Influenza Virus Mashup

(Sun, 03 Jul 2011 12:21:00 +0000)

# 5669

Many of the common illnesses we think of as `human’ diseases actually began in other species, and only later migrated to humans. The age of emerging infectious diseases in humans really began in earnest about 10,000 years ago when man began to domesticate – and live in close proximity to – other animals.   

• The scourge of Tuberculosis, which now infects 1/3rd of humanity, probably jumped to humans when man began to coral and raise its traditional hosts; goats and cattle.
• Measles appears to have evolved from canine distemper and/or the Rinderpest virus of cattle.  
• Influenza, as most of you know, is native to aquatic birds – but jumped species thousands of years ago and many strains have adapted to humans, pigs, and other species.

The list of zoonotic diseases (those shared between humans and animals) is long and continually expanding, and includes: SARS, Babesiosis, Borrelia (Lyme), Nipah, Hendra, Malaria, Hantavirus, Ebola, Bartonella, Leptospirosis, Q-Fever, bird flu and many, many others.

Yet despite these disease overlaps, viruses generally adapt to a fairly narrow range of species. 

Horse viruses generally attack equines, and not say, cats and dogs.   Cat viruses tend to attack felines, and not birds.  Bird viruses usually only infect avian species.

 

The species that a virus will infect is known as its host range.  And while usually limited, it isn’t always the case.

Rabies is a good example of a virus that can infect an extraordinarily wide range of species.

We know that every once in awhile, viruses will suddenly jump to a new species. A couple of recent examples include:

The H5N1 bird flu virus, which has been unusually promiscuous: showing up in cats (including tigers), dogs, martens, civets, and of course humans. Researchers have successfully infected cattle with the H5N1 virus, along with ferrets and mice for testing.

 

H3N8 Canine influenza, which only showed up in dogs in 2004, had been known to infect horses for the past 40 years.

 

All of which serves as prelude to a report that appears in the latest edition of the Journal of General Virology, that finds a recently emerged canine H3N2 influenza virus common in Korea has now adapted to infect domestic cats.

Interspecies transmission of the canine influenza H3N2 virus to domestic cats in South Korea, 2010

D.S. Song, D.J. An, H.J. Moon, M.J. Yeom, H.Y. Jung, W.S. Jung, S.J. Park, H.K. Kim, S.Y. Han, J.S. Oh, B.K. Park, J.K. Kim, H. Poo, R.G. Webster, K. Jung and B.K. Kang

Abstract

In the last 4 years, incidences of endemic or epidemic respiratory diseases associated with canine influenza H3N2 virus in Asian dogs have been reported in countries such as South Korea and China. Canine species were considered to be the new natural hosts for this virus.

However, at the beginning of 2010, influenza-like respiratory signs, such as dyspnea, were also observed among cats as well as in dogs in an animal shelter located at Seoul, South Korea. The affected cats showed 100% morbidity and 40% mortality.

We were able to isolate a virus from the lung specimen of a dead cat that had suffered from the respiratory disease, in embryonated chicken eggs. The 8 viral genes isolated were almost identical to those of the canine influenza H3N2 virus suggesting interspecies transmission of canine influenza H3N2 virus to the cat.

Moreover, 3 domestic cats infected with intranasal canine/Korea/GCVP01/07 (H3N2) all showed elevated rectal temperatures, nasal virus shedding, and severe pulmonary lesions, such as suppurative bronchopneumonia.

Our study for the first time shows that cats are susceptible to canine influenza H3N2 infection, suggesting that cats may play an intermediate host role in transmitting the H3N2 virus among feline and canine species, which could lead to the endemic establishment of the virus in companion animals.

Such a scenario raises a public health concern, as the possibility of the emergence of new recombinant feline or canine influenza viruses in companion animals with the potential to act as zoonotic infection cannot be excluded.

The canine H3N2 virus only just appeared in Korea in 2007, and unlike the canine H3N8 virus seen in the United States, appears to have jumped directly from an avian source.

In 2008 the CDC’s EID Journal carried the following report on this newly emerging canine flu.

Transmission of Avian Influenza Virus (H3N2) to Dogs

Daesub Song, Bokyu Kang, Chulseung Lee, Kwonil Jung, Gunwoo Ha, Dongseok Kang, Seongjun Park, Bongkyun Park, and Jinsik Oh

Abstract

In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease.

 

To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) isolate. The beagles shed virus through nasal excretion, seroconverted, and became ill with severe necrotizing tracheobronchitis and bronchioalveolitis with accompanying clinical signs (e.g., high fever).

Consistent with histologic observation of lung lesions, large amounts of avian influenza virus binding receptor (SAα 2,3-gal) were identified in canine tracheal, bronchial, and bronchiolar epithelial cells, which suggests potential for direct transmission of avian influenza virus (H3N2) from poultry to dogs.

Our data provide evidence that dogs may play a role in interspecies transmission and spread of influenza virus.

The good news is that so far, these new canine viruses haven’t shown the ability to infect humans. 

But as the author’s of the EID study above point out:

Transmission of avian influenza A virus to a new mammalian species is of great concern, because it potentially allows the virus to adapt to a new mammalian host, cross new species barriers, and acquire pandemic potential.

Companion animals, such as dogs and cats, are of particular concern because of how closely humans interact with them.

While pigs might be biologically better suited as a `mixing vessel’ for influenza (see The (Swine) Influenza Reassortment Puzzle), there are far more opportunities for transmission between humans and their pets.

In terms of their potential to spread rapidly among humans, and cause significant morbidity and mortality, few viruses can compete with influenza. As we saw in 2009, a new influenza virus can jump species and spread around the globe in a matter of months.

A recurring theme in this blog is that nature’s bio lab is open 24/7, and that it is constantly trying out new genetic combinations looking for an evolutionary advantage. 

 

And for a virus, jumping to a new, immunologically naive species is like hitting the jackpot; a fresh supply of hosts and an opportunity to adapt further.

Which is why we watch these species jumps with more than a passing interest.

(Sat, 02 Jul 2011 12:23:00 +0000)

# 5668

Although we talk about four main strains of influenza that circulate in humans (A/H1N1(pdm), A/H3N2, B Victoria, B Yamagata) – in reality there is a good deal more diversity in flu strains than that.

Influenza viruses are notoriously unstable, mutating at a rapid pace in order to evade acquired immunity. So it isn’t unusual to find numerous genetic variations within the same strain.

In fact, within the same host, you’ll find mutations occurring as the virus replicates. Most go nowhere, being unable to compete with its more `biologically fit’ parental viruses.

But occasionally a competitive strain emerges and crowds out the others, and under the right conditions, can be transmitted to others.

So over time, multiple variations of a virus strain end up circulating simultaneously.

Eventually, these mutations can move the virus far enough away from the original so that existing host defenses are no longer able to recognize it. That reduces (or eliminates) the immunity acquired by previous exposure or vaccination.

When a strain is said to be `antigenically similar’  to the vaccine strain, it is expected (but not assured) that the vaccine remains reasonably effective.  

But as these genetic changes accumulate, the effectiveness of a vaccine may eventually erode, and the vaccine strains must be replaced.

All of this is part of the normal evolution of influenza viruses, known as antigenic drift. It explains why it is necessary to re-evaluate, and change, the flu vaccine every year or two.

This constant reshuffling of influenza genes requires constant ongoing surveillance if vaccine manufacturers are to keep up with the virus. 

Which brings us to the latest ECDC influenza surveillance report for Europe. As you will see, there is a growing diversity in both the H1N1(pdm) and H3N2 virus strains.

First the abstract, and a link to the report:

Influenza virus characterisation, summary Europe, May-June 2011

Technical reports - 30 Jun 2011

 

ABSTRACT

Influenza A(H1N1)pdm, influenza A(H3N2), and influenza B/Victoria/2/87 lineage viruses have been characterised genetically and antigenically.

• Recently isolated A(H1N1)pdm viruses continue to fall into several genetic groups but all groups show antigenic similarity to the currently recommended vaccine virus A/California/7/2009.
• A(H3N2) viruses also continue to fall into distinct genetic groups with some viruses showing antigenic difference from the currently used vaccine virus A/Perth/16/2009, but there is no consistent correlation of altered antigenicity with any genetic group.
• Influenza B viruses of the B/Victoria/2/87 lineage have predominated over those of the B/Yamagata/2/87 lineage. Most of the B/Victoria/2/87 lineage viruses are genetically and antigenically similar to the currently recommended vaccine virus B/Brisbane/60/2008.

After analyzing 450 virus samples submitted by EU countries between January and the end of May, the WHO reference laboratory in London has found the A/H1N1(pdm) strain has divided into 6 main genetic groups.

1. N125D, observed originally as an emerging genetic group in the Southern Hemisphere and subsequently widespread in the Northern Hemisphere and exemplified by the reference virus A/Christchurch/16/2010;
2. D97N and S185T, e.g. A/England/676/2010;
3. S143G, S185T and A197T, e.g. A/Baden-Wurtemburg/14/2010 or A/Brussels/S0004/2011; 
4. A134T and S183P, e.g. A/Alborz/5607/2010; 
5. D97N, R205K, I216V and V249L, e.g. A/Trieste/11/2011;
6. vi)  N31D, S162N (adding a glycosylation site) and A186T, e.g. A/Czech Republic/32/2011

These six groups are increased from four described last April. Despite this growing diversity, the report states:

The majority of viruses continue to react well with the panel of post-infection ferret antisera, including that raised against the vaccine virus A/California/7/2009.

 

Meaning that this fall’s vaccine is still expected to be effective against the bulk of these mutations.

The report shows the H3N2 (seasonal) strain has subdivided into 5 genetic groupings. The first 2 within the A/Perth/16/2009 clade, and the last 3 from the A/Victoria/208/2009  clade.

1. I260M, R261Q, e.g. A/Victoria/210/2009 with some viruses also carrying the substitutions E50K and P162S, e.g. A/Hessen/5/2010;
2. N133D (resulting in the loss of a glycosylation site), R142G, T212A, V213A, e.g. A/Norway/1330/2010
3. N145S and V223I, e.g. A/Cote d’Ivoire/GR1678/2010 with some viruses having the substitution N144D that results in the loss of a glycosylation site, e.g. A/Paris/2120/2010; 
4. N312S, e.g. A/England/270/2010, with many viruses also carrying T48A and K92R, e.g. the reference virus A/Rhode Island/01/2010;
5. D53N, Y94H, I230V, E280A, e.g. the reference virus A/Alabama/05/2010, with some viruses also carrying the substitution S199A, e.g. A/Rheinland-Pfalz/7/2010.

There were a higher number of `low-reactor’ isolates among the H3N2 viruses, but all showed good reactions to A/Wisconsin/15/2009, a virus genetically and antigenically closely related to vaccine strain.

So while the data is a bit murkier on H3N2, there are reasons to believe the vaccine may still be largely effective against those strains as well.

And lastly, among the influenza B samples tested, 80% are a close match to the B/Victoria/2/87 lineage contained in this year’s vaccine.

Laboratory antigen characterization tests can give us an indication of how well a specific vaccine may protect against a virus strain, but they are not 100% predictive.

And admittedly, the viruses that were circulating in the spring may well be different by the fall.

It’s always a bit of a crap shoot when you have to pick just 3 influenza strains - 6 months in advance - to put in your vaccine.

While it may not be possible to cover all of the viral bases with a trivalent vaccine - despite these emerging strains - this year’s vaccine still looks to be a pretty good match for the bulk of the flu viruses now in circulation.

(Sat, 02 Jul 2011 09:08:00 +0000)

# 5667

Most years, July isn’t a big month for Hurricanes in the Atlantic and Caribbean, although in 2005 we saw 3 storms (Cindy, Dennis, Emily) develop in the first half of that month.

Normally, things don’t start to get active until mid-August.  

But this year, the forecast once again is for a very busy season, and so it isn’t too early to be paying attention.

Thus far in 2001 we’ve seen one moderate tropical Storm (Arlene) which impacted the Mexican coast last week, reportedly killing at least 2 people.

According to The National Hurricane Center in Miami, all is quiet right now in the Atlantic tropical basin.

Below you’ll see the the areas that historically have spawned tropical systems in July. 

Unlike later in the year, when we watch for long-track storms to form in the Cape Verde basin, cyclone genesis is more apt to occur in the warmer, shallower waters closer to the United States. 

Over the next several months we are likely to see dozens of areas of suspicion develop in the Atlantic and Caribbean.   Many will likely fizzle . . . but long range forecasts are calling for as many as 18 of these to become named storms, and 6 to 10 to be hurricanes.

How many of those will make landfall is unknown.

Last year (see NOAA 2010 Atlantic Hurricane Outlook) NOAA called for an above average tropical season, and that is exactly what we had, although the coastline of the United States was largely spared.

2010 Hurricane/Storm Tracks

Other years, we aren’t so lucky.

It just takes one major storm to ruin your entire day.

The 1992 hurricane season was particularly quiet, with only 7 storms forming and just two impacting the United States. But one of them was Andrew - the CAT 5 monster that ripped across south Florida.

Which means that if you live anywhere within reach of one of these storms (and that can be hundreds of miles inland), you need to be reviewing your hurricane plans now.

May was National Hurricane Preparedness week, and during that month this blog devoted considerable time to the subject.  A few of my blogs on the subject included:

National Hurricane Preparedness Week 2011

Hurricane Preparedness Week: Inland Flooding

How Not To Be Gone With The Wind

Getting SLOSHed For Hurricane Season

Along with some general preparedness blogs:

When 72 Hours Isn’t Enough

In An Emergency, Who Has Your Back?

An Appropriate Level Of Preparedness

Some essential hurricane resources to get you started include:

http://www.fema.gov/hazard/hurricane/index.shtm

http://www.ready.gov/america/beinformed/hurricanes.html

 

You may also wish to revisit my blog entitled Hurricane Resources On The Net for links to storm resources online.

Via CIDRAP: NEWS SCAN: Poultry safety standards, global flu update, H5N1 vaccine trial, H7N7 outbreaks, European pandemic surveillance, immunomodulator study. Excerpt:

A review of surveillance systems used during the 2009 H1N1 pandemic in 27 European countries found that the systems were resilient and useful, but some countries’ systems had a hard time capturing data on severe respiratory infections. 

The findings were published yesterday in Eurosurveillance. The authors, from the European Centre for Disease Prevention and Control (ECDC), wrote that systems for tracking severe cases and deaths in many cases were introduced during the pandemic, which they said isn’t the best time to launch a new system, because resources are stretched. 

The group also noted that systems for sharing information from the first affected countries could be improved by protecting the security and confidentiality of the communication systems. They also suggested that revised pandemic plans include more seroprevalence studies to provide better information in real time. 

In an accompanying editorial, two public health experts, Dr Heath Kelly of the Victoria Infectious Disease Reference Laboratory in Australia and Dr Benjamin Cowling of Hong Kong University, said early estimates of the reproductive number in the United Kingdom may have been too high, for several reasons. Counting imported cases as locally acquired cases and selection bias could have led to overestimates, they noted. Also, the early estimates included a high proportion of infections in school-age children, a group that had a higher reproductive number than the general population. 

Another factor that could have led to overestimates was unrecognized transmission that occurred prior to testing. The two experts voiced support for the ECDC authors’ surveillance suggestions and said the improvements should be addressed before the next pandemic strikes.

(Fri, 01 Jul 2011 15:44:00 +0000)

# 5666

According to the latest update from the World Health Organization, Influenza levels in the northern hemisphere have returned to inter-season baseline levels, and transmission of flu in the tropics is generally low.

So, for the next few months, it will be activity in the southern hemisphere that will capture our flu interests.

A few excerpts from today’s update follow:

Influenza update - 01 July 2011

Summary

• Influenza activity in the temperate regions of the northern hemisphere is at baseline inter-seasonal levels.

• Transmission in tropical areas is low overall with focal areas of transmission noted in a few countries of Central America and northern South America, western and eastern regions of sub-Saharan Africa, and tropical Asia.

• The influenza season has now started in South Africa and may be starting in Australia as well. South Africa has continued to report increasing numbers of both mild and severe cases, primarily related to influenza A(H1N1)2009. Australia has noted a recent increase in emergency room visits due to influenza-like illness and significantly increased notifications of influenza activity in the states of South Australia and Queensland.

(Continue . . . )

As you can see by the map above, the mix of flu strains varies by region, with influenza B making a stronger appearance in the more tropical zones while influenza A/H1N1 appears to predominate in the more temperate regions.

One trend worth noting is that in Bolivia, influenza A/H3N2 detections have increased steadily for the past 8 weeks. 

South Africa appears to be leading in flu activity, with A/H1N1 (indicated in yellow below) making up the bulk of the samples tested.

Today’s virological analysis states:

The vast majority of recently characterized viruses remain antigenically similar to the WHO recommended vaccines for the 2010-2011 northern hemisphere and 2011 southern hemisphere influenza seasons.

 

During weeks 23 to 24 (05 June 2011 to 18 June 2011), National Influenza Centres (NICs) from 71 countries, areas or territories reported data to FluNet*. A total of 837 specimens were reported as positive for influenza viruses, 583 (69.7%) were typed as influenza A and 254 (30.3%) as influenza B.

Of the sub-typed influenza A viruses reported, 83.2% were influenza A(H1N1)2009 and 16.7% were influenza A(H3N2).

(FluNet data as of 28 June 2011 14:00 UTC)

(Fri, 01 Jul 2011 11:32:00 +0000)

# 5665

NFID is the National Foundation for Infectious Diseases – a non-profit organization founded in 1973 – that describes its mission as: “educating the public and healthcare professionals about the causes, treatment and prevention of infectious diseases.”

NFID is a resource rich website with information fact sheets on a variety of infectious diseases, continuing medical education (CME) links, information on conferences and courses, and publications.

 

While influenza can strike people of any age, it is the elderly who experience the greatest health burden from the illness. Those over 65 are more likely to be hospitalized, or die, as a result of the flu.

(Credit NFID)

The immune system of those over 65 is often  less robust than their younger counterparts, and they may be dealing with underlying chronic conditions such as heart disease, COPD, and diabetes that further increase their risks.

Complicating matters, the influenza vaccine may be less effective in the elderly as well (see Study: Flu Vaccines And The Elderly, Flu Shots For The Elderly May Have Limited Benefits).

Earlier this year NFID convened a panel of experts to address the issues of influenza and the elderly that included such familiar names in public health as Arnold Monto, MD; Kristin Nichol, MD, MPH; H. Keipp Talbot, MD, MPH; and William Schaffner, MD.

From that panel a 5-page brief has emerged, called: Understanding the Challenges and Opportunities in Protecting Older Adults from Influenza.

Although the elderly generally see less protection from the flu vaccine, older individuals may still mount a robust immune response. In populations 65 and older, the brief points out that:

• Hospitalization rates for influenza and pneumonia are lower in community-dwelling adults who received the seasonal influenza vaccine.
• Immunization is associated with reduced hospitalization of older patients for cardiac, respiratory, and cerebrovascular diseases.

While the goal of vaccinating the younger population is to prevent infection, the authors point out that:

. . . the goal in older adults is to prevent severe illness, including exacerbation of underlying conditions, hospitalization, and mortality.

In other words, even if the vaccine doesn’t always prevent infection in the elderly, studies suggest that the vaccine may blunt the seriousness of the illness in those over 65.

The authors also point out that new vaccine technologies are being tested including the new high-dose influenza vaccine (see MMWR On High Dose Flu Vaccine For Seniors, Vaccines: Sometimes You Just Need A Bigger Hammer),  Intradermally administered flu vaccines, and in Europe, the inclusion of adjuvants.

The authors write:

Health care providers should stay alert for the introduction of these new vaccines, learn their benefits for specific populations, and consider all options when planning ahead for the influenza season. In settings with large numbers of frail elderly, such as nursing homes, familiarity with the different options for preventing and managing influenza is especially important.

In addition to embracing universal vaccination for everyone over the age of 6 months and keeping up with the latest technology, the authors urge that health care providers:

Demonstrate a Personal Commitment to Influenza Vaccination

Health care providers can set a good example—and protect themselves and their patients— by receiving the influenza vaccine every year and by encouraging their colleagues and all members of their staff to do so too. Until the health care community as a whole attains a near universal influenza vaccination rate, there is room for much progress to be made in this area.

Although this brief is very brief, it is well footnoted for those who would like to follow up on the statements within.

The bottom line is pretty simple.  Quoting again from the brief:

The public must become aware that influenza is far more serious than the common cold, especially for older people, and that the vaccine is both safe and beneficial.

This brief, along with the other offerings on the NFID site, are well worth taking the time to peruse.

(Thu, 30 Jun 2011 21:33:00 +0000)

# 5564

We’ve a curious report today in the Financial Express – the only English language financial daily in Bangladesh – on the level of bird flu activity in that country.

Since 2007 we’ve often heard of outbreaks of the H5N1 bird flu virus on poultry farms, and the OIE (to whom reporting of H5 & H7 avian flu is mandatory) lists 34 reports totaling 514 outbreaks since May of that year.

(Photo Credit – OIE Bangladesh H5N1)

The last OIE notification was on May 12th of 2011, which noted 3 recent outbreaks,  and the total number of poultry affected since 2007 is listed as just under 640,000.

(Photo Credit – OIE Bangladesh H5N1 Stats)

Which makes the following story in the Financial Express - wherein an Industry leader puts the number of outbreaks at 20 times higher – a bit hard to reconcile.

A hat tip to Carol@SC on the Flu Wiki for this link.

Bird flu wreaks havoc in poultry industry: official

 

Dhaka, Friday July 1 2011

Doulot Akter Mala

A third of the country’s farm-raised chicken has been decimated by the latest outbreak of the bird-flu, a top poultry farmer has said Thursday, demanding compensation for the affected farms.

 

He told the FE the government needed to roll up its sleeve and help the affected farms with compensation and vaccines in an effort to prevent Avian Influenza from inflicting a mortal blow to the key industry.

 

“We’ve estimated that 10,000 to 15,000 poultry firms have been affected by bird-flu. Unfortunately the government shows it only 153,” said Syed Abu Siddique, president of the Bangladesh Poultry Industries Association,

(Continue . . . )

This makes for a sizeable discrepancy between the claims made by the President of the Bangladesh Poultry Industries Association and what has been officially reported to the OIE.

The accuracy of either number is difficult to verify, since the OIE can only report what is voluntarily submitted to them.

And between this report, and others, there is obviously a good deal of political pressure being exerted in Bangladesh over current and future tax breaks for the poultry Industry, compensation for culled birds, and the importation of vaccine.

 

A cause that would be bolstered by higher poultry losses.

There is also the possibility that Siddique is including LPAI outbreaks – such as H9N2 – in his numbers, although only H5N1 is mentioned in the article.

We are left with a bit of a mystery it seems.

And while I am a bit skeptical that 95% of the outbreaks in Bangladesh are going unreported - that country remains one of the hotspots for bird flu activity in the world - and so it deserves our continued attention.