Showing posts with label Potential. Show all posts
Showing posts with label Potential. Show all posts

Thursday, March 12, 2015

H7N9: Primus Inter Pares?

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  Credit Eurosurveillance

 

# 9813

 

Although well known (and respected) by infectious disease geeks, yesterday’s publication in Nature: Dissemination, Divergence & Establishment of H7N9 In China has suddenly thrust this H7 avian flu virus into the limelight, casting it in the role of the potentially driving the next influenza pandemic.


It isn’t alone, of course.  There are other pandemic contenders out there, including the venerable H5N1 virus.

 

But H7N9’s rapid spread, and growing genetic diversity in China – combined with its ability to infect humans – has seemingly elevated it to the level of  Primus inter pares – or `first among equals’ – in the pandemic flu world. 

 

Overnight we’ve seen a plethora of headlines heralding the threat:

 

H7N9 bird flu has the makings of a pandemic virus, scientists warn

Scientists warn H7N9 bird flu may pose pandemic threat

Bird Flu Mutating in China, Threatens Pandemic

Report: H7N9 bird flu has makings of pandemic

 

While yesterday’s report in Nature provides more information, and includes a stern warning about its implications, this isn’t the first study to cast H7N9 in a possible pandemic role.  Very early on after it appeared in China in the spring of 2013 we began to hear warnings from scientists, and over the past couple of years, we’ve followed the virus’s evolution.

 

In June of 2014, in Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission, we saw evidence of the genetic diversity, and continual evolution, of the H7N9 virus in Mainland China.  Researchers found that at least 26 separate genotypes had emerged, mostly during the first wave, through a process they called `genetic tuning’.

 

Yesterday’s report expands that array of genotypes to 48, divided among three well defined clades, and even includes a previously unrecognized subtype – H7N6 - in chickens.  Previously, during the first wave in 2013, a new H7N7 virus was also recognized (see Nature: Genesis Of The H7N9 Virus).


The power, and the threat, of H7N9 isn’t simply that it could pick up the `right’ mutations and become fully transmissible in humans, thereby sparking a pandemic.   It’s that H7N9 is genetically malleable enough to serve as a stepping stone – or bridge – to a completely new subtype. 


As we’ve seen over the past couple of years with the sudden expansion of the HPAI H5 universe – which now encompasses H5N1, H5N2, H5N3, H5N5, H5N6, and H5N8 -  H7N9 seems poised to grow the H7 flu line as well.

 

Two years ago we really only had one avian flu virus we worried about; H5N1.  But in the spring of 2013 the novel flu field was joined by the unexpected arrival of highly pathogenic (in humans) H7N9 virus, which spread stealthily, and asymptomatically in chickens.  

 

And over the next 12 months, we saw a parade of new subtypes begin to emerge, including H6N1, H10N8, H5N2, H5N3, H5N6 and H5N8.

 

The process by which these new subtypes evolve is called reassortment, and that can happen anytime a single host is simultaneously infected with two different flu subtypes. 

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For avian viruses, birds are the obvious host of choice, while swine flu viruses reassort primarily in pigs.  But any susceptible host can produce a reassortant virus, including dogs, cats, horses, and humans.  

 

Fortunately, most reassortant viruses are evolutionary dead ends – unable compete against existing viruses.  But increasingly over the past few years, we are seeing `biologically fit’ reassortants emerge, capable of holding their own, and even thriving in the wild.

 

Last month, in HK’s Dr. Ko Wing-man On Flu Reassortment Concerns, we looked at the very real concerns expressed by Hong Kong’s Director of their Centre for Health Protection, that H7N9 could reassort with H3N2 during their particularly heavy flu season.

 

It is not an unreasonable concern.  While rarely detected, co-infections with two flu subtypes do occur, and probably more often than we suspect.  

 

Previously, in the Lancet: Coinfection With H7N9 & H3N2, we saw the first evidence of co-infection with the newly emerged H7N9 virus and a seasonal flu virus in a human. While last October, in EID Journal: Human Co-Infection with Avian and Seasonal Influenza Viruses, China, we looked at co-infections in 2 patients in Hangzhou, in January 2014.

 

In all of three of these cases, no reassortant virus was detected.

 

But In 2011,  an influenza co-infection in Canada led to the creation of a unique hybrid reassorted virus (see Webinar: pH1N1 – H3N2 A Novel Influenza Reassortment), although it was not passed on to anyone else.

 

In recent years we’ve seen a growing list of novel (avian, swine, canine, even seal) flu viruses emerge (H5N3, H5N2, H5N5, H5N6, H5N8, H7N9, H10N8, H10N7, H3N8, H6N1, H1N1v, H1N2v, H3N2v, etc. . .), and each carries some risk of reassortment. 

 

With other novels viruses, or with human viruses. Or conceivably both.

 

Over the past couple of years, the number of novel flu threats has grown dramatically, and that growth spurt shows no signs of abating.  With more and more influenza subtypes, clades - and genotypes within these clades - circulating,  Nature’s laboratory gets more `interchangeable parts’  to play with. 

 

While a pandemic may not be imminent, given the amount of `viral chatter’ we are hearing, the threat level is certainly elevated.  And by the time it is obvious that a pandemic threat has emerged, our `lead time’ to prepare may be down to weeks.

 

Two weeks ago, the World Health Organization released a statement called Warning signals from the volatile world of influenza viruses   where they cautioned:

Warning: be prepared for surprises

Though the world is better prepared for the next pandemic than ever before, it remains highly vulnerable, especially to a pandemic that causes severe disease. Nothing about influenza is predictable, including where the next pandemic might emerge and which virus might be responsible. The world was fortunate that the 2009 pandemic was relatively mild, but such good fortune is no precedent.

 

Whether the next big global health crisis stems from H7N9, H5N1, a new flu reassortant, MERS-CoV, or `Virus X’ – the one we don’t know about . . .  yet – our level of preparedness will, in large measure, determine its impact.

 

Now is the time for agencies, organizations, businesses, communities, and families to dust off their pandemic plans, review them, and make any needed refinements.  

 

You do have a pandemic plan, don’t you?

 

For some recent pandemic preparedness blogs, you may wish to revisit:

 

Do You Still Have A CPO?
Pandemic Planning For Business
NPM13: Pandemic Planning Assumptions
The Pandemic Preparedness Messaging Dilemma

Monday, July 22, 2013

H7N9: Disagreement Over Ferret Transmissibility Study

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Photo Credit Wikipedia

 

 

# 7505

 

 

A recent study by Chinese scientists from the Harbin Veterinary Research Institute and the Gansu Agricultural University, called H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet, suggests that the H7N9 virus may be better equipped to spread among humans than previously believed.

 

We looked at its findings last week In Science: H7N9 Transmissibility Study In Ferrets.

 

Researchers found the virus not only binds well to human (a2,6) receptor cells, it replicates efficiently in ferrets, and at least one isolate transmitted efficiently via respiratory droplets.

 

In an interview last week with CIDRAP NEWS, senior author Hualan Chen, PhD said, "The transmission of AH/1 to all three ferrets suggests that the H7N9 virus has great pandemic potential."

 

We’ve seen a number of other studies over the past few months expressing similar concerns over H7N9’s pandemic potential, including:

 

Chinese Science Bulletin: Early H7N9 Risk Analysis

Nature: H7N9 Pathogenesis and Transmissibility In Ferrets & Mice
Branswell: Studies Show Transmissibility Of H7N9 In Ferrets

 

Despite these worrisome studies, we’ve seen a huge drop off of reported H7N9 cases over the past couple of months. Closure of live markets and warm summer temperatures have been largely credited, but the near total absence of new cases remains a bit of a mystery.

 

Which brings us to comments yesterday by Zeng Guang - Chief Epidemiologist at China’s CDC – who doesn’t fully agree with the conclusions of Dr. Chen.

 

Findings on virus 'not strong enough' to affect strategy

Updated: 2013-07-22 08:17
By Shan Juan (China Daily)

A recent study that suggests the H7N9 avian influenza virus may be highly transmissible among humans is not strong enough to lead to any changes in the current H7N9 epidemic intervention strategy, said a senior Chinese scientist.

 

A study published on the website of the US journal Science on July 18 said the new strain of bird flu virus is highly transmissible among ferrets, a widely used animal model for studying how flu might spread in humans.

 

Consequently, it is possible the virus could efficiently spread among humans eventually, posing a pandemic risk, according to the study led by Chen Hualan, director of China's National Avian Influenza Reference Laboratory at Harbin Veterinary Research Institute.

 

Zeng Guang, chief epidemiologist at the Chinese Center for Disease Control and Prevention, disagrees with that conclusion.

 

"The findings are mainly based on animal tests in the lab that have not been witnessed or substantiated among the H7N9 human cases reported. So it shouldn't affect current intervention efforts or strategy at all," he said.

 

"So far, no substantial evidence of H7N9 spreading among humans has been detected," he said.

 

The study showed one virus isolated from humans was able to transmit efficiently among ferrets through respiratory droplets, raising the possibility of eventual airborne transmission among humans.

 

The study also warned that the nonpathogenic nature of the H7N9 virus in poultry enables it to "replicate silently" in avian species and be transmitted to humans, providing further opportunities for the virus to acquire more mutations and become more virulent and transmissible in the human population.

 

(Continue . . .)

 

 

While he may not be convinced that these lab findings currently translate into the field, Zeng did go on to say:

 

"We have to carefully watch the epidemic situation in the coming autumn, when the virus mobility tends to increase.”

 

A sign that no one is taking this summer’s welcomed lull in new cases as any kind of guarantee of what we’ll see this fall and winter.

Friday, May 10, 2013

MIT: The Risks Of An Emerging H3N2 Pandemic Virus

 

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Credit Wikipedia

 

# 7259

 

 

At the risk of piling on this morning, even as we track H7N9 and nCoV, it is worth recalling that last summer our attention was heavily focused on outbreaks of several variant swine flus, which infected hundreds of people who attended state and county fairs across the Midwest.

 

Asymptomatic Pigs: Revisited
MMWR: H3N2v Related Hospitalizations In Ohio – Summer 2012
The Return Of H1N1v

 

While we talk about the H3N2 virus as if it were a single entity – or at worst, a handful of strains - in truth there are more than a thousand variations of that virus, and most are currently only found in pigs and swine.

 

Descendents of the 1968 pandemic H3N2 virus continue to circulate outside of the human population, which has led researchers at MIT to consider its pandemic potential in a new study that appears today in Nature’s Scientific Reports.

 

Antigenically intact hemagglutinin in circulating avian and swine influenza viruses and potential for H3N2 pandemic

Kannan Tharakaraman, Rahul Raman, Nathan W. Stebbins, Karthik Viswanathan, Viswanathan  Sasisekharan & Ram Sasisekharan

Article number: 1822  doi:10.1038/srep01822
Received  21 December 2012 
Accepted 23 April 2013
Published 10 May 2013

The 2009 swine-origin H1N1 influenza, though antigenically novel to the population at the time, was antigenically similar to the 1918 H1N1 pandemic influenza, and consequently was considered to be “archived” in the swine species before reemerging in humans.

Given that the H3N2 is another subtype that currently circulates in the human population and is high on WHO pandemic preparedness list, we assessed the likelihood of reemergence of H3N2 from a non-human host.

(Continue . . . )

 

Follow the link to read the entire (and highly technical) study.

 

But briefly, what these researchers found was a wealth of H3N2 strains circulating in pigs and birds that are antigenically different enough from the strains that have circulated in humans to have pandemic potential.

 

For more on this, in a less technical vein, we go to this MIT press release.

 

Potential flu pandemic lurks

MIT study identifies influenza viruses circulating in pigs and birds that could pose a risk to humans.

Anne Trafton, MIT News Office

May 10, 2013

In the summer of 1968, a new strain of influenza appeared in Hong Kong. This strain, known as H3N2, spread around the globe and eventually killed an estimated 1 million people.

 

A new study from MIT reveals that there are many strains of H3N2 circulating in birds and pigs that are genetically similar to the 1968 strain and have the potential to generate a pandemic if they leap to humans. The researchers, led by Ram Sasisekharan, the Alfred H. Caspary Professor of Biological Engineering at MIT, also found that current flu vaccines might not offer protection against these strains.

 

“There are indeed examples of H3N2 that we need to be concerned about,” says Sasisekharan, who is also a member of MIT’s Koch Institute for Integrative Cancer Research. “From a pandemic-preparedness point of view, we should potentially start including some of these H3 strains as part of influenza vaccines.”

 

The study, which appears in the May 10 issue of the journal Scientific Reports, also offers the World Health Organization and public-health agencies’ insight into viral strains that should raise red flags if detected.

 

<SNIP>

Genetic similarities

 

In the new study, the researchers compared the 1968 H3N2 strain and about 1,100 H3 strains now circulating in pigs and birds, focusing on the gene that codes for the viral hemagglutinin (HA) protein.

 

<SNIP>

 

Seeking viruses with an antigenic index of at least 49 percent and glycan-attachment patterns identical to those of the 1968 virus, the research team identified 581 H3 viruses isolated since 2000 that could potentially cause a pandemic. Of these, 549 came from birds and 32 from pigs.

(Continue . . . )

 

 

 

 

Until a few years ago it was widely believed that a variant of a currently circulating flu strain – like H1N1 or H2N2 – would have a tough time sparking a pandemic as levels of community immunity would be too high. 

 

The events of 2009 have shown that to be a false assumption.

 

At the time we were intently focused on the H5N1 avian flu, only to have an upstart H1N1 virus unexpectedly jump from swine to humans in North America, and spark the first pandemic in more than 40 years. 

 

All of which should serve as a sober reminder that as we focus on the events in China and the Middle East, that nature can throw us a curveball from practically any direction.