPAI).

LPAI viruses circulate among wild birds, especially Mallards, all the time. As Jourdain and colleagues pointed out in 2010, mallards are not obviously affected by experimental infection - for example they don't lose weight or cease moving around and they don't show any other clear signs of disease (very slight temperature rise for 2-days) after infection. However, the authors note other studies identifying egg production problems and also the importance of further studies on wild populations as opposed to a small number of birds.

Perkins and colleagues showed that ducks, sparrows and gulls tend to control virus replication differently from chickens suggesting that the ducks may have a better ability to mount an immune response. A weaker (less antibody and shedding)reinfection with the same H7N7 virus was still possible even in the presence of an antibody response to the first H7N7 infection. Reinfection by a different virus subtype (H5N2) seems to have been blocked by the antibodies made to initial infection by H7N7; so-called heterotypic immunity (cross-protective immunity to a different viral subtype).

Volmer and colleagues reported in 2011 that ducks infected with an LPAI mount an interferon (IFN) response in their guts. The cells (enterocytes) of the duck gut is where most flu virus replication occurs and its from here that most of the virus shedding originates. This study found the gut was inflamed and that there was some cell death. So, not at all like the respiratory disease the human host experiences. In the cells lining the intestine, the authors found lots of myxovirus-resistant (Mx) gene activity; diverse genes in birds, which may be especially well adapted in mallards to control influenza, that are key to the earliest immune response to virus infections (also important in humans) and particularly effective against influenza virus. Mx proteins trap and redirect flu virus nucleoproteins.

In particular, a Type I (antiviral) IFN response was detected. IFN-g (gamma) gene activity was up, activating important immune cells (T cells or natural killer cells), important for flu vaccines in poultry and humans.

Swayne provides an excellent review of the vaccines used in birds to moderate H5N1 disease ('fowl plague'). The formulation, use and effect of these vaccines are as varied as the influenza viruses themselves. China leads the field in the use of reverse genetics to create the contemporary flu viruses carrying the most relevant immune stimulating (antigenic) bits.
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MERS - clear as mud.

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Reports suggest 19-20 deaths now with 2 new cases, both healthcare workers, reported by the Saudi Ministry of Health. 

They release notes that "citizens, journalists and interested" can get information from the MOH website which is updated "first hand". 

Unfortunately the translator can't translate fixed graphics written in Arabic and used liberally through out the site, so look to click on the pretty coronavirus icon if you want to be updated and then go to the press releases. 

Apparently the translator also has some issues with Arabic numbers...or else the press reports are from 1434.[UPDATE 16.05: Please pardon my ignorance of the Islamic calendar. As DG has pointed out to me this morning, it is indeed the Hirji year (AH-anno hegirae) of 1434, part of what the Gregorian/Western/Christian calendar calls 2013. No offence was intended.]
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H7N9: the stealth bomber virus.

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As described by EpiVax Inc. previously and now described in a scientific paper in Human Vaccine and Immunotherapeutics, the H7N9 virus is not just stealthy in poultry, its also hard to find in humans. There is concern over whether it will be possible to produce a vaccine that will be effective against a virus with such low predicted immunogenic potential. 

An H7N9 vaccine, without the right concoction of boosting additives, is predicted to be a poor trigger of our immune system's response to it. This is because H7N9 doesn't have as many T cell epitopes as other flu viruses...these are the bits recognized by important white blood cells that fight infection and shorten disease. Because of this human 'stealth' capability, it may evade the human response. 

This has obvious implications for disease (more severe if the host cannot shut the virus down quickly) and may also have implications for the usefulness of existing serodiagnostic (virus-specific antibody-detecting) assays.
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Welcome to Week 7 of the H7N9 outbreak.

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Week 6 was relatively quiet although more fatalities occurred than in Week 5 (3 vs. 2).

No new H7N9 cases with a date of onset in Week 6 occurred, and there were only 3 in Week 5 so confirmed case reports have dropped right back. Tomorrow is "tell-all Tuesday" (well, I'd like some more date data this time around) in which we hope to get a snapshot of cases over the past reporting week in China. No sustained human-to-human transmission, no new provinces or municipalities reporting cases. Reports suggest that with summer coming H7N9 cases will drop off. I'm not convinced given of that H1N1pdm 2009 peaked in the US during the warmer months - I think an emerging flu virus may well be able to buck the trend of seasonality. However, I suspect that seasonality is heavily influenced by virus:virus interactions in the community so it may depend on what other respiratory viruses are co-circulating now and in the coming weeks.
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Matrix-targeted real-time PCR for H7N9.

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A belated congratulations to my fellow Group Leader here at the Qpid lab, A.Prof David Whiley on the implementation and media coverage of his sensitive real-time RT-PCR to detect H7N9 for implementation by Pathology Queensland's microbiology laboratory. 

It targets the matrix gene segment, which as far as we know, is unique among the H7N9 assays in use to date.
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