Deadly H5N1 birdflu needs just five mutations to spread easily in people

Reference: Phys.org. 15 Apr 2014. Dutch researchers have found that the virus needs only five favorable gene mutations to become transmissible through coughing or sneezing, like regular flu viruses.

World health officials have long feared that the H5N1 virus will someday evolve a knack for airborne transmission, setting off a devastating pandemic. While the new study suggests the mutations needed are relatively few, it remains unclear whether they’re likely to happen outside the laboratory.

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H7N9: Historical prevalence and distribution of H7N9 among wild birds

Source: Posted by Ian M Mackay on Virology Down under. CDC Emerging Infectious Diseases published a paper (Volume 19, Number 12—December 2013) on the Historical Prevalence and Distribution of Avian Influenza Virus A(H7N9) among Wild Birds. A very interesting document, it provides a better understanding on transmission of H7N9 under wild birds.

In this paper, the authors reviewed 48 published studies that listed findings of influenza A virus haemagglutin type H7, or neuramonase N9 viruses as well as H9N2. The prevalence was calculated as the number of positive samples divided by the by number tested.

H7N9 has been rarely reported from Delaware (USA), Alberta (Canada), Guatemala, Spain, Egypt, Mongolia and Taiwan but has not been reported from Russia, Japan, South Korea or China from birds sampled between 1976-2012.

The outcome? If you were planning wild bird surveillance to track H7N9 spread in these non-poultry animals, you’ll need to sample >30,000 wild birds to find 1 positive for H7N9 (its Asian prevalence was 0.00931%).

That’s a rare bird.
This is just a rough gauge of course because it is entirely dependent on when, where and how thoroughly bird populations were sampled, how they were sampled, what they were tested with and how the sequencing methods performed. It also focuses on HA and NA genes, at the expense of other internal influenza gene segments which also have an important role in the assemblage of new viruses.

Related links to this topic published by FAO-USGS on Avian Influenza Projects related to migrating birds:

Avian Influenza transmission risk & the Migratory Ecology of African wild ducks
Avian Influenza transmission risk & wild birds in Nigeria
Bangladesh: A source of Highly Pathogenic H5N1 infection in wild birds?
Ecology and Conservation of Wild Birds in the Poyang Lake Region: a Satellite Telemetry Pilot Project
Investigating the role of swans and geese from Eastern Mongolia in the potential spread of avian influenza virus.
Migratory birds and transmission of Highly Pathogenic H5N1 in Turkey
Movements of migratory waterfowl in the Middle East: Identifying at-risk areas for spread of avian influenza into Egypt
Movements of Wild Birds and Emerging Disease Risk from Hong Kong
Movements of Wild Birds and Emerging Disease Risk from India
Wild Bird Migratory Ecology, Emerging Disease Risk and Physiology in Western Mongolia
Wild Birds and Emerging Diseases: Avian Influenza Transmission Risk and Movements of Wild Birds from Kazakhstan
Wild Birds and Emerging Diseases: Modeling Avian Influenza Transmission Risk Between Domestic and Wild Birds in China

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H7N9 in China: deaths jump significantly

Source: Posted on VDU’s blog by Ian M Mackay, Virology Down Under, 21 February 2014. Twitter was buzzing this morning with news that several sources had announced a new total number of deaths in human cases of H7N9 infection.

It was not a total surprise that there were more deaths than we had heard about, and that is for several reasons:

In Wave 1, Spring 2013 in South east China, there had been a greater proportion of deaths than we have seen in Wave 2. That’s seemed unusual.

After Wave 1, the proportion of fatal cases (PFC; see background here) sat up as high as 33%. Wave 2′s high case numbers but few reported deaths had lowered that to 18% at one point. If the virus hadn’t changed and human-to-human transmission had not changed then that was incongruous

The media were reporting higher numbers than we had data for in early Feb and in late Jan, Xinua reported 26 deaths in Zhejiang alone for 2014 – this far outstripped any publicly data available

So now we see that the tally is 112 fatal H7N9 cases among people infected with a laboratory confirmed H7N9 virus, since the outbreak began in 2013; that tally includes both waves of human cases. That makes the PFC among the 361 confirmed human cases at 31%. So this one new piece of news has bumped up the PFC by 10%. From 1:5 (22% last week) to nearly 1:3 cases dying after acquiring infection. Thankfully, H7N9 is not spreading efficiently among humans (or chickens according to reports). But these are numbers to care about. For comparison, my Excel sheet has 64 cases with data that I can cross-check (I believe that agrees with the FluTracker’s count also).

The last media update I looked at had a tally of 77 fatal outcomes.

So we have between 35-48 people have died without any ability for anyone outside China to link them to:

their age
when they became ill
where they were
how they may have acquired their infection
their sex
time to hospitalization and diagnosis
length of stay in hospital
what contacts they had and how they have fared.

I think that this is a ball that has been not just been dropped, but buried in a hole and covered over with feathers. I’m disappointed by such a gaping data loss. And don’t get me started about the absence of H7N9 sequences from 2014 cases!

Sources…

1) SCMP with higher death tallies than public data indicated

2) Xinhua lists 26 deaths in Zhejiang alone for 2014

3) VDU blog on missing deaths

4) Mike Coston’s Avian Flu Diary take one the new data, with other sources

5) FluTracker’s thread with links to eth WHO report

6) China’s Ministry of Agriculture report of enlarged H7N9 death tally

7) The WHO report under the “vaccines” section

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Is the Avian Influenza on the verge in Asia?

More human cases of avian influenza A H7N9 virus infection have been reported in China in the past year than with H5N1 viruses since their emergence in 1997. Is the Avian Influenza on the verge in Asia?

Both reopening of live poultry markets and seasonality might have contributed to an apparent re-emergence of H7N9 human infections in the past month. Whether cases of avian influenza A H10N8 virus infection are going to increase is unknown, because how widely these viruses are circulating in poultry is unknown.

More surveillance will be needed to establish the origin of H10N8 and to monitor potential future transmission events. Additionally, other new avian influenza virus subtypes, reassorting with H9N2 viruses, might emerge in the near future and cause human infections.

In December, 2013, Chinese health officials confirmed the first human case of avian influenza A H10N8 virus infection. In The Lancet, HaiYing Chen and colleagues report the clinical data for this case,3 which coincided with a second wave of avian influenza A H7N9 virus infections in eastern China. A woman aged 73 years was admitted to hospital and shown to have avian influenza A H10N8 virus infection, having become ill 4 days after visiting a live poultry market in Jiangxi province, China. The virus— designated as A/Jiangxi Donghu/346/2013(H10N8), henceforth JX346—was identified by sequencing of tracheal aspirate samples obtained 1 week after illness onset.

Preliminary phylogenetic analysis of the retrieved sequences suggests that JX346 originated through reassortment of H9N2 strains circulating in poultry and recorded in environmental samples from Jiangxi, with one or two viruses contributing haemagglutinin and neuraminidase genes. The data suggest that JX346 arose by reassortment events in domestic birds. JX346 has avian-like receptor specificity, which might contribute to the fatal outcome of infection. It was previously postulated that infection of lower lung sections expressing avian-like sialic acid receptors with avian influenza A H5N1 virus infection might determine the severity of infection outcomes.

So far, only two H10N8 viruses have been reported in China: one environmental isolate from a water sample in Hunan province, China, in 2007, and one from a live poultry market in southern China in 2012. However, phylogenetic analysis shows that JX346 is different from these previously identified viruses. Increased sampling efforts might identify the ancestors of JX346. Sequence analysis of the JX346 haemagglutinin gene shows no indications for a multi-basic cleavage site, suggesting low pathogenicity in poultry. As for the newly emerged avian influenza A H7N9 virus, this low pathogenicity will make surveillance efforts substantially more difficult.

JX346 is the third virus strain generated by re- assortment in avian species that are transmitted to people, and all internal gene segments (PB2, PB1, PA, NP,M,andNS) are derived from H9N2 viruses.The 1997 avian influenza A H5N1 viruses and the H7N9 isolates from China both carried all internal genes from H9N2. This gene cassette might thus be a genetic platform for new strains with zoonotic potential.
As reported by Chen and colleagues, the woman infected with avian influenza A H10N8 virus had several underlying medical conditions (hypertension, coronary heart disease, and myasthenia gravis) and had undergone a thymectomy in December, 2012, which together probably resulted in substantial immune deficiency.

So far, only one additional human case of avian influenza A H10N8 virus infection has been reported: on Jan 26, 2014, health authorities announced infection in a 55-year-old woman in Nanchang, Jiangxi province. This patient developed flu-like symptoms after visiting an agricultural market, and was admitted to hospital 1 week after onset of illness. More surveillance will be needed to establish the origin of H10N8 and monitor potential future transmission events.

Does H10N8 pose a pandemic threat?
The introduction of a new influenza A subtype into people is always a public health concern. However, pandemic viruses are characterised by high transmission. Sustained person- to-person transmission has not been reported with influenza A virus subtypes other than H1, H2, and H3 viruses, and so far H10 viruses are no exception. JX346 did not successfully spread to close contacts, and mild cases of H10N7 virus infection in Australia and Egypt did not transfer to exposed relatives.1 Experiments done to improve understanding of what is necessary for sustained transmission of avian H5N1 influenza A viruses in ferrets in laboratory settings showed several mutations throughout the viral genome (mainly in haemagglutinin and the polymerase complex) that are needed for this adaptation. Of those, JX346 shows PB1 polymorphisms at positions 99 and 368, which are associated with enhanced replication and transmissibility in ferrets, and the well characterised mammalian adaptation PB2 627KLys. However, despite more than 15 years of H5N1 transmission events from birds to people, none of these mutations resulted in a strain that could be transmitted between people.

How virulent is the H10N8 virus?
Although H10N8 is predicted to have low pathogenicity in poultry and other avian species, it is too early to say anything conclusive about its virulence in people because of the small number of cases. Even for avian influenza A H5N1 and H7N9 viruses, the real frequency of mild and asymptomatic infections is unknown, despite the many deaths associated with human infections, because diagnosis and detection is generally done only when patients are admitted to hospital, and therefore is biased towards severe cases.

While increased surveillance might also be responsible for the increase in number of human infections with avian viruses, most human infections are associated with avian viruses containing the H9N2 internal gene cassette, on the basis of available sequences. Studies are needed to understand how this internal cassette helps avian influenza viruses seemingly well adapted to poultry to also jump more frequently into people and cause disease.

read Lancet article, published online February 5, 2014:

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Some people less susceptible to H7N9 than others

An international team of researchers working at the University of Melbourne in Australia has found that genetic differences in people result in different degrees of ability to fight the H7N9 influenza virus. In their paper published in Proceedings of the National Academy of Sciences, the team reports that their study of immune response observed in blood samples indicates that some people may be far better equipped to fight off the new flu strain than others.

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Food Additive May Prevent H7N9 From Infecting Host Cells

As China continues to battle an outbreak of avian influenza A (H7N9), a team of researchers from the University of Illinois at Chicago College of Medicine are among those looking for ways to intervene and bring an end to a disease that has so far killed more than 20 percent of those it has infected. The university team, led by Michael Caffrey, associate professor of biochemistry and molecular genetics at IUC, has found a common food additive that can block a strain of the avian influenza virus from infecting healthy cells. They are now reporting this new discovery in a published paper in the online journal PLoS ONE.

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Lotta Berg 2009: WSPA conference Poultry welfare AI

In this paper various bird welfare aspects related to avian influenza and other contagious diseases are discussed. Disease outbreaks will, apart from the obvious direct effects on bird health, and thereby their wellbeing, also indirectly influence the welfare of the birds. For example, restrictions on outdoor access for free-range poultry may be imposed, and vaccination or testing schemes may lead to handling or sampling procedures that are stressful to the birds.

At the same time, the immediate risk of a disease outbreak may lead to improved biosecurity measures on farms, which may in turn decrease the risk of other diseases entering the premises, thus resulting in improved bird health and welfare.

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Gain of-function experiments on H7N9

Twenty-two researchers from labs across the world submitted a letter to Nature and Science yesterday detailing their proposed “gain-of-function” research on the avian influenza virus H7N9.

Their work would genetically engineer H7N9 to make it both more virulent and more readily transmissible person-to-person. The research sounds controversial, not the least because one of the scientists involved is Dr. Ron Fouchier, whose on gain-of-function work on H5N1 ingnited furious debate over what should research should and shouldn’t be published.

However, there is a very real possibility that H7N9 will naturally mutate to transmit effectively between people. We already know that the virus is just a single amino acid mutation away from becoming easily transmissible between people. Indeed, news of the first confirmed case of such transmission was published in the British Medical Journal this week.

With a 60% fatality rate and a completely naive global population, the results would be catastrophic. The proposed research would give us an idea of potential pandemic scenarios, giving us a head start on potential vaccine and antiviral development.

It may be controversial, but it’s absolutely necessary.

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Depopulation and disposal: training presentation

This training module is part of a series of outbreak response training for H5N1 in Egypt, 2008. It gives an overview of different methods and techniques and their applicibility under African circumstances. The ptaining was provided under the Better Training for Safer Food program of the European Uninion.

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Major Challenges in Providing an Effective and Timely Pandemic Vaccine for Influenza A(H7N9)

The arsenal of public health tools to reduce morbidity and mortality from an influenza pandemic is limited. Options include vaccines, antiviral drugs, and interventions such as respiratory protection and social distancing. In a statement The World Health Organization (WHO) described the importance of a vaccination strategy:

“Influenza vaccination is the most important intervention in reducing the impact of influenza, and a key component of the WHO response and preparedness efforts for influenza of pandemic potential, including avian influenza A(H5N1), A(H9N2) and A(H7N9).”

Data for seasonal influenza vaccines and the 2009 A(H1N1)pdm09 vaccines provide a basis for estimating potential effectiveness of A(H7N9) vaccines. Inactivated seasonal influenza vaccines have a pooled efficacy estimate of 59%, primarily for younger adults. A paucity of evidence exists for demonstrating protection in adults aged 65 years or older, particularly with influenza A vaccines.

Three primary scenarios exist for how this A(H7N9) virus outbreak will unfold:

1. The virus could disappear in the animal reservoir, ending new human cases
2. The virus could persist in the animal reservoir, resulting in sporadic human infections.
3. The virus could, through mutation or reassortment, become readily transmissible between humans, resulting in a global pandemic.

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