US CDC testing retrospectively for MERS in Jordan.

I'm little slow on this day old story. Jordan was the site of the first MERS-CoV cases, confirmed retrospectively by NAMRU-3 (see MERS page; Cluster #1). 

The US CDC has been sent 124 samples by the Jordan Ministry of Health from around that time to help further investigate the source of the (as far as we know) first outbreak. 

The 2 cases that had been confirmed were healthcare workers, including an intensive care unit nurse. This strongly suggests at least 1 patient with the unexplained pneumonia occurring in Jordan around April 2012, was a source of the MERS-CoV.
Raises the question of what Hajj 2012 serum samples would reveal?

Moroccan MERS?

ProMED says a news report has been confirmed by the head of the Moroccan Health Defense Network. 

However, FluTrackers has a report that this has been denied by the Moroccan Health Ministry and that samples from the UAE national showing relevant clinical features, were negative for MERS-CoV.

Poultry workers had no prior exposure to H7N9 [UPDATED]

Bai and colleagues report in NEJM that 1,544 samples collected from young adult poultry workers between Jan-Nov 2012 in 4 key provinces/municipalities of China (municipality of Shanghai, Zhejiang province, Jiangsu province and Anhui province) were tested using a haemagglutinin-inhibition (HAI) assay and a microneutralization (MN) assay. 

The HAI assay found some weak reactivity (antibody was positive when diluted as far as 1:40), but no neutralizing antibodies were found by MN test. 

This is chapter 1 of a story that next needs to include more contemporary testing. 

The first part reveals no assay-specific antibodies present in these close contacts of poultry, prior to late 2012; before the H7N9 outbreak.

Nothing unusual about MTAs-are commenters just confused?

Material transfer agreements are more the norm than the exception among scientist used to local an d international collaborations whether working with exotic new viruses - or endemic seasonal viruses from the recent or distant past. 

An article in Science's ScienceInsider goes into more detail about the recent fracas. Perhaps some just don't understand the difference between MTAs, IP, business and public health needs?

It's worth noting that even if I wanted a sample of a common cold virus stored more than 50 years ago and now housed and maintained in one of the world's leading biological banks of such samples, I would have to sign an MTA that imposes restrictions on its downstream use. You can read the whole thing here...one excerpt....

ATCC Material and Progeny: ATCC Material and Progeny may only be used by Purchasers Investigator for research purposes and only in Investigators laboratory.

5 new MERS-CoV cases come from nowhere.

The Saudi Ministry of Health effusive detail below..

Within the framework of the epidemiological surveillance of the novel Coronavirus (MERS-CoV), the Ministry of Health (MOH) has announced that five novel Coronavirus cases have been recorded among citizens in the Eastern Region, ranging in age from 73 to 85 years, but they have all chronic diseases.

That's not an excerpt. That's all of it. Even Coulson wouldn't be that reserved.

Imported French MERS case dies.

Reuters reports that the 65M who contracted MERS-CoV while travelling in Dubai has died. 

He shared a room with a 50M who subsequently contracted the virus and remains in hospital. With the new case above, the case fatality rate sits to 47%.

H7N9 in Beijing.

Busy night. According to crofsblogs and Avian Flu Diary, Beijing has reported a new case of H7N9 in a 6M, confirmed 28.05.13. This makes 133 cases and 37 deaths-3 in Beijing when including an asymptomatic lab confirmation.
This case comes after Beijing rolled H7N9 into its normal influenza virus laboratory testing system and one of China's leading respiratory virus researchers noted the need to remain vigilant about H7N9.

H7N9: airborne transmission not at pandemic levels - infects upper & lower airways, lymph nodes and brain in ferrets.

In a collaborative effort published last week in Science, researchers from China, Canada and the US infected ferrets with a human H7N9 isolate (A/Shanghai/2/2013; "SH2"). The aim was to understand infection, transmission and pathogenicity due to the virus in the main mammalian model for such studies.

Ferrets showed upper respiratory tract disease, similar to that due to influenza A(H1N1)pdm 2009 virus infection, with shedding beginning the day after nasal inoculation - preceding any signs of disease. Obvious ramifications for stealthy spread of virus in this prodromal phase

Infected ferrets housed in the same cage as a non-infected ferret (introduced 24-hours after the the infection of the first occupants) easily transmitted SH2 to the newcomer who showed signs of illness within 36-hours; the same time at which lung inflammation and virus replication in nasal, tracheal, bronchiolar, lymph node and brain tissues was occurring. All these ferrets produced a diagnostic rise in antibodies by 14 days (They seroconverted).

An uninfected ferret in a downwind cage, separated by 10cm, acquired and shed SH2 at 36-hours after exposure (1 animal in 3 experiments). This ferret and one other seroconverted at 14 days post-exposure.

Airborne transmission was therefore possible in two-thirds of exposures in these experiments. H1N1pdm 2009 infected ferrets all shed virus regardless of route of infection confirming practically that H7N9 has some way to go to spread on a par with a known pandemic influenza virus.

Pigs also supported H7N9 infection showing signs and symptoms of disease 0.5 days after virus load was measurable. Direct contact H7N9 transmission was possible with an antibody rise occurring in 25% (1 of 4) of pigs but no virus shedding. No airborne transmission was detectable in the pigs. H1N1pdm 2009 virus was spread efficiently by direct and airborne routes in pigs.

Perhaps pigs are not the universal intermediary mixing vessel they are made out to be - being more susceptible to humanised influenza viruses than those closer to their avian hosts?

No new H7N9 cases for 2nd week.

Self explanatory., There was on death in the week spanning 20.05 to 27.05. 76 cases have recovered now and 37 died. The numbers I'm able to update (once again there are not details) are on the H7N9 page.

EV-A71 in cases of Acute Flaccid Paralysis (AFP), Australia.

ProMED describes a report from researchers at the Australian National Enterovirus Reference Laboratory on 5 cases of AFP positive for EV-A71 between Jan-May 2013. The viruses, found in stool samples from ill children, were identified as belonging to the more virulent genogroup, C4a, by VP1 sequencing.

Members of genogroup C4 were described by van der Sanden and colleagues as being restricted to epidemics in the Asian Pacific region.

Questions about MERS, MTAs and mistakes.

Edited by Dr. Katherine E. Arden

This is a story that stretches back to June 2012-nearly 12 months ago. That's when virologist Prof Ali Mohamed Zaki reportedly notified (or not, depending on the article) the Saudi Arabian Ministry of Health about a fatal case of severe acute respiratory infection in a 60-year old man for which the standard laboratory tests yielded no answers. He sent a sample to researchers at the Erasmus Medical Center (EMC) and followed that up with more testing. He and the Dutch researchers found a new coronavirus (CoV). What seems to be missing from this process was any formal release of that sample by the Saudi Arabian Ministry of Health (MOH). Prof Zaki's ethical position could be seen as murky at best.

On September 20th, an eMail Prof Zaki sent to ProMED was published notifying the world of his process (including how he detected the virus using PCR and grew the virus in culture-processes he conducted while working in Saudi Arabia) and his findings.ProMED was subsequently dressed down by Deputy Minister for Saudi Arabian Public Health, Prof Ziad Memish for publishing the eMail about which the Ministry was unaware. Prof Zaki signed off his eMail from the Dr Fakeeh hospital Jeddah Saudi Arabia, a private hospital.

Prof Zaki's eMail served as a trigger for the testing of another ill male from Qatar who had been airlifted to the UK September 12th - that test yielded the second case of the novel coronavirus.

If Prof Zaki did not follow protocol and sent a specimen without the knowledge or permission of the Kingdom it is interesting, in light of the expected harsh consequences, to speculate on his reasons for doing so. Did Prof Zaki have the supervisory and ethical approval to send a clinical sample out of the country? Did the EMC challenge him on this before accepting the sample(s)? Had Zaki taken the approved steps (if he did not, that is) to notify his superiors and request permission to send a specimen for further characterisation, would he have received timely permission? Would he ever have received permission?

As a result of this situation, an article was published this week that, although lacking in clarity due to machine translation issues, vilifies Prof Zaki for his actions.WHO spokesperson Gregory Hartl was quoted during September 2012 as saying that the coronavirus "is now an international issue"; a comment that raises some questions in light of this latest article about Prof Zaki's actions. Some have expressed frustrationin recent days about the slow provision of information on new MERS-CoV cases. Would the new coronavirus have been made into an international issue if not for the actions of Prof Zaki? Is the Kingdom capable of characterizing a novel CoV? If the Kingdom did proceed with announcing the MERS-CoV and inviting international experts to advise, would it have done so in time to precede one of the most successful hajj gatherings ever? Nearly 4 million pilgrims attended that gathering in 2012. A real concern exists that cases of this unknown virus could disseminate globally because of just such a gathering. That did not happen but at the time no-one could be sure it wouldn't - the risk was evident and remains so for the coming hajj.

Also this week another cause for argument arose when National Microbiology Laboratory researchers in Canada stated that they were not allowed to pass on samples of the MERS-CoV to other laboratories (40 labs have received the virus from the Erasmus researchers to date). This restriction was stipulated in the Material Transfer Agreement (MTA) that accompanied the sample from the Dutch researchers at Erasmus Medical Center (who characterized HCoV-EMC, now known as the MERS-CoV). The comment that China "gave away" H7N9 samples has been used as an example of a better way to conduct collaborative research on emerging pathogens.

MTAs are a pain in the neck. They slow things down. They are not necessarily crafted by the researchers themselves but by the legal advisory team and administrators to protect new knowledge and discoveries. They can also manage and record where and to whom a putative pathogen is sent and what is done with it by the recipient. Is that a bad thing? MTAs are not uncommon in science. They protect many things. Yes, they can protect intellectual property-with the potential to make some money. Good luck with that - there are as many scientists who have found riches in this endeavor as there are Tony Starks and Bruce Waynes.In this case the MTA, among other things, reportedly limits the distribution of what iscurrently a virus with a case fatality rate of 50%. That sort of virus needs to be worked with by experts using expert facilities with suitable restrictions and pre-existing ethical, genetic manipulation and biocontainment standards in place. We observed the uproar among scientists recently when a recombinant influenza pathogen that had the (unproven) potential to be as lethal was created in secure laboratory environment.

Why has no such uproar accompanied the shipping of observably lethal viruses around the world in the absence of MTAs and tighter restrictions?

If other labs would like the virus, they can also apply to the lab that has gone to the effort to detect, characterize, isolate, grow, purify and store it - just as the NML did. The US CDC noted similar caveats on sharing MERS-CoV were put upon it by the UK laboratory that provided it with samples, presumably form the Qatar case.How long will the attacks on Prof Zaki continue? Hard to know. He is no longer working for the Kingdom. Is losing one's job enough punishment for his putative protocol breach?

It is encouraging to read that samples from various potential animals will be sent to researchers in the US who have the expertise to conduct the studies necessary to track down a possible host.

The first human case of MERS-CoV was in June 2012 - it's now May 26th 2013.

Patenting MERS-CoV: no hindrance to diagnosis at all.

Edited by Dr. Katherine E. Arden

This is not the first newly identified virus that researchers at Erasmus, or elsewhere, have patented.

They did the same for human metapneumovirus (HMPV; an endemic respiratory virus and kin to respiratory syncytial virus) after describing its discovery and characterization in 2001.
Another broad-ranging patent also listed on Google is for the human coronavirus (HCoV) NL63, discovered in 2004 by other researchers. Patenting is part of business and today a portion of science research requires proof of the ability of researchers to work with business to help produce real outcomes. Mass-produced diagnostic kits are one outcome - they are made to high standards of quality and distributed worldwide. Research scientists can't do that alone.

Also, the existence of a patent does not prevent or even impede the medical research or public health efforts being undertaken for MERS-CoV now. It also didn't hinder research on HCoV-NL63 or HMPV back when they were discovered. Have a look atPubMED (the Google for scientific research articles) and see how for yourself. There are hundreds of papers there that cover all aspects of each virus - virological, clinical, immunological impact and epidemiology. As a publisher of some of those papers I can assure you I was not asked to pay a cent to the "inventors" and the slowest part of the publication process was my own writing.

Comments to the World Health Assembly today have been interpreted to suggest that a patent on the MERS-CoV has delayed the development of diagnostic tests.

In fact, the necessary parts for leading edge diagnostic testing - sequences for polymerase chain reaction primers - were made available by the researchers (easily contactable thanks to a ProMED posting) as soon as they were developed. They were next made public to the entire scientific community through very rapid publications in leading journals. There are more than 20 papers on the MERS-CoV, or HCoV-EMC as it was known, listed on PubMED already. All a professional, PCR-enabled, public health or research diagnostic laboratory has to do is eMail the discoverers or read the manuscripts and order the reagents.

A true absence of information is unquestionably an impediment to infectious disease research. We saw some great examples of unfettered information from China during the H7N9 outbreak this year. When key information is freely available, as it has been from Prof Zaki and the Dutch researchers at Erasmus for the MERS-CoV, we can rest assured that diagnostic developments are unhindered. Diagnostics are most useful though when they are used to report when and how cases of infection by a new virus occur and spread. Could that area be the next target for more public criticism?

Flu season isn't the only season.

Its worth noting that when we talk about flu season we are talking about that time of year when flu cases peak. Its not flu season in the US now but there are still cases of influenzavirus spreading among humans. Its just not at epidemic levels (case numbers significantly above the norm).We are entering normal flu season in other parts of the world though, like down here in Aus, although cases are currently sparse. Cases of seasonal flu in one country can be easily spread to other countries by global travel. This is not just the case for influenza viruses of course. Any human respiratory virus ticks over at baseline levels outside of its main "season". Most of the time these infection come and go quickly and with relatively little illness.
Remember, viruses don't know the temperature outside, or the cloudiness - it's the hosts of infection that play the biggest role in virus activity.

Just normal viruses folks.

It seems that the cluster is a collection of normal respiratory virus infections. Its worth remembering that it is very hard to distinguish between the 200+ different respiratory viruses using signs and symptoms alone. What is usually a common cold virus has been found to trigger asthma attacks and been associated with middle ear infections, pneumonia, bronchitis, influenza-like illness...its a game of probabilities.

Certain viruses are usually cause certain disease. Usually is not always.
In the current climate of MERS-CoV and H7N9 it's understandable that an uptick in acute respiratory illness cases causes alarm but the odds are in favour of one the usual culprits today.

This event is also a reminder of the great job done by expert public disease diagnostic entities like the CDC during times of disease outbreak. Imagine the number of samples that get sent to the CDC for special investigations then scale that up logarithmically during outbreaks. Realistically, even during a pandemic, to find an answer to the type of infectious agent a patient may have requires many separate tests to be conducted on each sample. Time is needed to receive, log and store each patient specimen, to set up, add to and run the diagnostic methods, to carefully interpret the results, sometimes to repeat or add novel testing methods and then to report the results to an increasingly data-hungry public. There's a lot of specialist work in there - even with high throughput system in place these things take some time. We should remember that when reading headlines like "CDC still 'investigating' mystery illness". The implication could be that there is thumb twiddling going because a press releases doesn't appear as quickly as a pirated TV episode on a torrent site. Be assured that there are many steps in a process that seeks to get it right first time.

On a side note, this makes a great case for enhancing diagnostic testing capacity to detect seasonal and endemic respiratory viruses at the local hospital laboratory level. Its surprising how few labs regularly test for the 150+ known rhinoviruses or the 4 non-SARS/MERS coronaviruses for example - together called common cold viruses.

"Mystery" respiratory illness in Alabama, US.

The past couple of days has seen many reports on a growing number of cases of cluster of acute respiratory illness. The Alabama Dept of Public Health (ADPH) issued an alert yesterday requesting that care providers to be on the lookout for unexplained case of pneumonia.

Cases of interest present with fever, cough, shortness of breath and "something" on their chest x-rays. Upper airway swabs or aspirates have been requested from such cases, regardless of "quick flu" test results. To date, samples have been collected and sent to local labs and to the US CDC.

A total of 10 cases - including 2 deaths (30-40y of age ) - are yet to be linked to a suspected pathogen and are not epidemiologically linked to one another.
Two cases positive for influenza (H1N1 and a seasonal H3) have already been reported (rapid antigen point of care testing?) although the flu season is currently winding down in the US. Two patients have already been discharged.

The cluster of respiratory illness can be traced back to around April 19th. Preliminary testing results should be arriving from the CDC soon.

FluTrackers are keeping a close eye on every report here.

Making antibodies cross-react with H7N9.

Prof Peter Palese's group has been busy publishing several papers in the Journal of Virology. One report describes the creation of cross-reactive antibodies to H7N9 by making Newcastle disease virus (NDV; a very contagious bird virus that has already been established as a poultry vaccine backbone) produce the H7 haemagglutinin from North American birds (H7N1-3).
They did this by inserting a representative H7 protein coding sequence in between normal NDV genes. The serum collected from mice immunized with this recombinant virus could block a range of H7-containing influenza A viruses. A new vaccine candidate in the making.

Editor's Note #6.

I've finally started to rebuild the rhinovirus (HRV) page. For someone whose main interest is these little dudes...well, it was in a pretty woeful state. How embarrassment. Expect to see it take shape over the coming weeks.

H7N9 antibody in Vietnam.

A study by MF Boni and colleagues describe the presence of either specific, or cross-reactive antibodies (which can arise after infection by a different influenza virus, but react with the H7N9 test) to the avian influenza A(H7N9) virus. These antibodies were detected in the sera of a cross-section of people from south Vietnam and were found at higher titres (levels) than antibodies to H5 but below those to H9 viruses. Human seasonal influenzavirus antibody levels were much higher than avian levels.
The protein array method used may not be comparable to haemagglutination inhibition (HI) or neutralization assay.
Results revealed a general increase in the amount of anti-haemagglutinin (HA) IgG antibody with age. This is fairly normal as our exposures to virus accumulate an immune "memory" over time.

There was no significant difference whether the samples came from rural or urban locales or from areas known to often keep chooks in the backyard, versus areas that do not.

The H7N7 and H7N9 avian influenza viruses differ by only ten amino acids in HA so it is likely IgG to H7N7 will cross-react with the H7N9.

H7N9 comments from ASM 2013.

Prof Albert (Ab) Osterhaus noted during a panel at the American Society of Microbiology 2013 meeting in Denver, that an H7N9 virus capable of spreading efficiently from human-to-human might result in an enormous outbreak.
Prof Osterhaus pointed out that although H5N1 has been around for over a decade (and our research still has not answered all the questions we've raised) it still has not developed the ability to spread efficiently from human to human. He also feels that the "spillover" from birds (likely to be poultry) to humans is via the live bird markets (LBMs) in China-in some way. We must also be mindful of influenza being a seasonal infection so we may see a lull as we enter the warmer months but that it may return as the weather changes.
Prof Osterhaus also reminds us that "low-path" (low pathogenic avian influenza) virus are not necessarily "no-path" and that we shouldn't get too hung up on what may varies among, perhaps within, bird species as noted during lab studies. He also notes that the EMC team has developed a ferret model that provides human-relevant data on influenza infection and he stresses, continually, the importance of good epidemiology underpinned by ongoing surveillance systems.

Prof Robert Webster notes that LBMs may start to be reopened soon. He expressed his concern that H7N9 might re-emerge because of market reactivation. He also notes that poultry vaccines are "second-class" (Prof Osterhaus disagrees, says there arequality animal vaccines; H5N1 vaccines do not provide sterilising immunity - the chickens look good, but they keep shedding viruses - which is a hindrance to further vaccination of apparently healthy animals.

Dr Carole Heilman addresses the possibility of a universal vaccine noting that vaccines very conserved regions show promise in animals models. Current vaccine target the response to hemagglutinin - but what markers will be needed for vaccines focussing on eliciting other responses.

Prof Webster raises the issues of possibly "the most important avian influenza virus" H9N2, a virus spread ubiquitously across Eurasia, evolving in Bangladesh. H9N2 is stealthy in causing no apparent disease but is the backbone of H7N9. It may be the donor virus for many future reassortants.
Prof Osterhaus noted that much of what we have predicted about influenza virus over the years, hasn't happened-so lets keep predicting! However, H5N1 mutations, which are easy for the virus to accumulate, that could create an easily transmissible pandemic virus already exist in nature, some found in H7 and H9 viruses. Inexplicably, these mutations have not come together in humans yet. The potential exists however and complacency must be avoided.

In answer to a question expressing the public's concerns over escape or weaponization of lab-created "frankenflu" (my addition) viruses, Prof Osterhaus notes the high level of scrutiny and containment that these sorts of experiments are conducted under. He also notes that the biggest bioterrorist is nature.
In my opinion, the mutant flu virus research allows us to understand whether these mutations are possible and viable. The new viruses harbouring mutations of interest are "fit", they are able to replicate and transmit efficiently - some mutations make the virus less fit and so are unlikely to survive in nature. Understanding what is likely and what is not, helps researchers and public health officials develop policy, procedures and materials to be on guard for the greatest risks. Knowledge also helps us focus our research towards countering what could happen rather than stumbling around wasting time, effort and money on avenues that will not bear fruit in terms of increased public health and safety in an area that has a ticking clock a

Imported MERS death and 2 possible family cases in Tunisia.

It seems that up to 3 news cases of the MERS-CoV have

appeared in Tunisia (see updated map).ProMED (Archive# 20130520.1725864) crofsblog(multiple stories) and FluTrackers have more details and specifics.

According to a translated report, a 66M Tunisian citizen died after returning from the Saudi Arabia and Qatar, some of the "gulf states" (includes Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates). His two sons also have influenza-like illnesses, and they are positive for the MERS-CoV (Health Ministry via Kuwait News Agency report).

Its hard to tell but the (?)sons seem to be suffering a milder form of disease than perhaps we are used to hearing about. Which if so, once again raises the issues of how many mild cases are circulating that we are not hearing about, detecting or containing? Also I wonder how "close" these close contacts were in order to acquire infection and are any, more distant, contacts under observation-was 66M coughing and sneezing over his travel mates on the trip back from Tunisia?

Weekly H7N9 update from China: May 13-20.

No new H7N9 case reported in China!

1 new death of an existing case and 15 more discharges. 130 cases (132 if including the Taiwan import and asymptomatic case), 36 deaths and 72 recovered and discharged patients. No details on the death or discharges unfortunately.

All Australian bat species, including 1 of the 50 species of microbats (order Chiroptera [bats], suborder Microchiroptera) common in Australia, are considered susceptible to ABLV.

Chief Biosecurity Queensland officer Dr Thompson noted that a dead bat had been found on the property housing the Australian Bat Lyssavirus (ABLV) infected horse, but were not closely associated with any colonies.

All 6 human contacts of the horse have been given preventative treatment including rabies vaccine and rabies immunoglobulin, both of which cross-protect against serious disease caused by ABLV.

The main advice for humans to mitigate risk of infection is to avoid handling bats and flying foxes without appropriate vaccination. Even then, it would be best to report ill or strangely behaving (ill) bats to the authorities. Bats have been the source of a number of virus discoveries (not preventable by specific vaccines) in recent years including influenza virus (H17N10)and coronaviruses (numerous bat-CoVs and possible the MERS-CoV).

Is this what you think of when you think severe disease?

One of the treasures I've found while tinkering around the edges of H7N9 blogging for just a few weeks - Crawford Kilian's crofsblogs - the flu one in particular. 

I highly recommend this article from 19.05 highlighting the issue of taking MERS the virus and MERS the disease, seriously.

New MERS-CoV Page takes shape.

VDU is a "work-in-progress" kinda site. The latest work is to develop a new coronavirus page dedicated to the exploits of the latest of the betacoronavirus to infect humans. 

It has a way to go and will probably never have the colourful charts of the H7N9 page - data from the Arabian Peninsula has been nothing like the quality of those from China - but I'll bring it up to speed as I read through the literature, and then leave it as a resource for those wanting a grounding in what used to be (sniff) HCoV-EMC.

Sunny summer or birds on the wing?

I'm no ornithologist. Week 7 had much to say about the approaching summer scaring away the H7N9 virus and the closure of live bird markets having stunted or stopped entirely the outbreak. 

I'm still not convinced - as I said yesterday. 

A continuation of that line of thinking, posed as question for today then; could the spread of H7N9 have peaked and fallen in relation to the travels of wild birds, not poultry? The paltry number of positive poultry cases could have acquired their virus from wild birds also. 

Also, how many of the males infected with H7N9 kept small birds as pets? Did any of them get those birds recently? Passerine birds, like the brambling, cover some distances when migrating with the seasons. The brambling also turned up amongst as co-contributor (of an H9N2) to H7N9's genetic makeup.

Denominator example from WHO.

  Thanks to Mike Coston for the heads up on the WHO report resulting form the Influenza-A-team's Joint Mission to parts of China (18/24 April, 2013). They have a nice graphic on pg17 outlining the denominator issue. I've adapted for the H7N9 page.

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?

First ever horse infection with Australian bat lyssavirus (ABLV).

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

Haemagglutinin cleavage site graphic.

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.

Media MER muttering more than murmurs.

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.

41 HCoV-EMC Cases.

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.

Editor's Note #5.

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.

Stuff from the literature: Dabbling ducks respond to flu viruses.

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.

Hunan's first H7N9 case dies.

The tally rises to 36

MERS - clear as mud.

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.]

H7N9: the stealth bomber virus.

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.

1 new H7N9 case and 4 deaths.

This weeks case report (May 6 to May 13) describes the discharge of 15 new existing H7N9 cases, four deaths and a new case in Jiangxi. 

No further details to be had in the Ministry of Health release.

Welcome to Week 7 of the H7N9 outbreak.

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.

Matrix-targeted real-time PCR for H7N9.

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.

Off the air.

VDU has had some FTP issues with its server so no updates across the weekend. 

The University of Queensland quickly fixed the problem today.

Speculation Into Darkness.

As part of my crippled USS Vengeance-like crash course into the workings of influenza viruses over the past nearly 6 weeks, I've been doing some reading. 

A Science Policy Forum article I'm skimming through tonight, from Lipsitch and colleagues in 2012, makes a nice comment: 

We contend that predictions about how particular influenza strains will behave in humans or, even more important, how they will evolve, remain highly speculative. 

While this was written with H5N1 as the subject, it is clearly applicable to H7N9. It nicely sums up my understanding on this late Friday evening as well! And who needs a colon anyway?

H7N9 more transmissible than H5N1.

A comment in BMJ by Jane Parry stresses the use of closing live bird markets (LBMs)to halt human H7N9 cases and adds that this virus is more transmissible to/between humans than is H5N1 (45 human cases confirmed in China since 2001 vs H7N9's 132 but in only 5 weeks). 

I wonder how related this is to H7N9 being a low pathogenic avian influenza (LPAI) in birds compared to H5N1's highly pathogenic course in birds. H7N9 can, in theory, stealthily sweep through flocks without setting off veterinary alarm bells (human cases acting as the "sleeping" canary in the mine) whereas H5N1 triggers alarm and can be better controlled by early culling. 

So far 47,8000 samples from 1,000 farms and poultry markets have been been tested and only 39 have been H7N9 positive.

Fujian market H7N9 positive.

Sampling of the environment in a Fujian market yielded another positive. 

There are now 52 such samples positive according to the Ministry of Agriculture

Market networks.

A study by Fournié in PNAS and colleagues looks at risk and H5N1 and live bird markets (LBMs) in North Vietnam. Such sites implicated in H7N9's diverse and rapid spread in South East China, notes the interconnectivity between markets using social network analysis. Some act as hubs, spreading poultry to others. Infection in a hub will more effectively spread virus to outlying nodes. 

A similar, older study of Southern China LBMs provides insight into the number of sites affected by hubs and the vast distances travelled by poultry (with the help of humans and vehicles) in this area. It unfortunately doesn't cover the South East, the H7N9 hot zone, but I presume the pattern can be extrapolated. The 2011 study, by Martin and colleagues, focuses on markets in the Yunnan, Guangxi and Hunan provinces. It shows travel on one of many routes extending 2,500km (Yunnan to Shandong) and the importance of risk reduction measures (for H5N1) including daily poultry cage cleaning and disinfection and manure disposal/processing.

Haemodialysis to blame in MERS-CoV spread?

A translated article suggests that hospital infection control broke down and may be a factor in transmission.

Le MERS-CoV arrives in France.

A French citizen has been isolated in an intensive care unit somewhere in Paris after returning to France from the United Arab Emirates. 

The health website of the Ministry of Social Affairs and Health (Le site santé di Ministère des Affaires sociales et de la Santé) cites the National Reference Center at the Institute Pasteur as having confirmed the MERS-CoV (HCoV-EMC) case. 

This is not the Kingdom of Saudi Arabia (KSA) for the geographically challenged among us (I've added a map to the MERS-CoV page), so the virus is active in at least two sites unless this case visited KSA as well.

Losing control of the numbers?

That's how it was described to me by my esteemed colleague, the Editor in Chief of FluTrackers. 

For the past 5 week we've had fairly detailed data coming out of China about avian influenza A(H7N9) cases; dates, places, names, deaths, discharges., All these placed into the public domain and not just reported to Health officials through less public channels. 

Sure, I've griped about a missing number here and there in the past, but its not like I have a right to this information. Are these the data I'd like to see? No, I'd like to have seen prospective real-time RT-PCR-based (couple of assays targeting different regions) screening hospital outpatients, the community and including asymptomatic people, of all ages. I'd like to see serology on the vendors and those who frequently visit markets versus those who do not. And I'd like it all done yesterday. But that's flippant, and easy to say from my desk in my environment of instant gratification, some 7,330km away. Are these data from every single H7N9 case? Probably not, for a number of reasons. So, for some pure speculation. 

It just doesn't feel right. 130 cases spread over such a wide area, steep onset curves that suddenly halt, patents like Lee from Taiwan and others who claim no bird contact, so few severe cases among market vendors, evidence for asymptomatic and suspected clusters. 130 cases seems too low. More unreported cases may exist simply because we don't have all the results yet. Those may be coming down the pipeline. The time and effort to conduct screening and sequencing, collate data, cross-check and report results for humans and animals on the scale that is necessary to answer the questions being posed, is vast. China needs to juggle many other social and political issues around the reporting of deaths, illnesses and human-to-human transmission of this new virus. It has its own way of doing that. Most states do.

Nonetheless, scientists, policy makers, healthcare officials and vaccine producers (traditional and cutting edge) already have the information they need to get started on preparing for any future H7N9 pandemic.

• Vaccine seed strains have been circulated worldwide
• WHO influenza collaboration centres have positive H7N9 RNA controls for their RT-PCRs
• More RT-PCRs have since been developed to overcome the (not unexpected) deficiencies in first-generation assays
• Serological reagents are in use in China and in preparation elsewhere
• Key global health bodies have updated their pandemic plans
• We have estimates of incubation periods, clinical signs and symptoms indicating that severe acute respiratory disease cases look like....severe acute respiratory disease cases would be expected to look
• We know transmission may be happening between humans but inefficiently
• We know closing down wholesale poultry markets seems to correlate with a decrease in severe H7N9 cases in humans
• We've dusted off (ineffective) heat sensing cameras and (pointlessly) ill-fitting face masks again
• We have a good idea of what the wild host is (a bird...like it is for all influenza A viruses) just not evidence for which one or where it all started
• We've officially named our viral nemesis.

So all in all, we're not too badly off.

However Week 6, so far, has provided confirmation that publicly available case details have almost dried up.
The data we've had have been interesting and have allowed me to plot the detailed charts and graphs you've been viewing on the H7N9 page. Half of those views are from repeat visits. 

Today, my last hope faded for an update on those details for the recent 6 H7N9 deaths and the missing details on about 15 discharged patients. The WHO update had no new information in it at all. Perhaps other lists will be updated soon?

Here's hoping for some new data in the future, especially if that data should signal to the rest of the world that H7N9 has changed genetically, or a return of exponential rises in new H7N9 illness onsets such as we saw in Shanghai and Zhejiang. 

I think we have what we need to know that an H7N9 pandemic could emerge, but that one hasn't emerged yet.

The crowded virus escapes from Hofuf?

While MERS-CoV (f. HCoV-EMC) cases have been detected in the UK (3-2 fatal), Jordan (2-both fatal), the United Arab Emirates (1, fatal) and Qatar (2) since April 2012, it has been the Kingdom of Saudi Arabia (22 cases-13 fatal) that is the current hot zone. 

These cases are from 5 different clusters according to the FluTrackers. 

The latest news paints a bleak picture. According to the Wall Street Journal, Al Moosa General Hospital is not the only hospital treating patients from the current outbreak. 

Given that human-to-human transmission has been noted for MERS-CoV, this may nor bode well for containment.

It's an nHCoV, its an EMC...no...its MERS?

It was an unusual move that apparently required "a great deal of effort to find a name that all parties involved could agree on". Avian Flu Diary reports on a ScienceInsider article noting that the Coronavirus Study Group will propose an entirely new name for the latest human coronavirus type that seems to cause respiratory disease in humans and belongs to a new coronavirus species. 

Usually the International Committee on Taxonomy of Viruses (ICTV) doesn't fiddle around with naming below the level of species and the new human coronavirus type seems to be part of a group of viruses (including bat coronaviruses) that together will likely form a novel species. Do the bat viruses also cause respiratory syndrome in humans...or other animals? There is likely to be some (more) confusion caused by this name change, and it is very possible that the press will not strictly adhere to the new name any more than the old one (an argument that supports either side of the debate).

So far the virus has been called novel coronavirus (NCOV-a name that never should have stuck-what do we call the next one....more novel CoV?) and in the scientific, peer-reviewed literature, HCoV-EMC after the laboratory that characterized the virus (Erasmus Medical Center). Still, its only about 8 months since we learned of the first case subsequently attributed to this virus in Sept 2012 (the patient presented in June 2012). How big could the body of literature be on EMC at this point? Apparently its 23 papers strong according to PubMED.

The new name for the disease and the virus group will change to MERS-CoV (Middle East respiratory syndrome). It will next go before the ICTV for ratification.

H7N9 evolution: new graphic.

Based on the Liu et al. Lancet paper, this new graphic shows a possible series of evolutionary steps leading to the human-infecting influenza A(H7N9) virus.

H7N9 reaches high viral loads.

Large amounts of viral RNA were detected in 2 sputa and 1 throat swab collected from the imported Taiwan cases according to a recent Lancet letter. 

While early throat swabs (days after fever onset)and a chest X-ray did not indicate H7N9 infection, later in the disease course (11-13-days after onset of his 3-day fever) signs and virus became more clearly detectable. 

This case may suggest shedding is possible well before incapacitation and not long after a clinically indistinguishable episode of fever begins.

H7N9 deaths jump - details dry up.

H7N9-associated deaths now listed at being at 31 (last count 25-26). 

Details for 6 cases are limited but appear to have come from Anhui (1), Zhejiang (1) and Jiangsu (4). A new 9M case, apparently mild (fever, fatigue, diarrhoea), also reported in Fujian province - he's already discharged - found positive "retrospectively". Two items of interest here: (1) The delay in detecting the virus may simply reflect the lengthy average laboratory turnaround time (9d); (2) it seems the swabs were from the upper airways (throat), a site that has proven problematic for accurate testing so far. 

If sustained human-to-human transmission was an efficient means of spread....

Total H7N9 cases listed as 131 (likely to exclude Taiwan case [imported from mainland] and asymptomatic child case) and discharged patients now number 42.

Speaking of things we know little about...HCoV

HCoV-EMC cases have risen by three to a total of 30 (FluTrackers are running a nice tally). 

The latest severe acute respiratory illness (SARI) cases occur in Al-Ahsa and comprise a cluster of 13 cases. This is becoming a rapidly developing situation given that 18 cases have died overall. 

The spectre of underlying disease lurks here as it does with H7N9 but the evidence for human-to-human transmission seems more clear than for the flu. 

No host and little patient detail are also features of this outbreak.

Prof Peiris posits poultry progressing problem.

Esteemed virologist Professor Malik Peiris believes the drop in H7N9 cases linked to the shutdown in wet markets, underscores the impact of the large, fast-moving and diverse poultry trade in the south east of China. 

Wet markets have closed in all affected areas and cases have subsequently dropped. Prof Peiris noted that a study of human blood samples is underway. 

This will shed light on the proportion of cases, if any, that did not have severe enough disease to put them on the hospital radar or to lift them above the "noise" of normal upper respiratory tract infections, other respiratory diseases or pollution-exacerbated lung problems. 

The new study will provide a key piece of the H7N9 puzzle.

H7N9 risk for Canada's animals is negligible to very low.

Canadian Food Inspection Agency is not overly concerned that Canadian animals are at risk of intermingling with contaminated bird species.

Anger over anti-vaccination comment.

The entirely confusingly named Australian Vaccination Network (next month they will face a court battle to retain their misleading name), actually a cabal of anti-vaccination advocates, has encouraged parents to avoid vaccinating their children and do not rely on your GP's opinion. You know, those experts in community ills who often have there own children and have trained and worked for over a decade to ensure the community is healthy.

Instead, consult books, especially those penned by fringe writers who may have not knowledge or expertise in the science and medicine of infectious disease whatsoever.
As Australian Medical Association president Dr Steve Hambleton suggested, you can obtain facts from the Immunise Australia website and there is an excellent publication, produced by the Australian Academy of Science, The Science of Immunisation: questions and answers. 

The documents on these sites are fully up front about their being some risks, its just that these risks are generally very minor things like redness, soreness and swelling - probably nothing like that bruise little Johnny is sporting from school today or that bite Jenny inflicted on herself when she bit her own cheek at dinner last night.

 In comparison to acquiring the unadulterated disease against which these vaccines protect, its nothing to be unusually worried about.

Timeline of H7N9 events.

A new chart on the H7N9 page that puts key events on a timeline.

H7N9 outbreak Week 6 begins.

We start week 6 of the H7N9 outbreak with confirmation...or new test results....that H7N9 (not some other H7) is indeed among the poultry in Guangdong province, which is adjacent to Hong Kong. 

One sample was positive from s wholesale market in the city of Dongguan, which had previously (see post on 28.04) been positive for an H7 virus that was not H7N9.

Previous testing of 542 poultry workers (method unknown) in Guangdong had not identified H7N9 infection. As ProMED noted, in "AVIAN INFLUENZA, HUMAN (71): CHINA H7N9 UPDATE", this makes animals sentinels, instead of humans, for H7N9's presence for the first time during this outbreak. 

Shows the benefits of screening for virus without relying on symptomatic presentations hmm?

H7N9 Weekly wrap-up. Bird flu, what bird flu?

We finished Week 5 with astonishingly few new notifications and a lot more difficulty finding key dates for hospitalization, death and discharge. For example, a 55-year old male named Jiao from Hunan province has been variously cited as being the 25th or 27th death associated with H7N9. No-one seems to have a name for the 26th death. Just 1 disease onset and 2 deaths deaths during that period (see the many charts on the H7N9 page) making it the least fatal week of the outbreak. A total of 26 cases have been discharged from hospital (see Case chart on H7N9page, with perhaps another 9 unnamed discharges from Zhejiang. No new cases reported from Shanghai, Beijing, Anhui, Jiangsu, Henan or Shandong. Lab confirmations for cases with dates of onset preceding Week 5 appeared for Jiangxi, Fujian, Hunan and Zhejiang. 

Considering how steep the rate of confirmations was for Zhejiang in particular, the drop off is quite remarkable. The wet market closures seem to be the most popular factor in the decline of new (severe) human cases but there is still no word on prospective PCR screening for H7N9 among non-severe cases or among those without chronic underlying conditions.

So, as far as we know, pneumonia remains the most frequent indicator of H7N9 infection and that seem to be among mostly males with a constellation of underlying disease and infection. 

Week 5 saw a flurry of peer-reviewed scientific papers emerge. Some better-defined the clinical cases, other reported risks based on what we know from past influenzaviruses and others described the avian and genetic pathways for the parent and grandparent H7 and N9-containing viruses that seem to lead to the creation of H7N9. Intriguingly, there are still very few reports of H7N9 in the ducks, chickens and wild birds proposed as the hosts from which humans catch the virus.

While markets have been found to contain H7N9-positive birds, there are remarkably few human cases among market vendors or those working with the feather plucking machines (another proposed transmission route proposed during Week 5). Could vendors have pre-existing immunity? 

So another curious week with plenty of questions raised, but cases and deaths declining.

HCoV-EMC linked with 10 cases in 3 days.

FluTrackers, often the case as I've learned during the past 5 weeks, is the first to have all the info on the total 27 cases of infection by the newest human coronavirus ...to date. 

Nice graphic too.

New vaccine viruses get closer.

The WHO has released a document about its potential candidate vaccine viruses which are expected to available shortly.

Editor's note #4

VDU's Editor asked to comment on recent WHO statement about H7N9 severity on BBC World News' Newsday show with Rico Hizon. 

Video currently viewable at the Australian Infectious Diseases Research Centre at The University of Queensland.

New summary of H7N9 events.

The US CDC publish a wrap-up in an early release issue of Morbidity and Mortality Weekly Report.

Study supports poor H7N9 transmission - from anything!

A new paper in by J. Han et al. Emerging Microbes and Infection concludes that neither 2 vendors in an H7N9-positive poultry market visited by the H7N9-positive patient (our Case#10, also studied in recent Lancet article) nor his close contacts, were WHO RT-rtPCR positive. 

So picking up H7N9 is certainly not a frequent thing. Also supported by the few cases that have been identified considering the population in these areas that move through and interact with birds and the markets. 

Also, once you have it, transmitting H7N9 it seems to be an infrequent event.

Swapping H1N1's PA and NS into H5N1 flu helps H5N1 spread.

A new study by Hualan Chen's group at Harbin Veterinary Research Institute published in Science reveals that avian influenza A(H5N1) can acquire mammalian transmissibility if it acquires the right segments of human influenza A(H1N1). This was not a mutation study, but a whole gene segment-swapping study (creatingreassortants). 

This work was conducted in mice (for lethality studies) and guinea pigs (for transmission) and yielded different results compared to similar studies using ferret models, which did spread via aerosols or droplets.

Some have expressed their dismay at the study itself. It seemed to fly in the face of the many concerned scientists who wrote at length after similar studies, classified as 'gain of function' virus research, were described using mutations in flu genes, instead of entire gene segments. "Play" was pressed on the voluntary pause in highly pathogenic avian influenzavirus H5N1 research in Feb 2013 after a list of uber-expert flu researchers declared that sufficient time had passed, explanations, debates, reviews and revisions had occurred. 

Those scientists suitably supported and qualified to do so should get back to the bench in order to better prepare humanity for pandemic influenzas of the future. Timely. There were 3 Chinese affiliations as signatories on this article including Harbin Veterinary Research Institute's Prof Hualan Chen.

Whatever you think of this study, the outcome is a very sobering reminder of what chance could be capable of in those locations where animal and human flu viruses co-circulate. 

Fit and better-transmitting viruses can result.