CDC’s Key Facts On The New H3N2 Canine Flu

Credit CDC - Healthy Pets Healthy People

 

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Two weeks ago, in Midwest Canine Influenza Outbreak Due To `New’ Korean H3N2 Virus, we learned that an outbreak of canine influenza which began a month or so ago around Chicago was due to an Asian H3N2 canine flu subtype which emerged in 2007 (see Transmission of Avian Influenza Virus (H3N2) to Dogs). 

How this emerging influenza subtype managed to jump from Korea (or perhaps China) to the United States is unclear. But now that it is here, it appears to be spreading rapidly through an immunologically naive dog population. 

 

Unlike our domestic canine H3N8 - which jumped from horses to dogs in 2004, and has circulated in North America sporadically since then - this subtype has also been shown capable of infecting cats as well (see Korea: Interspecies Transmission of Canine H3N2). 

 

Adding yet another wrinkle, this H3N2 virus appears to be of avian origin. The HA and NA of the A/canine/Korea/01/2007 (H3N2) isolate was closely related to those identified from South Korean chickens and doves in 2003.

 

As with the existing equine and canine strains of H3N8, we’ve not seen any evidence of human infection with this canine H3N2 virus. But like all influenza viruses, canine H3N2 is a continually moving target.  It can not only evolve via antigenic drift, it can also pick up entire gene segments from other flu viruses via antigenic shift (aka reassortment).

And while rare, as any virologist will tell you – shift happens.

 

Last summer we saw evidence of just such an event, in a report appearing in the journal Epidemiology & Infection, that  found a new reassortment of the canine H3N2 virus – one that had picked up the M (matrix) gene from the 2009 H1N1 pandemic virus (see Canine H3N2 Reassortant With pH1N1 Matrix Gene) – in china.

 

When found in reassorted swine variant viruses, The CDC has speculated that `This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’ – CDC HAN 2012

 

But so far, we’ve seen no evidence that this canine H3N2 can infect humans.

 

This week the CDC published a new updated FAQ file on Canine influenza, specifically addressing this newly arrived subtype, including whether it has the potential to jump to humans.  I’ve excerpted the first two segments, so follow the link to read it in its entirety.

 

 

Key Facts about Canine Influenza (Dog Flu)

What is canine influenza (dog flu)?

Canine influenza (also known as dog flu) is a contagious respiratory disease in dogs caused by specific Type A influenza viruses known to infect dogs. These are called "canine influenza viruses." Dog flu is a disease of dogs. No human infections with canine influenza have ever been reported. There are two different influenza A dog flu viruses: one is an H3N8 virus and the other is an H3N2 virus.

Can canine influenza viruses infect humans?

To date, there is no evidence of transmission of canine influenza viruses from dogs to people and there has not been a single reported case of human infection with a canine influenza virus.

However, influenza viruses are constantly changing and it is possible for a virus to change so that it could infect humans and spread easily between humans. Human infections with new influenza viruses (against which the human population has little immunity) are concerning when they occur. Such viruses could present pandemic influenza threats. For this reason, CDC and its partners are monitoring the canine influenza H3N8 and H3N2 viruses (as well as other animal influenza viruses) closely. In general, canine influenza viruses are considered to pose a low threat to humans.

Where did canine influenza viruses come from and how long has it been around?

What are signs of canine influenza infection in dogs?

How serious is canine influenza infection in dogs?

How is canine influenza spread?

Is there a test for canine influenza?

Is there a vaccine for canine influenza?

My dog has a cough. What should I do?

Where can I find more information on canine influenza virus?

ECDC Rapid Risk Assessment On `Drifted’ H3N2 Viruses

Credit NIAID

 

 

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While we often talk about seasonal strains (H1N1, H3N2, Influenza B) as if they were individual entities – in truth within each subtype there are many clades and variants - and they are all evolving over time. Geographically, these viruses can vary widely, and so the dominate strains in Europe may differ from the dominant strains in North America or Asia.

 

Over time, new, more biologically `fit’ viruses replace older strains as community immunity drives them closer to obsolesce.

 

All which makes the flu world dynamic and ever-changing, and presents a genuine challenge for vaccine manufacturers to stay ahead of. NIAID has a terrific 3-minute video that shows how influenza viruses drift over time, and why the flu shot must be frequently updated, which you can view at this link.

Over the summer it was becoming apparent that a new, `drifted’ H3N2 virus was making inroads in Europe and around the globe (see ECDC: Influenza Characterization – Sept 2014) – one that differed antigenically from this year’s H3N2 vaccine strain. 

 

In September the WHO announced a strain change for next year’s Southern Hemisphere vaccine to meet this viral challenge, but this virus emerged far too late in the year to allow changes to this fall’s Northern Hemisphere vaccine.

 

In early November, in A `Drift’ In A Sea Of Influenza Viruses, I wrote about early concerns over this year’s vaccine, and in the first week of December the CDC issued a HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus along with a warning that  Early Data Suggests Potentially Severe Flu Season.

 

Today the ECDC has issued their own Risk Assessment on this `drifted’ flu strain.

 

Rapid risk assessment: circulation of drifted influenza A(H3N2) viruses in the EU/EEA, 22 December 2014

22 Dec 2014

Available as PDF in the following languages

EN

This document is free of charge.

Abstract

Surveillance data gathered since 1 October 2014 indicate that in the first ten weeks of the 2014–15 influenza season, viruses in EU/EEA countries have been predominantly A(H3N2) rather than A(H1N1)pdm09 and type B viruses. In previous seasons, influenza A(H3N2) viruses were associated with more severe disease than A(H1N1) and type B viruses; they were also associated with several outbreaks in long-term care facilities.

These observations indicate that the 2014-15 influenza season may be associated with a greater number of cases with more severe disease, given the higher proportion of A(H3N2) strains among isolates typed to date and the early evidence of drift that is likely to be associated with reduced vaccine effectiveness.

Influenza vaccine coverage among the elderly and the risk groups in most parts of Europe is low. However, the benefits of vaccination are considerable in protecting these population groups, even if vaccine effectiveness against one of the circulating viruses may turn out to be low.

 

 

  I’ve excerpted the following from the full report:

 

Main conclusions and recommendations

Surveillance data gathered since 1 October 2014 indicate that in the first ten weeks of the 2014–15 influenza
season, viruses in EU/EEA countries have been predominantly A(H3N2) rather than A(H1N1)pdm09 and type B  viruses. In previous seasons, influenza A(H3N2) viruses were associated with more severe disease than
A(H1N1) and type B viruses; they were also associated with several outbreaks in long-term care facilities.

The recently published US CDC health alert network notification on antigenically drifted influenza A(H3N2) viruses is the first signal from a northern hemisphere country that circulating viruses will include strains that are antigenically distinct from the A(H3N2) vaccine virus, A/Texas/50/2012, which was recommended by WHO for the northern hemisphere 2014–15 season at the February 2014 strain selection meeting.

Very few influenza virus characterisations have been conducted to date in EU/EEA countries, and the majority of them have been genetic rather than antigenic. The genetic information reported so far suggests the following:

• Influenza A(H3N2) viruses circulating in EU/EEA countries this season will be antigenically distinct from the  northern hemisphere A(H3N2) vaccine virus.
• Early indications are that circulating A(H1N1)pdm09 viruses are antigenically similar to the vaccine virus.
• Too few type B viruses have been characterised to date to comment on the likely effectiveness of the B/Massachusetts/2/2012 vaccine component.
  

These observations indicate that the 2014-15 influenza season may be associated with a greater number of cases with more severe disease, given the higher proportion of A(H3N2) strains among isolates typed to date and the early evidence of drift that is likely to be associated with reduced vaccine effectiveness.

Despite the expected low vaccine effectiveness (VE) of the A(H3N2) vaccine virus component in the vaccines administered for protection in the 2014–15 influenza season, the current tri- and quadrivalent vaccines are likely to provide protection against infection by other currently circulating influenza viruses. Even with low VE of the A(H3N2) vaccine virus components, the vaccine may ameliorate or shorten the duration of influenza disease in infected individuals and is likely to reduce the number of severe outcomes and mortality. Influenza  vaccination remains the most effective measure to prevent illness and possibly fatal outcomes.

The circulating viruses are susceptible to the antiviral drugs oseltamivir and zanamivir. Physicians should therefore always consider treatment or post-exposure prophylaxis with antivirals when treating influenza infected patients and exposed individuals in risk groups.

Influenza vaccine coverage among the elderly and the risk groups in most parts of Europe is low.

However, the benefits of  vaccination are considerable in protecting these population groups, even if vaccine effectiveness against one of the circulating viruses may turn out to be low.

CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus

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Late yesterday the CDC issued a HAN Advisory for clinicians on the possibility of seeing `drifted’ H3N2 virus infections during this year’s flu season, along with a reminder on the appropriate and timely use of antivirals. 

 

If this sounds familiar, we looked at this possibility at some length a little over a month ago in A `Drift’ In A Sea Of Influenza Viruses.

 

But briefly, over the summer – and since this year’s flu vaccine components were selected last February – a new, antigenically drifted H3N2 virus has begun to circulate more widely.

 

The rise of this new strain has already prompted  WHO to recommend a strain change for next year’s Southern Hemisphere vaccine formulation from the current A/Texas/50/2012 (H3N2)-like virus to a new A/Switzerland/9715293/2013 (H3N2)-like virus.

 

The most recent FluView report (week 47) shows that of the 85 H3N2 viruses tested since October 1st, 41 (48%) are a good match to the vaccine strain, while 52% were not.  This `mismatch’ is expected to reduce the vaccine’s effectiveness against this drifted strain, although some protection or a reduction in the severity of illness may still result.

 

With this year shaping up to be an H3N2-dominant year, and a possible vaccine `mismatch’ in the works, the CDC is reminding clinicians of value of prescribing neuraminidase inhibitor antiviral medications for severe influenza, or for patients with co-morbidities that raise their risk of seeing serious complications.

 

Despite the constant excoriation of Tamiflu ® and other NI antiviral medications in the press – based primarily on a series of Cochrane reports (see Revisiting Tamiflu Efficacy (Again)) – there are demonstrable benefits to using these medications, particularly when given early and for severe influenza (see The CDC Responds To The Cochrane Tamiflu Study).

Earlier this summer we saw a review in the journal Clinical Infectious Disease that suggested a serious Under Utilization Of Antivirals For At Risk Flu Patients, and a month ago we saw the UK’s PHE reiterate their Influenza Antiviral Recommendations.

 

Although you can never be sure what kind of flu season we will have until it is over, years in which H3N2 viruses have dominated tend to be rougher for the elderly, and the very young,  than years when H1N1 or influenza B dominate. 

 

Despite the expected reduced effectiveness of this year’s flu shot, there are still benefits to getting the vaccine if you haven’t done so already. 

• There are two other strains (H1N1 & Influenza B) covered by the shot,
• Half the H3N2 viruses tested so far are still a `match’  to the vaccine strain
• There may still be some degree of cross-protection afforded against this new strain.

I’ve only posted the summary, so follow the link below to read the full HAN advisory, and the recommendations of antiviral use.

 

CDC Health Advisory Regarding the Potential for Circulation of Drifted Influenza A (H3N2) Viruses

 

CDC HEALTH ADVISORY

Distributed via the CDC Health Alert Network
December 3, 2014, 16:00 ET (4:00PM ET)
CDCHAN-00374

CDC is reminding clinicians of the benefits of influenza antiviral medications and urging continued influenza vaccination of unvaccinated patients this influenza season.

Summary

Influenza activity is currently low in the United States as a whole, but is increasing in some parts of the country. This season, influenza A (H3N2) viruses have been reported most frequently and have been detected in almost all states.

During past seasons when influenza A (H3N2) viruses have predominated, higher overall and age-specific hospitalization rates and more mortality have been observed, especially among older people, very young children, and persons with certain chronic medical conditions compared with seasons during which influenza A (H1N1) or influenza B viruses have predominated.

Influenza viral characterization data indicates that 48% of the influenza A (H3N2) viruses collected and analyzed in the United States from October 1 through November 22, 2014 were antigenically "like" the 2014-2015 influenza A (H3N2) vaccine component, but that 52% were antigenically different (drifted) from the H3N2 vaccine virus. In past seasons during which predominant circulating influenza viruses have been antigenically drifted, decreased vaccine effectiveness has been observed. However, vaccination has been found to provide some protection against drifted viruses. Though reduced, this cross-protection might reduce the likelihood of severe outcomes such as hospitalization and death. In addition, vaccination will offer protection against circulating influenza strains that have not undergone significant antigenic drift from the vaccine viruses (such as influenza A (H1N1) and B viruses).

Because of the detection of these drifted influenza A (H3N2) viruses, this CDC Health Advisory is being issued to re-emphasize the importance of the use of neuraminidase inhibitor antiviral medications when indicated for treatment and prevention of influenza, as an adjunct to vaccination.

The two prescription antiviral medications recommended for treatment or prevention of influenza are oseltamivir (Tamiflu®) and zanamivir (Relenza®). Evidence from past influenza seasons and the 2009 H1N1 pandemic has shown that treatment with neuraminidase inhibitors has clinical and public health benefit in reducing severe outcomes of influenza and, when indicated, should be initiated as soon as possible after illness onset. Clinical trials and observational data show that early antiviral treatment can:

• shorten the duration of fever and illness symptoms;
• reduce the risk of complications from influenza (e.g., otitis media in young children and pneumonia requiring antibiotics in adults); and
• reduce the risk of death among hospitalized patients.

(Continue . . .)

 

MIT: The Risks Of An Emerging H3N2 Pandemic Virus

 

Credit Wikipedia

 

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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. 

CIDRAP: MRSA Pneumonia Suspected In Calvert County Flu Cluster

 

Clumps of methicillin-resistant Staphylococcus aureus – Credit CDC PHIL

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Although we haven’t seen any official updates since late yesterday afternoon, reports have been trickling in through various media outlets suggesting that the fatal flu cluster in Lusby, Md.  involved the seasonal H3N2 virus and an aggressive form of MRSA pneumonia.

 

Lisa Schnirring of CIDRAP News  brings us up to date this evening with this report.  Follow the link to read her report in its entirety.

 

 

MRSA pneumonia suspected in fatal flu cluster

Lisa Schnirring Staff Writer

Mar 8, 2012 (CIDRAP News) – Another family member linked to a fatal flu cluster in Calvert County, Md., has been hospitalized, as suspicion grew that an aggressive drug-resistant form of pneumonia may have played a role in the severe illnesses, according to media reports.

 

Maryland and Calvert County health officials didn't report any new details about the cases, but the Washington Post reported yesterday that the sister of the 81-year-old woman who died has been hospitalized at MedStar Washington Hospital Center with fever but no other flu symptoms.

(Continue . . . )

 

 

Tissues taken during autopsies from two of the victims have reportedly been sent to the CDC for further analysis, which can take a day or two to complete.

Vietnam:`New’ H3N2 Swine Flu Virus Reported

 

UPDATED: 1500hrs

Henry Niman has posted this afternoon that after further review, he believes this report to be a badly translated repost of a story from December on 10 Cases in the United States we already knew about. 

Today’s story is ambiguous enough to make that a plausible explanation.   Unless and until we can get some confirmation of this story I would advise that you view the following report with caution.

 

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This morning Editor & Senior Moderator Tetano on FluTrackers has picked up a series of news articles coming out of Vietnam talking about 10 human cases of infection by a `new’ H3N2 swine flu virus.

 

Two of these articles are machine translated from Vietnamese, and are therefore a bit garbled, but the third is an English Language report from the VOV (Voice of Vietnam). 

 

Assuming the major points of today’s report are correct (not always a given), there is not enough information provided to know how this virus compares to the A/H3N2v virus which has been detected in a handful of cases in the United States (see CDC Releases Updated H3N2v Interim Guidance).

 

Keeping the usual caveats in mind regarding early media reports, here is the story from the Voice of Vietnam.

 

 

New strain of swine flu detected

Updated : 5:16 PM, 09/02/2012

(VOV) - The Heath Ministry has quoted sources from the Ho Chi Minh City Pasteur Institute confirming that a new kind of porcine flu virus, A/H3N1, has appeared, apparently a combination of the pig-related A/H1N1 and A/H3N2 flu viruses.

 

The medical sector has monitored 10 patients infected with the A/H3N2 virus with porcine origin, and found that three of them had not had direct contact with any diseased pigs.

 

Therefore, the sector has not ruled out the possibility of a mutation in the A/H3N2 strain which could lead to transmission between humans, instead of strictly from pigs to humans as previously.

 

However, the situation has not reached an alarming level because the virus has not changed much; it has low toxicity and has shown no sign of drug resistance.

 

Flu vaccines are able to cope with small changes in this kind of virus, said Le Hoang San, Vice Director of the HCMC Pasteur Institute.

 

 

Swine are highly susceptible to the influenza virus, and are capable of serving as `mixing vessels’, allowing them to reassort into new hybrid strains.

 

Reassortment happens when two different influenza viruses co-infect the same host, swap genetic material, and produce a hybrid virus. 

 

That is essentially what happened in 2009, when the H1N1 swine flu virus emerged after bouncing around swine herds for a decade or more, picking up genetic changes along the way.

 

And not surprisingly, this recently emergent `humanized’  H1N1 virus has re-entered the swine population and is once again mixing and matching with other circulating swine flu viruses.

 

As a result we now have a Swine H3N2 virus that has reassorted with the 2009 pandemic H1N1 virus, producing a new hybrid that has – in a limited fashion – begun to emerge into the human population.

 

The article above calls the Vietnamese strain a `combination of the pig-related A/H1N1 and A/H3N2 flu viruses’ – which if we take literally – suggests a different reassortment than the one we’ve seen in the United States.

 

 

As stories in the media often gloss over or confuse crucial scientific details we really need to wait for a more definitive report before we can talk about the origin, genetic makeup, and potential of this new virus.

 

For now, this is simply something new to keep an eye on in the ever changing and always surprising world of influenza.

 

Update:  In a conversation with Sharon Sanders of FluTrackers this morning, she pointed out that this article refers to this new reassortant virus as H3N1 (once) and H3N2 (twice).

I took the first mention (H3N1) as a likely misprint, but until we can get some clarification, I don’t think we can say with any confidence exactly which strain this new virus is.

New England Seal Deaths Tied to H3N8 Flu Virus

 

 

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We’ve a follow up from NOAA today on the mysterious deaths of seals along the New England coastline earlier this fall.  In early November I reported (see NOAA: New England Dead Seals Test Positive For Flu) that initial tests indicated an influenza A virus, but more testing was needed to determine the exact strain.

In the past, we’ve seen rare and isolated influenza infections resulting in seal deaths from the H7N7 and H4N5 avian flu viruses.

 

Today we learn that the viral culprit in this latest incident is a variant of the H3N8 avian flu strain, versions of which are known to also infect horses and dogs.

 

My thanks to @JustinNOAA for the link to this news release.

 

 

Science team identifies influenza virus subtype that infected five dead seals

Risk to humans and pets low; tests continue

PDF/Print version

Harbor Seals (Credit NOAA)

A virus similar to one found in birds but never before in harbor seals was the cause of five of 162 recent deaths of the animals  in New England, according to a group of federal agencies and private partners.

 

This Influenza A virus subtype, H3N8, appears to have a low risk of transmission to humans. Experts continue to analyze this virus, and any findings of public health significance will be immediately released. The virus is not the infamous H5N1  virus that caused a global pandemic in 2007, or the H1N1 virus from 2009.

 

Any member of the public who sees a seal in distress is reminded to:

• Stay at least 150 feet away
• Keep dogs leashed and away from seals
• Call NOAA Fisheries Service's stranding hotline at 1-866-755-NOAA (6622)

“The work that NOAA and its partners have done to help identify and confirm the virus strain H3N8 in these animals has been an important first step in the investigation into this event,” said Dr. Teri Rowles, lead veterinarian and coordinator of the Marine Mammal Health and Stranding Program for NOAA Fisheries Service. “We are now conducting tests on additional animals to learn more about the role this virus may have played in the die-off and to better understand the virus itself.”

 

Experts believe that Influenza A virus caused a bacterial pneumonia which was responsible for the death of the five seals. Most terrestrial animals infected with the previously known H3N8 virus suffered upper respiratory infections, and most recovered.

 

"This H3N8 virus is usually associated with wild birds, and a separate group of H3N8 infects horses and dogs,” said Dr. Hon Ip, of the USGS’s National Wildlife Health Center. "This is the first time that a virus which is similar to the H3N8 avian influenza virus has been associated with a large scale mortality in marine mammals."

(Continue . . . )

Hong Kong: Swine Influenza Surveillance

 

 

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According to the FAO, the world produces somewhere on the order of 100 million tonnes of pork every year, and that number is expected to increase by another 20% by 2020.

 

By then, roughly half of the world’s pork supply will come from China (cite).

 

Swine are highly susceptible to the influenza virus, and are capable of serving as `mixing vessels’, allowing them to reassort into new hybrid strains.

 

Reassortment happens when two different influenza viruses co-infect the same host, swap genetic material, and produce a hybrid virus. 

 

That is essentially what happened in 2009, when the H1N1 swine flu virus emerged after bouncing around swine herds for a decade or more, picking up genetic changes along the way.

 

And not surprisingly, this recently emergent `humanized’  H1N1 virus has re-entered the swine population and is once again mixing and matching with other circulating swine flu viruses.

 

In recent months we’ve been following reports of a handful of sporadic human infections across three states (Indiana, Pennsylvania, Maine) by a swine H3N2 virus that has reassorted with – and borrowed the M gene segment from – the pandemic H1N1 virus.

 

So far, the number of cases is small, and the CDC states there is no evidence that this emerging hybrid virus is spreading in an efficient or sustained manner. But the concern is, that over time it might evolve into a more human-adapted virus.

 

For some recent coverage of these trH3N2 cases, you may wish to revisit:

 

CDC Update On trH3N2 Swine Infections

Maine Confirms A 2nd trH3N2 Case

CDC Update On trH3N2 Cases

A 5th trH3N2 SOIV Report

CDC Update On Recent Novel Swine Flu Cases

MMWR: Swine-Origin Influenza A (H3N2) Virus Infection in Two Children

 

Given the potential for the creation and emergence of novel influenza viruses, surprisingly little testing and surveillance of pigs takes place around the world. 

 

Even in the U.S. some hog farmers are reluctant to allow their herds to be tested (see Swine Flu: Don’t Test, Don’t Tell) out of fears that the discovery of a new swine flu virus would depress pork sales.

 

As might be expected, Hong Kong - which was the first battleground for the H5N1 bird flu virus in 1996, and which had to deal with SARS in 2003 – has a very aggressive surveillance system.

 

Today the HKSAR government has released the latest results from their ongoing slaughterhouse surveillance program conducted by the University of Hong Kong.

 

Between August and mid-October 1,000 pigs were tested, and while no `human H1N1’ viruses were detected,  15 reassorted H3N2 viruses with (unspecified) genetic contributions from the 2009 H1N1 virus were discovered.

 

First, some excerpts from the press release, then I’ll return with a little more.

 

FEHD releases results of regular influenza virus surveillance in pigs from August to October

 

Hong Kong (HKSAR) - The Centre for Food Safety (CFS) of the Food and Environmental Hygiene Department (FEHD) today (November 16) announced results of the regular influenza virus surveillance programme on pigs conducted by the University of Hong Kong (HKU) for August to mid October at the Sheung Shui Slaughterhouse.

 

Among some 1 000 samples tested, no human swine influenza virus (pandemic H1N1) was detected. However, 15 samples were found to contain a virus that was essentially a swine influenza H3N2 virus but had picked up some genes of human swine influenza virus. The same virus was also found in the last round of surveillance programme for May to July.

 

The HKU expert in charge of the surveillance programme,professor JSM Peiris, reiterated that this swine influenza H3N2 virus, which carried the genes of the human swine influenza virus, is unlikely cause any major human health risk or problems in food safety.

 

Under the regular influenza virus surveillance programme for pigs, the CFS has been helping HKU researchers to collect blood and tracheal and nasal swabs from pigs at the Sheung Shui Slaughterhouse twice a month to monitor influenza virus activity in pigs.

 

"CFS will continue to monitor reports of the HKU surveillance programme and make announcements on a regular basis. Results will be announced immediately if there are significant public health impacts," the spokesman said.

(Continue . . .)

 

 

While this report describes these reassorted swine H3N2 viruses as having `picked up some genes of human swine influenza virus’, it provides no further details. 

 

It would be of interest to see just how closely related these reassorted viruses are to the trH3N2 isolates that have recently been detected in the United States over the past few months.

 

Hopefully we’ll get a more specific description of these H3N2 reassortants over time.

 

For now, and until such time that these reassortants evolve to become more easily transmissible among humans, they pose a relatively low public health threat.

 

While it is always possible that the next pandemic will emerge from the wild, the odds say it will come from a farm – where large numbers of animals intermingle, swap viruses, and come in daily contact with humans.

 

Which is why increasing our surveillance of livestock for zoonotic diseases must become a priority.

 

Over the past 5 years, we’ve revisited the subject of influenza reassortment dozens of times.   For more on this topic, you may wish to visit:

 

Virology Journal: Receptor Cells In Minor Poultry Species

mBio: A/H1N1 Potential For Mutation

Study: The Continuing Evolution Of Avian H9N2

EID Journal: Co-Infection By Influenza Strains

EID Journal: Swine Flu Reassortants In Pigs

If You’ve Seen One Triple Reassortant Swine Flu Virus . . .

 

And as always, if you have not already read it, I highly recommend Helen Branswell’s Scientific American article called Flu Factories.

An Influenza Double Whammy

 

 

 

# 5936

 

 

Although we’ve seen this sort of thing a few times before, the news yesterday that researchers in Cambodia detected two patients with dual influenza infections (back in 2009) has made quite a splash in the media overnight.

 

Some of the headlines include:

 

It's Possible to Come Down With Two Flu Viruses at Once Yahoo! 

Cambodians infected with both swine, seasonal flu The Straits Times

Global flu watch: Report of rare flu coinfection in Southeast Asia hot... PhysOrg.com

 

Like the influenza virus itself, the UK papers tend to go for the throat with their headlines:

 

Britain On Alert For New Super-flu Daily and Sunday Express

Deadly strain of super-flu 'could spread to Britain within 24 hours' Daily Mail

 

 

Before these hyperbolic headlines entice anyone to head down to the bunker, the study on which these stories are based found no `super flu’.

 

In fact, while researchers detected a relatively rare dual infection of seasonal H3N2 and the new pandemic H1N1 virus in a pair of Cambodian patients, in neither case did they find a reassortant virus.

 

The point is, this is the sort of set up that could have produced a new, potentially dangerous hybrid virus.

 

First stop, the study which appears in the American Journal of Tropical Medicine & Hygiene, then we’ll come back and look at the potential ramifications of dual influenza infections.

 

Dual Infection of Novel Influenza Viruses A/H1N1 and A/H3N2 in a Cluster of Cambodian Patients

Christopher A. Myers, Matthew R. Kasper, Chadwick Y. Yasuda, Chin Savuth, David J. Spiro, Rebecca Halpin, Dennis J. Faix, Robert Coon, Shannon D. Putnam, Thomas F. Wierzba and Patrick J. Blair

 

 

The details are behind a pay wall, but as the authors point out in their abstract:

 

This incident confirms dual influenza virus infections and highlights the risk of zoonotic and seasonal influenza viruses to coinfect and possibly, reassort where they cocirculate.

 

 

Earlier this year you may recall we saw a similar co-infection in Canada that actually led to the creation of a unique hybrid reassorted virus (see Webinar: pH1N1 – H3N2 A Novel Influenza Reassortment).

 

In this case, the patient was a 16-month old boy from the Greater Toronto Area who was admitted briefly to a local hospital for respiratory and gastrointestinal symptoms in January of 2011.

 

The child was sent home, and recovered without incident, and no other family members or contacts reported flu-like symptoms.

 

It wasn’t until later, when viral cultures showed a hybrid (reassorted) H1N1-H3N2 virus, did scientists realize that something unusual had occurred.

 

Details of this event were presented in an online webinar on June 16th of this year. 

 

From the abstract:

 

pH1N1 – H3N2: A Novel Influenza Virus Reassortment

Presenter:

Dr. Jonathan Gubbay- Medical Microbiologist, OAHPP

Abstract

Dr. Jonathan Gubbay, medical microbiologist at the Toronto Public Health Laboratory, will present on a new influenza virus that has been discovered by the Ontario Agency for Health Protection and Promotion (OAHPP). It is the first Canadian confirmed finding of a patient with a coinfection of seasonal H3N2 and pH1N1 followed by reassortment.

(Continue . . .)

 

A little more than a year ago, in EID Journal: Co-Infection By Influenza Strains, I wrote about a study in New Zealand during the opening months of the 2009 pandemic that discovered at least 11 co-infections (out of 1,044 samples tested) with the older seasonal H1N1 virus and the newly emergent pandemic H1N1 virus.

 

Pandemic (H1N1) 2009 and Seasonal Influenza A (H1N1) Co-infection, New Zealand, 2009

Matthew Peacey , Richard J. Hall, Stephanie Sonnberg, Mariette Ducatez, Shevaun Paine, Mackenzie Nicol, Jacqui C. Ralston, Don Bandaranayake, Virginia Hope, Richard J. Webby, and Sue Huang

 

 

The authors state that the rate of co-infection could actually be higher, since samples were not checked for any other flu strains such as H3N2 and influenza B.

 

And going back even further, Maryn McKenna wrote – in an article for CIDRAP News – of an Indonesian teen who was found to have been co-infected with an avian (H5N1) and a human (H3N2) influenza strain.

 

Avian, human flu coinfection reported in Indonesian teen

Maryn McKenna Contributing Writer

Mar 17, 2008 – ATLANTA (CIDRAP News) – An Indonesian teenager has been brought forward as a case of simultaneous infection with seasonal and avian strains of influenza—a possibility that health planners have long warned could give rise to a pandemic flu strain.

(Continue . . . )

 

In the Indonesian and New Zealand cases above, no reassortant viruses were detected. Still, this research suggests that humans, like swine, could be `mixing vessels’ for influenza. 

 

While gene swapping is possible under a co-infection scenario, it isn’t by any means assured.

 

And even should a reassortment take place, the resulting virus might not prove biologically `fit’, or if it is `fit’, any worse than either of its parental strains.

 

However, the potential for creating a devastating novel flu strain cannot be discounted.

 

Last August, in Professor Peter Doherty On Bird Flu, we looked at his worries on the possibility that the H5N1 virus might one day swap genes (reassort) with the H1N1 virus and produce an easily transmitted, highly virulent flu strain.

 

And in September we saw research (see Study: Reassorted H1N1-H5N1 Produced Virulent Strain) where a laboratory-created reassortant virus with genes taken from the H5N1 and H1N1 virus produced a highly transmissible and virulent strain.

 

Of course, while the world was waiting for bird flu, in 2009 a reassorted Swine flu virus unexpectedly sparked a global pandemic. We were fortunate that it wasn’t any more severe than it was, but it illustrates that there are many ways a pandemic can evolve.

 

 

In addition to the various clades of human flu strains ( both pdmH1N1 & H3N2) now circulating, and a growing constellation of avian flu strains (H5N1, H9N2, H7N7, etc), we continue to see rare sporadic human infections by reassorted swine viruses as well (Maine Confirms A 2nd trH3N2 Case).

 

Further evidence that nature’s laboratory is open 24/7, and that influenza viruses are constantly mutating and reassorting, looking for an evolutionary advantage.

 

While most of these reassortant viruses are doomed to end up in the evolutionary dustbin, failing to thrive and compete with other viruses, it only takes one fit, virulent, and easily transmissible virus to spark a global pandemic.

 

And that is something that might emerge tomorrow, next month, or perhaps not until years from now.  

 

But history as history has us shown over and over:

 

Pandemics happen.  Count on it.

Pennsylvania DOH: Updated FAQ On The Novel Swine Flu Cluster

 

 

 

# 5818

 

 

The Pennsylvania Department of Health has updated their FAQ sheet (Q & A: Novel Influenza A Virus) on the recent detections of a reassorted H3N2 swine flu virus in three children who attended a county fair in mid-August.

 

It is still very early in the epidemiological investigation of these cases, and there are a lot of questions yet to be answered.

 

Prime among those is whether this virus has the potential to spread efficiently in humans.

 

For now, evidence of sustained human transmission has not been found.  Of course, the CDC is still investigating, and that could change if more cases show up.

 

But it is important to note, that even if a few more cases were to show up over the next few weeks, that wouldn’t necessarily mean that we are faced with an epidemic or pandemic situation. 

 

For that to happen the virus would need to be adapted well enough to human physiology to have an R₀ number (basic reproductive number) sufficient to sustain an outbreak.

 

The R₀  number signifies the average number of secondary infections caused by one infectious person entering a totally susceptible population. 

 

If less than 1.0, outbreaks are likely to sputter and die out.  If greater than 1.0, the outbreak is more capable of spreading. 

 

And as we’ve seen with roughly 20 other reported novel swine infections since 2005, and with a significant number of H5, H7, and H9 avian flu infections, it is possible to have limited outbreaks of a novel flu virus without it sparking an epidemic.

 

We’ll need to wait for more epidemiological evidence before we can know whether this particular virus has `legs’. If it is spreading efficiently (and that’s still a big `if’), we ought to see evidence of that fairly soon.

 

It is also possible that if this virus isn’t ready for prime time right now, that through further reassortment or mutation, it could become better adapted down the road. The only constant with influenza viruses is change.

 

So this situation deserves ongoing surveillance.

 

But regardless of this virus’s fate, the risks of seeing another novel pandemic virus emerge sometime in the future from either the farm or the wild are genuine.

 

 

A few recent blogs on this possibility include:

 

Professor Peter Doherty On Bird Flu

Two Reassortment Studies To Ponder

Hong Kong: Influenza Surveillance In Pigs

The (Swine) Influenza Reassortment Puzzle

 

 

The CDC’s investigation into these recent novel flu cases in Pennsylvania continues, and hopefully we’ll know more shortly.

 

Below are some excerpts from yesterday’s (9/6/11) updated Health Department FAQ. 

 

 

Questions & Answers: Novel Influenza A Virus

 
About the Flu Virus/Current Vaccination 

• 

What is this novel influenza A virus? 
Influenza A viruses occur in many animals, including humans, swine (pigs) and wild birds.This particular virus is unique from other previous H3N2 human infections in that it also contains a genetic piece of the 2009 H1N1 virus.

  
• Is it possible for humans to transmit it to other humans?  
Currently, it does not appear the virus is spreading from person‐to‐person.  However, we will continue to learn ore as our investigation into this new virus continues.  

•

How serious is this virus?  
We currently know of three cases of this novel influenza virus. One patient has recovered and the other two are recovering. Our investigation will continue to focus on the seriousness of the virus.  Based on what we know about other types of flu, illness can range from very mild symptoms to death in particularly susceptible populations (like older people, young children and those with certain medical conditions).

 

•  What does this mean for this year’s flu vaccines? Will the current vaccine cover both seasonal flu and this new strain of flu?  
The 2011‐2012 vaccine is the same as last year, covering two strains of influenza A pandemic H1N1 and a H3N2 strain that has been circulating for a few years now) as well as a strain of influenza B.  It is too early to tell whether or not this new strain will even need vaccination.  

<SNIP>

Should we be concerned that a flu pandemic is pending?  

A pandemic is a global outbreak of disease.  A flu pandemic happens when a new strain of the flu virus appears for which people have little or no immunity. As a result, it spreads easily from person to person around the world, causing widespread illness and death.

 

Currently, we don’t have any evidence to support that this novel influenza A virus will lead to a pandemic, as we haven’t yet been able to prove that it is being transmitted from human to human.

 

As with any new influenza A virus, public health officials  are working to learn more about the source of this particular strain and to determine how/if it can be spread from person to person. 

M Is For Mutation

 

 

 

# 5812

 

 

I usually try to avoid using the word `Mutant’ or `Mutation’ in my blog titles about flu because, strictly speaking . . .

 

All influenza viruses are the product of mutation.

 

Flu viruses are inherently unstable (in particularly, influenza A), and are constantly evolving and changing. Mutating. Which explains why scientists must adjust the flu vaccine nearly every year.

 

Of course, the media loves the word `Mutation’ – I suspect because it conjures up vivid images in the minds of their readers. And to the public, mutations are almost universally perceived as `bad’. 

 

Earlier this week we saw a plethora of `Mutant’ headlines, including:

 

New bird flu virus mutation threatens Vietnam -Thanh Nien Daily

No vaccine yet for mutant bird flu ...  - The Straits Times

Mutant Bird-Flu Strain Spreads in Asia - The Daily Beast

Mutant bird flu strain in Asia prompts call for scrutiny - MSNBC

 

 

While the emergence of this (relatively) new strain of H5N1 is a big story, so far we’ve seen no evidence to suggest that this `mutation’ poses any greater threat to humans than do any of the other dozen or so clades of the bird flu virus.

 

But that isn’t the sort of lede that sells newspapers.

 

Since the `M’ word seems to be on the lips of many people this week, today seems like a good day to go over how influenza viruses mutate.

 

Don’t worry. 

 

I’ll keep this layman simple, mostly so I – a non-scientist - can understand it.  Real scientists, however, may wish to avert their eyes.

 

The genetic sequence of the influenza virus can be represented by a chain of letters identifying the hundreds of amino acids that make up the viral genome.

 

A tiny sub-section of that chain might have an amino acid sequence that looks something like:

 

MKAILVVMLYTFATA

 

As the virus inhabits a cell, and begins to replicate, it makes thousands of copies of itself which then burst out of the cell after a few hours and go on to infect other cells.

 

Those cells, in turn, make copies that go forth to infect more cells and repeat the process.

 

But being a single-strand RNA virus, the influenza virus tends to be sloppy in making copies of itself. As it replicates millions of times, tiny errors sometimes creep in. If in the process of making copies it mixes up just a single amino acid, we can end up with a mutated virus.

 

MKAILVVMLYTFATA

MKAILVVMLYTFATA

MKAIFVVMLYTFATA      -  Voila! A mutation

MKAIFVVMLYTFATA

MKAIFVVMLYTFATA

 

Above, I’ve swapped out the amino acid leucine (L) at position 5 for phenylalanine (F), simulating a replication error.

Assuming the result is a `biologically fit’ and competitive virus (most aren’t), then it may go on to infect other cells, and conceivably, other hosts.

 

Of course, that doesn’t mean it will make the virus more dangerous.  A mutation can make the virus less virulent or less transmissible.

 

Or it may simply have no effect at all.

 

These small mutations in the virus are called drift, and over time the flu virus can accumulate enough changes so that last year’s vaccine is no longer effective.

 

And that is essentially the story behind this new 2.3.2.1 clade of the H5N1 virus. Enough antigenic changes have accumulated in its genome to allow it to evade the poultry vaccines currently in use.

 

Of course, mutations like these are also capable of bringing about other changes, including antiviral resistance, or perhaps increasing the virulence or transmissibility of the virus.

 

So while not necessarily alarming, this week’s bird flu news is certainly worthy of our attention.

 

Bigger changes in the influenza virus generally come about through a process known as reassortment or shift.

 

Reassorted viruses can result when two different flu strains inhabit the same host (human or otherwise) at the same time. Under the right conditions, they can swap one or more gene segments and produce a hybrid virus.

 

 

While far less common than drift, shift can produce dramatic changes in how a virus behaves, and has been responsible for the creation of pandemic viruses in the past. 

 

Again this week, we’ve received news of a pair of `reassortant’ swine H3N2 flu viruses detected in children from two different states (see MMWR: Swine-Origin Influenza A (H3N2) Virus Infection in Two Children).

 

For those of us who were covering the earliest reports of a novel swine flu outbreak in April of 2009, this week’s report admittedly has a tinge of deja flu.

 

But it is important to remember that over the past 5 years (excluding the 2009 H1N1 virus) nearly 2 dozen similar novel swine flu viruses have been detected across the country. It is also probable that a number of other novel infections have escaped notice – yet so far none has been shown to spread efficiently from human-to-human.

 

That could change, of course - as each reassortant is  a new roll of the genetic dice - and so the CDC quite understandably is encouraging enhanced local flu surveillance, and would mount a vigorous response if more cases were to start to appear. 

 

Flu viruses have been quietly mutating and reassorting for thousands of years, but only rarely does that result in a pandemic strain. The vast majority of these mutations end up in evolution’s dustbin.

 

Even though we don’t always know what they signify, today we have the surveillance tools that enable us to watch some of these genetic changes when they start to appear.

 

 

And while that means we are likely to hear about a lot of potential viral threats that never materialize, it also means we may get some invaluable advance warning about the next pandemic virus before it strikes. 

Webinar: pH1N1 – H3N2 A Novel Influenza Reassortment

 

 

# 5622

 

Last week we got word of the first detection of a reassortment between the (formerly) pandemic H1N1 virus and a seasonal H3N2 influenza virus, which was announced by researchers in Toronto, Canada.

 

The case involved a  16-month-old boy from the Greater Toronto Area was admitted briefly to a local hospital for respiratory and gastrointestinal symptoms last January.

 

The child was sent home, and recovered without incident, and no other family members or contacts reported flu-like symptoms.

 

It wasn’t until later, when viral cultures showed a hybrid (reassorted) H1N1-H3N2 virus, did scientists realize that something unusual had occurred.

 

It is known that influenza viruses – if they co-infect the same host simultaneously – have the ability to swap genetic segments and form a hybrid.

 

This sort of reassortment can occur in any host; human, porcine, or avian.  

Most of the time, these reassortments are evolutionary dead ends. They are either biologically unfit, or unable to compete with their better adapted parental strains, and fail to reproduce and thrive.

 

On exceedingly rare occasions, they can produce a competitive new virus - and as we saw in 2009 - spark a global pandemic.

 

Since both of the contributor viruses in this case are already widely circulating strains, concerns over this particular reassortment becoming a serious public health threat are slim.

 

But it does highlight the fact that reassortments can, and do, occur. And the importance of enhanced surveillance if we hope to detect the next pandemic flu threat early.

 

You can read a few more details on this case in the following Canadian Press article from last Friday.

 

New flu virus emerges after child co-infected with H1N1, H3N2; vaccine protective

By Sheryl Ubelacker, Health Reporter, The Canadian Press

 

 

On Thursday of next week (June 16th) a free webinar and Teleconference is planned as part of the OAHPP (Ontario Agency for Health Protection and Promotion) Grand Rounds that will provide the latest information and perhaps some additional insight on this reassorted virus.

 

Registration is Free and Easy on the Eventbrite website. 

 

The details from the webinar announcement follow:

 

OAHPP Rounds: pH1N1 – H3N2: A Novel Influenza Virus Reassortment

Thursday, June 16, 2011 from 12:00 PM - 1:00 PM (ET)

Toronto Ont.,

 

Presenter:

Dr. Jonathan Gubbay- Medical Microbiologist, OAHPP

Discussant:

Dr. Natasha Crowcroft- Director, Surveillance and Epidemiology, OAHPP

Abstract

Dr. Jonathan Gubbay, medical microbiologist at the Toronto Public Health Laboratory, will present on a new influenza virus that has been discovered by the Ontario Agency for Health Protection and Promotion (OAHPP). It is the first Canadian confirmed finding of a patient with a coinfection of seasonal H3N2 and pH1N1 followed by reassortment. To the best of our knowledge, this is the first case ever reported globally. The sample was submitted to OAHPP laboratories and testing identified co-infection and reassortment of the two viruses. These results were validated by National Microbiology Laboratory in Winnipeg.

 

The new virus is a hybrid of two viruses currently circulating in humans, both of which are covered by the current seasonal influenza vaccine (the H3N2 virus and the H1N1 virus). There have been no reports of additional cases or human-to-human transmission. Dr. Gubbay will be discussing the above case as well as molecular changes within the seasonal H3N2 influenza that have been seen this season.

 

Dr. Natasha Crowcroft will be the discussant, commenting on the public health significance of this finding.

 

I’ve already registered, and will make every attempt to attend via the webinar. 

EID Journal: H1N1 Reassortment Possibilities

 

 

# 5255

 

 

The only constant about flu viruses is that they are always changing. Among the world’s viruses, influenza are some of the most adept at reinventing themselves in order to get around mankind’s acquired immunity.  

 

Since influenza strains spread amazingly well, herd immunity can build rapidly.  Without the ability to evade this immunity, influenza viruses would soon run out of susceptible hosts.

 

The two methods that influenza viruses use to evolve are antigenic drift (small mutations, sometimes single amino acid substitutions) and antigenic shift (large, often dramatic changes due to viral reassortment).

 

Drift happens slowly, and incrementally, and is the reason why the flu vaccine must be updated and changed every year or two.  

 

Shift, or reassortment, happens abruptly when two different influenza viruses co-infect the same host and swap genetic material.

 

 

Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).

 

Which means that any two compatible influenza viruses could conceivably – and under the right conditions – generate more than 250 different combinations by swapping one or more of their 8 (potentially) interchangeable gene segments.

 

The key words being “under the right conditions”.

 

If it were easy, or a common occurrence, we’d be up to our hip boots in new, reassorted viruses all the time.

 

But it happens often enough that we recognize it as a real threat.   Shift is how new pandemic strains are born, and it was precisely the mechanism that created the 2009 `swine’ flu strain.

 

Which brings us to a new study, which appears today in the CDC’s EID Journal, that looks at the potential for the 2009 H1N1 virus to reassort with other currently circulating flu viruses and create a more virulent flu strain.

 

You’ll, no doubt, recognize some of the authors of this paper, notably Ab Osterhaus and Ron Fouchier. I’ve reproduced the link, and the abstract (slightly reformatted for readability) below.

 

Volume 17, Number 2–February 2011

Research

Possible Increased Pathogenicity of Pandemic (H1N1) 2009 Influenza Virus upon Reassortment

 

Eefje J.A. Schrauwen, Sander Herfst, Salin Chutinimitkul, Theo M. Bestebroer, Guus F. Rimmelzwaan, Albert D.M.E. Osterhaus, Thijs Kuiken, and Ron A.M. Fouchier

Abstract

Since emergence of the pandemic (H1N1) 2009 virus in April 2009, three influenza A viruses—seasonal (H3N2), seasonal (H1N1), and pandemic (H1N1) 2009—have circulated in humans. Genetic reassortment between these viruses could result in enhanced pathogenicity.

 

We compared 4 reassortant viruses with favorable in vitro replication properties with the wild-type pandemic (H1N1) 2009 virus with respect to replication kinetics in vitro and pathogenicity and transmission in ferrets.

 

Pandemic (H1N1) 2009 viruses containing basic polymerase 2 alone or in combination with acidic polymerase of seasonal (H1N1) virus were attenuated in ferrets.

 

In contrast, pandemic (H1N1) 2009 with neuraminidase of seasonal (H3N2) virus resulted in increased virus replication and more severe pulmonary lesions.

 

The data show that pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza viruses, which may result in increased pathogenicity while it maintains the capacity of transmission through aerosols or respiratory droplets.

 

 

Since you could wait a very long time indeed for reassortments like these to occur naturally - in order to study them – man made flu viruses must be created in the laboratory using reverse genetics.

 

To simplify matters, these researchers only looked at four laboratory generated reassortments out hundreds of possible combinations, selecting those that replicated well in vitro. 

 

While some of these hybrid viruses were weaker that the original 2009 H1N1 virus, reassortants incorporating the NA (neuraminidase) gene from the seasonal H3N2 virus proved more pathogenic (at least in ferrets).

 

All of these tested reassortants retained `biological fitness’ and could be transmitted among ferrets through aerosol or respiratory droplets.

 

The authors state:

 

We conclude that the pandemic (H1N1) 2009 virus has the potential to reassort with seasonal influenza virus A (H1N1) and influenza virus A (H3N2) and that such reassortment events could result in viruses with increased pathogenicity in ferrets.

 

Although increased pathogenicity in ferrets cannot be extrapolated directly to increased pathogenicity in humans, ferrets are susceptible to natural infection and respiratory disease and lung pathology develop in a manner similar to that in humans infected with seasonal, avian, or pandemic influenza viruses.

 

 

Follow the above link to read about how the tests were conducted, some of the limitations on these sorts of experiments, and additional details on the results.

 

If all of this sound vaguely familiar, last November we saw another study (see  mBio: A/H1N1 Potential For Mutation) that looked at the potential for the 2009 H1N1 virus to become more pathogenic through the more common process; antigenic `drift’.

Their conclusion read, in part:

We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.

 

 

While both of these studies point to the potential for the 2009 H1N1 virus to either drift or shift to a more virulent strain, when – or even if – that might ever happen is impossible to say.

 

But they do serve as reminders of how quickly flu strains can change, and of the pressing need to increase our global surveillance capabilities so that we can spot these emerging strains as early as possible.