The CDC Recaps The 2014-15 Flu Season

P&I Mortality the past 5 Flu Seasons – Credit FluView

 

 

# 9987

 

With this year’s flu season essentially over in the Northern Hemisphere, it is time once again for the CDC to assess the damage, and as many already know – it was a tough flu year.   Between having an H3 dominated year, and a `drifted’ H3N2 virus that largely evaded this year’s vaccine, the impact was particularly hard on those over the age of 65.

 

2014-15 will go down as the third moderately severe flu season in a row, which followed two comparatively mild seasons (2010-11 & 2011-12), proving you just never know what the next flu season will bring.

 

Yesterday the CDC released the following post-mortem analysis of this latest influenza epidemic season.

 

 

2014-2015 Flu Season Drawing to a Close

April 27, 2015 – Flu activity continues to decline, according to the most recent FluView, which reports that influenza-like-illness (ILI) in the United States has fallen below baseline for the second consecutive week since the middle of November. Other key indicators are declining as well, signaling that the 2014-15 flu season is drawing to a close. The April 24, 2015 FluView covers influenza activity reported from April 12-April 18, 2015.

During the 2014-2015 season, influenza activity started early and had a relatively long duration. Influenza-like-illness (ILI) went above baseline the week ending November 22 and remained elevated for 20 consecutive weeks, making this season slightly longer than average. For the past 13 seasons, influenza-like-illness has been at or above baseline for 13 weeks on average, with a range of 1 week to 19 weeks. The ILI curve for this season is most similar to that from the 2012-2013 season, which is the season during which ILI activity remained above baseline for 19 weeks.

This season was severe for people 65 and older especially. While hospitalization rates are almost always highest among people 65 and older, this season CDC recorded the highest hospitalization rates among this age group since this type of record-keeping began in 2005. People 65 and older accounted for more than 60 percent of all reported hospitalizations and from September 28 through April 18, an estimated 313.8 per 100,000 people in the age group were hospitalized from flu. The next highest recorded hospitalization rate in this age group (182.3 per 100,000) occurred during the 2012-2013 season.

The extremely high hospitalization rate in older adults elevated the overall hospitalization rate for all age groups in the United States to 63.6 per 100,000 people. Hospitalization rates for other age groups were either similar to or lower than what has been seen previously. For example, the age group normally next-most affected by severe illness resulting in hospitalization is children 0-4 years of age. While children in that age group did have the second-highest hospitalization rate this season, that rate through the week ending April 18 (55.4 per 100,000) is lower than what was seen during the same week in 2012-2013 (65.9 per 100,000).

During most of the season influenza A (H3N2) viruses predominated however the country experienced a second wave of influenza B flu activity since early March. Second waves of influenza B activity are common. Seasons during which influenza A (H3N2) viruses predominate typically have higher rates of hospitalizations and more deaths, particularly among older people and children. The last season when H3N2 viruses predominated was in 2012-2013.

Flu-related deaths this season were within expected boundaries for an H3N2 dominant season. CDC monitors flu-related deaths through the 122 Cities Mortality Reporting System, which reports the total number of death certificates processed and the number of those for which pneumonia or influenza is listed as the underlying or contributing cause of death in 122 U.S. cities. Pneumonia and influenza diagnoses (P&I) first rose above the epidemic threshold the week ending January 3, 2015 and peaked the week ending January 17, 2015 at 9.3%. This is comparable to recorded percentages for past severe seasons, including the 2003-04 season when P&I reached 10.4% and the 2012-13 flu season when P&I peaked at 9.9%.

(Continue . .. )

 

Our eyes now turn to the Southern Hemisphere, where the newly formulated flu vaccine is hoped will make a bigger dent in H3N2’s impact this year. But we never really know whether the Southern Hemisphere will be a continuation of our outgoing flu season, or prove to be a harbinger of changes we might see here come the fall.

Global Influenza Update – March 9th

 

# 9802

 

Although it has been a heavily H3N2-centric flu season in North America and most of Europe, as the map above shows, portions of Africa and parts of the Middle and Far East have seen a good deal of seasonal H1N1 (aka A(H1N1)pdm09), which continues to be misrepresented in the press in some nations as `swine flu’ or in some cases `bird flu’.

 

While influenza has peaked across much of the Northern Hemisphere, and is on the decline in North America, some countries are still reporting abundant flu activity.

 

We continue to see hyperbolic press accounts of India’s H1N1 Outbreak, and almost daily suggestions that something `has changed’ with the virus, but so far no evidence has been presented that the virus has altered either its genetic profile or behavior. 

 

Meanwhile, the re-formulated flu vaccine for the next Southern Hemisphere flu season  - which includes the `drifted’ H3N2 strain that has caused considerable illness in the Northern Hemisphere this winter – should be available sometime in April.

 

This from the World Health Organization Global Flu Update.

 

 

Influenza update

9 March 2015 - Update number 232, based on data up to 22 February 2015

Summary

Globally, influenza activity remained high in the northern hemisphere with influenza A(H3N2) viruses predominating. Some countries in Africa, Asia and southern part of Europe reported an increased influenza A(H1N1)pdm09 activity.

• In North America, the influenza activity remained elevated following the influenza peak. Influenza A(H3N2) remained the dominant virus detected this season
• In Europe, the influenza season was at its height, particularly in central and western countries . Influenza A(H3N2) virus continued to predominate this season.
• In northern Africa and the middle East, influenza activity was decreasing in most of the region. Influenza A was predominant in the region.
• In the temperate countries of Asia, influenza activity decreased from its peak in northern China and Mongolia, but continued to increase in the Republic of Korea. Influenza A(H3N2) virus predominated.
• In tropical countries of the Americas, influenza activity remained low in most countries.
• In tropical Asia, influenza activity continued to increase in India and Lao People’s Democratic Republic. Influenza activity remained high in southern China, China Hong Kong Special Administrative Region, and the Islamic Republic of Iran.
• In the southern hemisphere, influenza activity continued at inter-seasonal levels.
• The vaccine recommendation for the 2015-2016 northern hemisphere winter season was made and can be consulted at the link below:
• Based on FluNet reporting (as of 5 March 2015 16:25 UTC), during weeks 6 to 7 (8 February 2015 to 21/02/2015), National Influenza Centres (NICs) and other national influenza laboratories from 89 countries, areas or territories reported data for the time period from 8 to 21 February 2015. The WHO GISRS laboratories tested more than 133 895 specimens. 34 056 were positive for influenza viruses, of which 25 455 (74.7%) were typed as influenza A and 8601 (25.3%) as influenza B. Of the sub-typed seasonal influenza A viruses, 2382 (20.5%) were influenza A(H1N1)pdm09 and 9253 (79.5%) were influenza A(H3N2). Of the characterized B viruses, 1656 (97.1%) belonged to the B-Yamagata lineage and 49 (2.9%) to the B-Victoria lineage.

 

 

FluNet Summary

9 March 2015

Source: Laboratory confirmed data from the Global Influenza Surveillance and Response System (GISRS).

Based on FluNet reporting (as of 5 March 2015, 16:25 UTC), National Influenza Centres (NICs) and other national influenza laboratories from 89 countries, areas or territories reported data for the time period from 8 to 21 February 2015.^a The WHO GISRS laboratories tested more than 133 895 specimens. 34 056 were positive for influenza viruses, of which 25 455 (74.7%) were typed as influenza A and 8601 (25.3%) as influenza B. Of the sub-typed seasonal influenza A viruses, 2382 (20.5%) were influenza A(H1N1)pdm09 and 9253 (79.5%) were influenza A(H3N2). Of the characterized B viruses, 1656 (97.1%) belonged to the B-Yamagata lineage and 49 (2.9%) to the B-Victoria lineage.

• View the full influenza update

Global circulation of influenza viruses
(GISRS-FluNet, snapshot 5 March 2015)

View full size chart
pdf, 359kb

^a The time period from 8 to 21 February 2015 corresponds to

• FluNet / American calendar: weeks 6 and 7
• International standard ISO 8601: weeks 7 and 8

H7N9 In Guangdong, Seasonal Flu In Hong Kong

Credit HK CHP

 

 

# 9721

 

Hong Kong’s CHP has been notified of an additional H7N9 in Guangdong Province, bringing to 54 the number of cases reported from their neighboring province this winter.  Unfortunately, timely reports from the rest of mainland China are in short supply, making it difficult to characterize this year’s outbreak.

17 February 2015

CHP notified of additional human case of avian influenza A(H7N9) in Guangdong 

The Centre for Health Protection (CHP) of the Department of Health (DH) is today (February 17) closely monitoring an additional human case of avian influenza A(H7N9) notified by the Health and Family Planning Commission of Guangdong Province (GDHFPC), and again urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.

According to the GDHFPC, the female patient aged 33 in Guangzhou was hospitalised for treatment in critical condition.

To date, 574 human cases of avian influenza A(H7N9) have been reported by the Mainland health authorities, respectively in Guangdong (163 cases), Zhejiang (156 cases), Jiangsu (70 cases), Fujian (58 cases), Shanghai (45 cases), Hunan (24 cases), Anhui (17 cases), Xinjiang (10 cases), Jiangxi (nine cases), Shandong (six cases), Beijing (five cases), Henan (four cases), Guangxi (three cases), Jilin (two cases), Guizhou (one case) and Hebei (one case).

(Continue . . . )

 

Meanwhile, Hong Kong’s severe flu season continues unabated with daily reports painting a grim picture of both the number of ICU admissions and deaths, with the number of fatal flu cases this winter on track to more than double last year’s total.

 

 

Latest update of surveillance data in winter influenza season

The Centre for Health Protection (CHP) of the Department of Health today (February 17) reported the latest surveillance data of the winter influenza season, and again urged the public to heighten vigilance and get vaccinated early against seasonal influenza.

Regarding severe cases, from noon yesterday (February 16) to noon today, 22 additional cases of influenza-associated admission to intensive care units or death (including 18 deaths) among adults aged 18 or above have been recorded under the enhanced surveillance in collaboration with public and private hospitals reactivated since January 2, bringing the total to 322 (228 deaths) so far. Among them, 306 were A(H3N2), 10 were A pending subtype and six were B. In the last winter season in early 2014, 266 (133 deaths) were filed.

Meanwhile, no additional cases of severe paediatric influenza-associated complication or death among children aged under 18 have been reported since yesterday via the ongoing reporting system and the total this year hence remains at 14 (no deaths) and all were A(H3N2). In 2014, 27 (four deaths) were filed.

(Continue . . .)

This year’s flu season is so grim - that while located in the Northern Hemisphere - Hong Kong is making arrangements to purchase a quantity of the recently revised Southern Hemisphere vaccine, as announced earlier this month in New flu vaccine ready by April.

As we’ve seen this year in North America, Hong Kong’s flu season has been dominated by a drifted H3N2 virus which has greatly reduced this year’s vaccine effectiveness, and its greatest impact has been on the elderly.

 

HK’s Dr. Ko Wing-man On Flu Reassortment Concerns

Reassortment is the mechanism where two different flu viruses infect the same cell simultaneously, and swap genetic material, producing a new, hybrid virus. -  Credit AFD

 

# 9686

 

At the same time that mainland China is experiencing their third winter wave of H7N9 infections, Hong Kong and the rest of southern China are embroiled in a particularly nasty H3N2 seasonal flu epidemic. 

 

Today’s flu update from Hong Kong’s CHP acknowledges:

 

Regarding severe cases, from noon yesterday (February 7) to noon today, four additional cases of influenza-associated admission to intensive care units or death (including two deaths) among adults aged 18 or above have been recorded under the enhanced surveillance in collaboration with public and private hospitals reactivated since January 2.

This brings the total number to 218 ( 142 deaths) so far. Among them, 207 were A(H3N2), five were B and six were A pending subtype. In the last winter season in early 2014, 266 (133 deaths) were filed.

Meanwhile, no additional cases of severe paediatric influenza-associated complication or death among children aged under 18 have been reported since yesterday via the ongoing reporting system. The total this year hence remains at 11 (no deaths) and all were A(H3N2). In 2014, 27 (four deaths) were filed.

 

Things are so bad - that while located in the Northern Hemisphere - Hong Kong is making arrangements to purchase a quantity of the recently revised Southern Hemisphere vaccine, as announced yesterday in New flu vaccine ready by April.

A couple of weeks ago, in Hong Kong CHP Update On Imported H7N9 Case, we looked at published reports saying that HK CHP director Dr. Ko Wing-man had publically expressed concerns over the possibility that this year’s seasonal flu, and the H7N9 virus, could cross paths and create a new, reassorted virus.

 

Today, based on reports in the South China Morning Post and Sputniknews, Dr. Ko Wing-man has apparently once again voiced those concerns.

 

Hong Kong Health Minister Warns of Possible New Deadly Virus Outbreak

© AFP 2015/ ISAAC LAWRENCE

 16:18 08.02.2015 (updated 16:54 08.02.2015)

Hong Kong's health minister stated that rampant seasonal flu in Hong Kong and the recent strain of bird flu detected in poultry could together give rise to a deadly new virus.

MOSCOW, (Sputnik) – The rampant seasonal flu in Hong Kong and the recent strain of bird flu detected in poultry could together give rise to a deadly new virus, Hong Kong's health minister said Sunday.

“If a person contracts two viruses, a gene recombination is likely to happen,” Ko Wing-man was quoted as saying by the South China Morning Post, adding that the mutation could lead to a more contagious virus.

(Continue . . . )

 

A novel/seasonal flu reassortment is not a new concern, nor is this scenario limited to H7N9, or the H3N2 virus. Anytime two different flu viruses inhabit the same host (human, avian, porcine, etc.) at the same time, the potential for seeing a reassortant virus exists. 

Most of the time, however, the resultant hybrid virus fails to thrive and spread, and it is never even noticed.

But when you have an abundance of seasonal flu co-circulating with a novel flu virus like H7N9, the odds of seeing a someone infected with both subtypes – admittedly a rare event – go up.  And the more opportunities these viruses have to get together, the better the chances are they will produce an offspring.

 

Last month, in EID Journal: Timing of Influenza A(H5N1) in Poultry and Humans Worldwide, 2004–2013, we looked exactly these concerns, albeit focusing on H5N1 and seasonal flu interactions.   The author’s wrote:

Abstract

Co-circulation of influenza A(H5N1) and seasonal influenza viruses among humans and animals could lead to co-infections, reassortment, and emergence of novel viruses with pandemic potential.

 

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.

 

And in 2010, 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.

While rarely detected, influenza A coinfections are probably more common than we realize.  Luckily, most do not result in the production of a hybrid strain, else we’d be hip deep in novel viruses all the time.

 

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

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

 

How big that risk really is, in terms of producing a pandemic virus, is unknown.  Most of these reassortant hybrids will fail and fade away unnoticed, either being biologically `flawed’ in some way, or simply not as competitive as existing strains.

 

The odds of any one viral assignation producing a viable, humanized virus is probably fairly remote.

The concern is, if these viruses get enough rolls of the genetic dice, they will eventually roll a natural.  Which is why we watch Hong Kong, mainland China, and Egypt so carefully this time of year.

A Dog & Cat Flu Review

 

# 9382

 

Until about a decade ago, it was widely (and erroneously) believed that dogs and cats were not generally susceptible to influenza A infections. 

 

That perception began to change in 2004 with two unrelated events; the jump of equine H3N8 influenza from horses to Florida greyhounds, and the infection by avian H5N1 of tigers fed infected chickens in Thailand.

 

While not considered major players (yet) in the spread of human or novel influenza viruses, their role as companion animals make dogs and cats of particular interest to influenza researchers.

 

First a look back at some of the evidence on dogs & cats susceptibility to influenza – then I’ll have a couple of new studies that shed additional light on their ability to contract, and spread, certain subtypes of flu.

 

In 2004, the H3N8 equine influenza – a strain that has been around in horses nearly a half century – was discovered to have jumped, and adapted to dogs, creating a new dog-specific (canine) lineage of H3N8. 

 

Since then, H3N8 has continued to spread among dogs both in North America and around the globe.

While we’ve yet to see any evidence that this equine/canine H3N8 virus can infect humans, there are a number of different H3N8 lineages out there, including the equine, canine, avian, and even a recently discovered Mammalian Adapted H3N8 In Seals.

And a related H3N8 virus is thought to have sparked the 1900 influenza pandemic, giving it a track record in humans, and is considered likely to return someday (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).

Added to this mix, in 2008 the CDC’s EID Journal carried the following report on a newly emerging canine flu in Korea.

 

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.

 

In late 2012, in China: Avian-Origin Canine H3N2 Prevalence In Farmed Dogs, we saw a study that found more than 12% of farmed dogs tested in Guangdong province carried a strain of canine H3N2 similar to that seen in Korea.

 

During the 2009 H1N1 pandemic we saw reports of dogs infected, and in the middle of the last decade we saw several reports indicating that dogs were susceptible to the H5N1 bird flu virus (see Study: Dogs And H5N1).

Cats, too, were infected during the 2009 H1N1 pandemic (see Companion Animals And Novel H1N1 & EID Journal: Pandemic H1N1 Infection In Cats), and In 2011, it was announced that Korea’s canine H3N2 had jumped to cats (see Korea: Interspecies Transmission of Canine H3N2).

 

Previously we’d seen reports of cats infected with the H5N1 virus after consuming infected birds.  The following comes from a World Health Organization GAR report from 2006.

H5N1 avian influenza in domestic cats

28 February 2006

(EXCERPTS)

Several published studies have demonstrated H5N1 infection in large cats kept in captivity. In December 2003, two tigers and two leopards, fed on fresh chicken carcasses, died unexpectedly at a zoo in Thailand. Subsequent investigation identified H5N1 in tissue samples.

In February 2004, the virus was detected in a clouded leopard that died at a zoo near Bangkok. A white tiger died from infection with the virus at the same zoo in March 2004.

In October 2004, captive tigers fed on fresh chicken carcasses began dying in large numbers at a zoo in Thailand. Altogether 147 tigers out of 441 died of infection or were euthanized. Subsequent investigation determined that at least some tiger-to-tiger transmission of the virus occurred.

In 2006, Dr. C.A. Nidom demonstrated that of 500 cats he tested in and around Jakarta, 20% had antibodies for the bird flu virus. In 2007 the FAO warned that: Avian influenza in cats should be closely monitored, and in 2012 the OIE reported on Cats Infected With H5N1 in Israel, although so far no sustained virus transmission in cats or from cats to humans has been observed.

 

Contrary to the prevailing scientific opinion until the early 2000’s, dogs and cats are obviously both susceptible to a variety of influenza A viruses. All of which proves that you never know what you are apt to find until you actually start looking for it. 

 

Which brings us to a pair of recently published studies.  The first being on the virulence (or lack, thereof) of H5N1 in dogs and cats, and what that might portend as far as transmission is concerned.

 

Arch Virol. 2014 Nov 22. 

Greater virulence of highly pathogenic H5N1 influenza virus in cats than in dogs.

Kim HM¹, Park EH, Yum J, Kim HS, Seo SH.

Author information

Abstract

Highly pathogenic H5N1 influenza virus continues to infect animals and humans. We compared the infectivity and pathogenesis of H5N1 virus in domestic cats and dogs to find out which animal is more susceptible to H5N1 influenza virus. When cats and dogs were infected with the H5N1 virus, cats suffered from severe outcomes including death, whereas dogs did not show any mortality.

Viruses were shed in the nose and rectum of cats and in the nose of dogs. Viruses were detected in brain, lung, kidney, intestine, liver, and serum in the infected cats, but only in the lung in the infected dogs. Genes encoding inflammatory cytokines and chemokines, Toll-like receptors, and apoptotic factors were more highly expressed in the lungs of cats than in those of dogs.

Our results suggest that the intensive monitoring of dogs is necessary to prevent human infection by H5N1 influenza virus, since infected dogs may not show clear clinical signs, in contrast to infected cats.

An interesting result, considering that last spring  Korea Detected H5N8 Antibodies In asymptomatic Farm Dogs.

The second study, which appears in the December issue of the EID Journal, looks at the ability of cats to contract, and spread a contemporary strain of the equine/canine H3N8 virus.

 

Equine Influenza A(H3N8) Virus Infection in Cats

Shuo Su¹, Lifang Wang¹, Xinliang Fu, Shuyi He, Malin Hong, Pei Zhou, Alexander Lai , Gregory Gray, and Shoujun Li

Abstract

Interspecies transmission of equine influenza A(H3N8) virus has resulted in establishment of a canine influenza virus. To determine if something similar could happen with cats, we experimentally infected 14 cats with the equine influenza A(H3N8) virus. All showed clinical signs, shed virus, and transmitted the virus to a contact cohort.

Conclusions

That cats are susceptible to EIV by direct inoculation is not surprising because infection of cats with various influenza A viruses has been reported. Feline respiratory tract epithelial cells contain sialic acid α-2,3-galactose β-1,3-N-acetyl galactosamine (SA α2,3 gal) receptors for avian and equine influenza viruses and SA α2,6 gal receptors for mammalian influenza virus (13).

However, our finding of horizontal transmission of EIV among cats is significant. If transmission occurs outside the laboratory, and if the basic reproduction rate is higher than 1.0, then EIV could potentially establish itself and circulate in this new host species. Why it has not yet happened naturally, as it did for canine influenza virus (H3N8), remains to be determined. Possibilities include lower transmission efficiency, lower probability of horse–cat contact, less virus shedding in a laboratory, or feline behavior (less social contact than dogs).

 

These researchers repeated this experiment with an older strain of the equine H3N8 virus, and while some of the cats seroconverted, they all remained asymptomatic. Illustrating the variance of virulence one often finds between clades or strains of the same influenza A subtype.

.

In just over a decade we’ve gone from believing that dogs and cats aren’t really susceptible to flu to viewing them as Potential `Mixing Vessels’ For Influenza. 

 

Last summer, in Canine H3N2 Reassortant With pH1N1 Matrix Gene, we looked at this precise scenario. At roughly the same time the American Society for Microbiology issued this warning:

 

Evolution of Equine Influenza Led to Canine Offshoot Which Could Mix With Human Influenza

WASHINGTON, DC – June 19, 2014 – Equine influenza viruses from the early 2000s can easily infect the respiratory tracts of dogs, while those from the 1960s are only barely able to, according to research published ahead of print in the Journal of Virology. The research also suggests that canine and human influenza viruses can mix, and generate new influenza viruses.

(Continue . . . )

 

Although  it’s true that pigs and birds are considered  far superior biological `flu factories’,  any jump of a novel flu virus to a new species is viewed with concern, because it affords the virus new opportunities to acquire host adaptations – or reassort with other viruses – and thereby increases its chances of becoming a human health threat.

While the future role of dogs and cats in the evolution of influenza is subject to debate, for now, your pet is at far greater risk of catching the flu from you, than you are from it (see Companion Animals & Reverse Zoonosis).

I Got It From Carol

 

 

# 8980

My annual flu shot, that is.      

 

One of the reasons I’m a little late posting this morning is that I had some errands to run, and on the way popped into my local pharmacy to get the flu  vaccine.  Carol is my friendly local CVS pharmacist, and she gives a damn fine shot.

 

I know what you are thinking: It’s only August . . .flu season is still a couple of months away . . . .

 

True, but flu viruses circulate year-round, not just during `flu season’ and flu cases can start to ramp up as early as September.  Since it takes a couple of weeks for flu shot to reach maximum effectiveness, I always try to get the flu shot earlier rather than later.  

 

Here was what the CDC has to say about the timing of getting flu shots.

 

Should I wait to get vaccinated so that my immunity lasts through the end of the season?

CDC and the Advisory Committee on Immunization Practices (ACIP) recommend that flu vaccinations begin soon after vaccine becomes available, ideally by October. However, as long as flu viruses are circulating, it is not too late to get vaccinated, even in January or later. While seasonal flu outbreaks can occur as early as October, flu activity most often peaks in January or later. Since it takes about two weeks after vaccination for antibodies to develop in the body that protect against flu virus infection, it is best that people get vaccinated in time to be protected before flu viruses begin spreading in their community. Although immunity obtained from flu vaccination can vary by person, previously published studies suggest that immunity lasts through a full flu season for most people.

There is some evidence, however, that immunity may decline more quickly in older people. For older adults, another flu vaccine option is available called the “high-dose” vaccine, which is designed specifically for people 65 and older. This vaccine contains a higher dose of antigen (the part of the vaccine that prompts the body to make antibody), which is intended to create a stronger immune response in this age group. For more information, see Fluzone High-Dose Seasonal Influenza Vaccine Questions and Answers.

 

I also get the flu vaccine early each year, because if I’m going to promote the practice, I’d darn well better be willing to be first in line to get the shot.  Here are the CDC’s recommendations for who should get the shot each year.

Everyone who is at least 6 months of age should get a flu vaccine this season. This recommendation has been in place since February 24, 2010 when CDC’s Advisory Committee on Immunization Practices (ACIP) voted for “universal” flu vaccination in the United States to expand protection against the flu to more people.

While everyone should get a flu vaccine this season, it’s especially important for some people to get vaccinated.

Those people include the following:

• People who are at high risk of developing serious complications (like pneumonia) if they get sick with the flu.
  • People who have certain medical conditions including asthma, diabetes, and chronic lung disease.
  • Pregnant women.
  • People younger than 5 years (and especially those younger than 2), and people 65 years and older.
  • A complete list is available at People Who Are at High Risk of Developing Flu-Related Complications.
• People who live with or care for others who are at high risk of developing serious complications (see list above).
  • Household contacts and caregivers of people with certain medical conditions including asthma, diabetes, and chronic lung disease.
  • Household contacts and caregivers of infants younger than 6 months old.
  • Health care personnel.

More information is available at Who Should Get Vaccinated Against Influenza.

 

Even though I get the jab every year, I do recognize its limitations.

 

As we’ve discussed before, flu vaccines – while considered very safe – most years only offer a moderate level of protection against influenza, that their VE (vaccine effectiveness) can vary widely between flu shot recipients, and is often substantially reduced among those older than 65 or with immune problems.

 

As an example, in October of 2011, in CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis, we saw a major review indicating the TIV (Trivalent Influenza Vaccine) - during 8 of 12 flu seasons (67%) – produced a combined efficacy of only 59% among healthy adults (aged 18–65 years).

 

They found the protective effects of the flu vaccine could vary considerably from one season to the next, as well as among different age groups (see Study: Flu Vaccines And The Elderly).

 

Still, given their safety record, and relative low cost, I consider them to be good insurance against what can sometimes be a serious illness – particularly as I’m getting older.  As an added incentive, we recently saw a study - that while far from conclusive - suggesting that the Flu Vaccine May Reduce Heart Attack Risk.

 

There is no doubt that we need better flu vaccines – particularly for those at greatest risk from influenza infection; the elderly and those with chronic illnesses (see CIDRAP: The Need For `Game Changing’ Flu Vaccines). But until they can be developed, the vaccines we have can and do help reduce the spread of the virus.

 

While you might not have thought about it, getting your seasonal flu shot each year should be part of your overall preparedness plan. During a disaster or prolonged emergency you are likely to be tired, stressed, and your immune systems could be weakened.

 

The last thing you need during a crisis is to be sick with the flu on top of it.

 

All things considered, getting a flu shot every year makes a lot of sense.  For more, you may wish to revisit:

 

CDC: Flu Shots Reduce Hospitalizations In The Elderly

Research: Low Vaccination Rates Among 2013-2014 ICU Flu Admissions

Two Studies On The 2009 Pandemic Flu Vaccine & Pregnancy

Retraction Of Major Narcolepsy – Autoimmune Link Paper

Photo Credit CDC – Sleep and Sleep Disorders

 

# 8897

 

In August of 2010, roughly 9 months after the first vaccines for the pandemic H1N1 virus became available, we began to see reports of an increase in narcolepsy among children and adolescents in Northern Europe who had received a specific formulation of the vaccine; GSK’s Pandemrix ® (see Finland Suspends Use of Pandemrix Vaccine). 

 

In February of 2011, the Finnish National Institute for Health and Welfare released an interim report on what they  called  `a probable link’ between GSK’s Pandemrix vaccination, and an increase in narcolepsy in children and adolescents 4-19 years of age.  Two findings of note were:

 

• While the Pandemrix vaccine was taken by 31 million people across 47 countries, other than Finland, Sweden and Iceland, no other countries reported an increase in narcolepsy in 2010. 
• Iceland, unlike Finland, reported an increase in narcolepsy among unvaccinated children during this same time period.

 

As it turns out, Iceland wasn’t alone in seeing a spike in narcolepsy after the first pandemic wave, as a Stanford study appeared in August of 2011 in the Annals of Neurology called  "Narcolepsy Onset is Seasonal and Increased Following the H1N1 Pandemic in China", among a population who never received the flu vaccine.

 

While the cause of narcolepsy remains a mystery, it has long been  assumed to be an auto-immune disease, and so seeing spikes following a novel flu pandemic – or even  vaccination – made sense. Narcolepsy is probably more common than most people realize, with its prevalence estimated at being between 25 and 50 per 100,000 people.

The narcolepsy-Pandemrix link story continued with a series of studies and reports that found a link between the two, but not a cause.  While still a mystery, the point became somewhat moot, since Pandemrix was no longer in use.

 

That is, until December of 2013 when Immunologist Elizabeth Mellins and narcolepsy researcher Emmanuel Mignot at Stanford University School of Medicine published a paper in Science Translational Medicine  (Link) that was hailed as major breakthrough (see Ed Yong’s report in  Nature Narcolepsy confirmed as autoimmune disease) in understanding the disease.

Although I’m badly over-simplifying a complex paper, the authors found that a protein found in the brain – hypocretin – which helps keep us alert and awake, was similar enough to a protein in the H1N1 virus that the body’s immune system could occasionally mistake it for the virus and send T cells to destroy hypocretin-secreting-neurons, thus inducing narcolepsy.

 

This concept, known as “molecular mimicry”, was an elegant explanation, and was widely reported in the academic and mainstream press.  It also suggested that other infections could trigger similar reactions. 

That is, until yesterday when the paper was retracted by the authors.

This from  Stanford Medical News.

 

Stanford researchers retract study examining link between narcolepsy, H1N1

Stanford researchers have retracted a 2013 study that described a possible immunological connection between narcolepsy and the H1N1 influenza virus.

Jul 30 2014

A paper published Dec. 18, 2013, in Science Translational Medicine that described a possible immunological connection between narcolepsy and the H1N1 influenza virus is being retracted at the request of the authors at the Stanford University School of Medicine.

Sleep researcher Emmanuel Mignot, MD, PhD, a professor of psychiatry and behavioral sciences, and his co-authors requested the retraction because they were unable to replicate some of the results reported in the paper.

The journal published the retraction notice online today.

 

While this retraction doesn’t invalidate the theory that `molecular mimicry’ plays a role in the development of narcolepsy, it is now far from `confirmed’ as earlier reports indicated.

 

In a perfect world, the conclusions drawn from scientific research would always be unequivocal and we would be able to automatically accept their results as being the final word on any  subject.  But no research methodology is perfect, all studies are subject to limitations, and it isn’t unusual to end up with conflicting results from different research teams.

 

Science is often messy and there are few `Eureka!’ moments of sudden clarity. We usually get to the truth by fits and starts – and that can often take years or even decades to sort out.  

 

For some earlier blogs on the vagaries of research results, you may wish to revisit:

 

When Studies Collide 

When Studies Collide (Revisited)

MOSAIC: Video `How To Catch The Flu’

 

Credit – How To Catch Flu – Imperial College

 

 

# 8865

 

MOSAIC (Mechanisms of Severe Acute Influenza Consortium) was set up in the summer of 2009 at Imperial College in the UK during the H1N1 pandemic to investigate `the clinical, viral, host genetic, immunological and molecular events underlying severe influenza infection’.

Sponsored by the Wellcome Trust and the Medical Research Council (MRC), UK – MOSAIC’s network of 45 researchers and their teams have advanced our knowledge of influenza, including learning about the role that the IFITM3 gene plays in the hosts vulnerability to influenza (see Luck Of The Draw).

 

Getting people to understand that influenza is neither trivial, or predictable has been a major frustration for public health officials for decades.  It is a message we saw resonate briefly during the opening days of the 2009 pandemic, but as it became apparent the H1N1 virus wasn’t extraordinarily deadly, the public quickly lost interest.

In an attempt to help raise public awareness on the dangers of influenza – and its ability to mutate into new and potentially deadly strains - MOSAIC researchers have collaborated with collaborated with illustrator Steven Appleby and animator Pete Bishop to make a short (and entertaining) animated film called 'How to Catch Flu'.

What better way to end the week than to spend a few quality minutes with a sage, anthropomorphized flu virus?

 

For more on this film, and MOSAIC,  Imperial College, London published a background article today under News & Events.  Follow the link below to read:

 

Flu tells its story in new film

by Francesca Davenport 25 July 2014

Influenza researchers have collaborated with an illustrator to make a short animated film titled 'How to Catch Flu'.

The film is presented by a flu virus who gives a comical and slightly macabre account of flu’s history and its possible future. Sitting in an armchair, it informs viewers of its evolution over the years, its preferred victims and what can facilitate or stop its spread. The film then provides advice on how to avoid the flu and limit its impact.

(Continue . . .)

PNAS: Testing An IL-15 Adjuvanted Vaccinia-Based `Universal’ Flu Vaccine (In Mice)

 

 

# 8422

 

The headlines this afternoon – particularly those coming out of Hong Kong – are proclaiming a `Breakthrough’  that may eventually  lead to a universal flu vaccine.  The key word is `eventually’, as so far this breakthrough has only been tested in mice . . . and as we’ve seen before in medical research, mice are sometimes terrible liars.

 

The excitement is over a study, published yesterday in PNAS,  where researchers from the University of Hong Kong, described how they piggy-backed a broadly protective flu vaccine onto a live vaccinia virus, and in it, incorporated a human cytokine (interleukin-15) adjuvant.

 

First a link to the study, then some excerpts from the HKU press release, after which I’ll be back with a bit more. (NOTE: If all of this sound vaguely familiar, there is a good reason for that, which I’ll go into also).

 

IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection

Sophie A. Valkenburg, Olive T. W. Li, Polly W. Y. Mak, Chris K. P. Mok, John M. Nicholls, Yi Guan, Thomas A. Waldmann, J. S. Malik Peiris, Liyanage P. Perera, and Leo L. M. Poon

 

Significance

We present a novel vaccine that elicits protective immune responses against many different influenza viruses belonging to both group 1 and 2 lineages. The vaccine uses a live vaccinia virus that expresses multiple H5N1 influenza viral proteins and the cytokine IL-15 to stimulate the immune system. The vaccine was able to induce T-cell immune responses that recognize different influenza viruses and these immune responses were augmented when exposed to a challenge virus, resulting in protection against a lethal disease. Vaccine-induced CD4⁺ T cells that coordinate immune responses were found to be more important than CD8⁺ T cells in conferring protection. Our vaccine provides a promising strategy for universal protection against novel and emerging influenza viruses.

(Continue . . . )

While not used much today, the vaccinia virus is the mild `pox’ virus that was used to eradicate smallpox back in the 1970s.  It has been investigated as potential `carrier’ for recombinant vaccines for at least 20 years, partially because it is relatively easy to quickly manufacture, and because -  with `billions already served’ - it has an enviable safety record.

 

While fairly benign for those with good immune systems, the standard vaccinia virus could pose a risk to those with immunocompromised systems, so a highly attenuated  Modified vaccinia Ankara (also known as MVA), might be substituted to reduce the risk.

 

Unlike conventional flu vaccines, which sometimes require traditional adjuvants (like squalene, oil & water, and other proprietary formulas) to increase the immune response (particularly for hard to defend against avian H5 & H7 strains), this experimental vaccine uses a gene for interleukin-15 (IL-15) to stimulate the immune system.

 

This paper has an impressive pedigree, including such familiar names as Dr. Leo Poon, Malik Peiris, and Yi Guan. Details are provided via the following press release:

 

April 1, 2014

HKU develops a universal influenza A vaccine that can elicit protective immune responses against viruses of multiple HA subtypes

A research team, led by Dr Leo Poon, Associate Professor of the School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), in collaboration with the National Cancer Institute, National Institutes of Health, United States of America (USA), has developed a novel influenza A vaccine that can induce protective responses against distinctly different influenza A viruses in mice, including the avian H7N9 virus. The study has been published this morning (April 1, 2014) in an international scientific journal, Proceedings of the National Academy of Sciences of the United States of America.

Research Implications
The research team has developed a novel vaccine against influenza A viruses. In the vaccine, a live recombinant vaccinia virus (Wyeth/IL-15/5Flu) that expresses multiple H5N1 influenza viral proteins and the cytokine IL-15 is used to stimulate robust immune responses. The vaccinia virus is useful as it is also used as a vaccine for smallpox, and is therefore already licensed for human use with over a billion doses given so far. The vaccine can be adapted for mass production in case of a worldwide influenza outbreak.

The novel influenza A vaccine is able to induce T-cell immune responses against influenza A viruses of different hemagglutinin (HA) subtypes, overcoming the limitations of the current seasonal vaccines. These immune responses can provide protection against lethal challenge of influenza A viruses by reducing the amount of viruses and the duration of illness. In addition, vaccine-induced CD4+T cells that coordinate immune responses are found to be more important than CD8+T cells in inducing protection. These results reveal an important yet underappreciated role of CD4+T cells in initiating cross-reactive protection against influenza A viruses. Overall, this vaccine provides a promising strategy for universal protection against new and emerging influenza viruses.

(Continue . . . )

Essentially, in hundreds of lab tests, and challenged by a number of virulent flu strains, this vaccine provided between 80% and %100% protection . . . in mice.

 

While a promising strategy for someday producing a `universal’ flu vaccine, lead researcher, Dr Leo Poon Lit-man, told the South China Morning Post today, “ . . . it might take years before the vaccine is tested in human clinical trials.”

 

If all of this sounds familiar, it is because many of these same researchers published a similar study back in 2009 in the Journal of Immunology.

 

Vaccinia Virus-Based Multivalent H5N1 Avian Influenza Vaccines Adjuvanted with IL-15 Confer Sterile Cross-Clade Protection in Mice

Leo L. M. Poon, Y. H. Connie Leung, John M. Nicholls, Pin-Yu Perera, Jack H. Lichy, Masafumi Yamamoto, Thomas A. Waldmann, J. S. Malik Peiris,and Liyanage P. Perera

 

Today’s study builds on this previous research, which was pretty much H5N1-centric.  The author’s explain in today’s press release:

 

In this study, the use of this unique vaccine was extended to mediate heterosubtypic immunity towards viruses of different subtypes. The vaccine protected mice against the fatal attacks by the most recent human H7N9, seasonal H3N2, pandemic H1N1/2009, and highly pathogenic H7N7 influenza A viruses

 

Of course, the standard caveats apply:

 

• What works well in mice doesn’t always always work well in humans.
• There are a good many unknowns when it comes to boosting the human immune system, even when using a `human cytokine’ gene, so much more study is required.
• Most of those alive before 1970 were vaccinated with the vaccinia (smallpox) vaccine, and it isn’t really known how much that will affect this vaccine’s ability to deliver its recombinant payload. 

 

It has literally been 5 years since the first study was published, and it may well be another five years before human clinical trials can be conducted on this novel vaccine technique. 

 

While it is unknown whether we have five years before the next pandemic, in complex research projects such as this one, sometimes there are no alternatives but to take the long view.

Spot Shortages Of Tamiflu Reported In Some Regions

Photo Credit – Wikipedia

 

# 8109

 

With the 2013-14 influenza season now well underway, and concerns over the severity of the H1N1 virus – particularly in younger patients and those with co-morbidities – the CDC is urging doctors to consider the early use of antivirals in high risk patients with suspected or confirmed influenza (see CDC HAN Advisory On Early pH1N1 Influenza Activity).

 

While there does not seem to be a national shortage of oseltamivir (Tamiflu ®) – the most commonly prescribed antiviral for influenza – in a few regions (mainly in the South) that have already been hit hard by the flu, some pharmacies are reporting trouble keeping the drug in stock.

 

A couple of  reports on these shortages, after which I’ll be back with a little more on Tamiflu, and this year’s H1N1 flu.

 

Shortage in flu medication worries pharmacists

LITTLE ROCK, Ark. (KTHV) - "We can't find the regular adult dose anywhere right now," Dr. Ray Turnage explained.

Turnage is one of many pharmacists dealing with a shortage of Tamiflu. He said, "There's only one manufacturer for that drug and nationwide all the wholesalers are saying it's a manufacture delay."

Tamiflu is the only medication on the market used to treat the flu and with a shortage in the drug, it could create problems for patients needing it. "Probably the demand is exceeding their supply. So that's the problem is we can't even get adult doses right now," Turnage continued.

Although there have been very minimal cases of the flu this year in Little Rock, with 3 to 4 months left in the flu season, that could change pretty quickly. If it does, Tamiflu in stock could disappear. Turnage said, "That's part of the situation is a few families can, if they can find it, can take all that the pharmacy may have."

(Continue . . .)

 

Shortage reports on Tamiflu in Atlanta, local pharmacies stocked – WSOC-TV

 

The bottom line is, that if you are prescribed Tamiflu, you may have to call around to more than one pharmacy to locate the drug.

While Tamiflu continues to get a strong recommendation from the CDC (see CDC Research On Benefits Of Antivirals For Uncomplicated Influenza), you’ll find no shortage of critics of the drug.  Due in large part to a prolonged reluctance on the part of Roche laboratories to release all of their clinical trial data, and a not totally undeserved reputation of `Big Pharma’ to massage test results. 

 

This has resulted in a vociferous backlash against the government stockpiling of Tamiflu in some quarters (see Dr. Ben Goldacre Opinion Piece). 

 

While academics and activists tend to have a dim view of Roche and their antiviral drug, clinicians obviously see value in oseltamivir,  and continue to prescribe it.  The CDC continues to recommend its use – particularly for high-risk influenza patients - or for the treatment of novel flu (see 2012 blog The CDC Responds To The Cochrane Group’s Tamiflu Study).

 

Although this year’s flu season is being billed in the media as `The Return of Swine Flu’, in truth, the H1N1 virus never departed.  But it has been dominated in North America by the H3N2 virus for the past couple of years.   The following snapshot of last year’s moderately severe flu season comes from last summer’s  MMWR Influenza Activity — United States, 2012–13 Season and Composition of the 2013–14 Influenza Vaccine.

 

Among the seasonal influenza A viruses, 34,922 (68%) were subtyped; 33,423 (96%) were influenza A (H3N2) viruses, and 1,497 (4%) were pH1N1 viruses. In addition, two variant influenza A (H3N2v) viruses were identified.

 

The season before that (2011-12) was the mildest flu season in decades (see 2011-2012 Flu Season Draws to a Close), that while H3N2 dominated, neither strain had a huge impact.

 

The truth is, flu seasons can vary greatly in impact from year-to-year,and with two influenza A strains in global circulation, we usually see one strain or the other dominate (although what strain is dominant in North America my differ from what is dominant in Europe, or Asia the same year).  Often we see 2 or 3 years with one strain in control, and then – as community immunity levels wane – the other takes hold.

 

The CDC’s most recent attempt to estimate the number of deaths associated with flu in the United States finds:

 

An August 27, 2010 MMWR report entitled “Thompson MG et al. Updated Estimates of Mortality Associated with Seasonal Influenza through the 2006-2007 Influenza Season. MMWR 2010; 59(33): 1057-1062.," provides updated estimates of the range of flu-associated deaths that occurred in the United States during the three decades prior to 2007. CDC estimates that from the 1976-1977 season to the 2006-2007 flu season, flu-associated deaths ranged from a low of about 3,000 to a high of about 49,000 people.

 

As much as a 16-fold difference in the number of estimated deaths between a mild flu season, and a heavy one. 

 

Thus far, its been H1N1’s year to roar, and since that strain often impacts those under the age of 65, it tends to get more publicity. The flu death of a young adult from influenza is more unexpected, and has more societal impact, than that of an octagenarian.  And this year, sadly, we are seeing a fair number of such reports (see Texas DSHS Statement On Recent Spike In Flu Activity).

 

Regardless of the strain of flu in circulation, you are much better off avoiding infection rather than treating it. So while it may only provide moderate protection, getting the flu shot each year is cheap insurance. 

That, and following good flu hygiene practices (covering coughs, washing hands frequently, staying home when sick, avoiding close contact with those who are sick),  are your best defense against our yearly flu epidemic.

ECDC Technical Report: Barriers & Drivers For Seasonal Influenza Vaccination

 

 

# 7932

 

Despite their limitations (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis) most public health officials view getting the seasonal flu vaccine each year as the single best preventative against catching influenza.  Flu vaccines have an enviable safety record, and most years provide a moderate level of protection against the strains in circulation.

 

Unfortunately, the uptake of flu vaccines  – including among those at higher risk of influenza complications and and healthcare workers – remains far lower than most public health authorities would like to see.

 

Today the ECDC has published a technical report that reviews the existing literature on the drivers, and barriers, to seasonal influenza vaccination.  The full report runs about 33 pages, and will be of most interest to those involved in flu vaccine deployment, and public health messaging.

 

Note: I encountered an error when trying to open this PDF file with some software (which will hopefully be corrected)  – so check back if you have a problem.

Below you’ll find the press release, summary, and link.

 

 

Evidence review on the barriers and drivers of seasonal influenza vaccination coverage in Europe

04 Nov 2013

​The new ECDC report aims to provide a critical review of evidence on the barriers and drivers of seasonal influenza vaccination coverage in the EU/EEA. The report focuses on high-risk groups where high coverage of seasonal flu vaccination is most important. The quality and breadth of evidence on interventions varies considerably for the different groups:

• For the elderly population (65 year olds and older) and healthcare workers, there is published evidence on specific types of interventions to increase the uptake of seasonal flu vaccination.
• For patients with chronic conditions, the evidence is scattered and not concentrated on any particular groups of chronically ill people, limiting the transferability of conclusions and application to this group as a whole.
• For pregnant women and children, the evidence found was scarce and low permitting few conclusions.

The report tries to address the following key questions:

• What are the current gaps in research on the drivers and barriers to increase seasonal flu vaccination coverage?
• Can we identify examples of good practice that increase vaccination uptake in all groups?
• How can the current low rates of healthcare workers’ influenza vaccination coverage be improved?

Every winter, influenza epidemics cause significant morbidity and mortality throughout Europe. High-risk groups such as older people, individuals with chronic diseases, pregnant women and small children are most affected by these epidemics. Healthcare workers are also at high risk of getting influenza or transmitting it to patients. Seasonal vaccination against flu viruses reduces the burden of disease in these groups and is widely available in most EU/EEA countries.

The 2009 Council of the European Union Recommendation on seasonal influenza vaccination encourages countries to implement measures that would increase seasonal influenza vaccination uptake to at least 75% for defined older age groups, and, if possible, for other risk groups. In support of this, the new ECDC report summarises the evidence on what are the barriers and what are the drivers for seasonal influenza vaccination by each risk group.

 

 

Some recent seasonal influenza vaccine related blogs include:

 

JAMA: Flu Vaccine and Cardiovascular Outcomes

PLoS One: Limited Effectiveness Of Flu Vaccines In The Elderly

BMC Infectious Diseases: Waning Flu Vaccine Protection In the Elderly

NPM13: Giving Preparedness A Shot In The Arm

JAMA: Flu Vaccine and Cardiovascular Outcomes

 

# 7890

 

One of the problems with determining the true burden of influenza on the public’s health is that influenza is rarely listed as the primary cause of death when a patient dies with a history of other co-morbidities like coronary artery disease, Asthma, Diabetes, or COPD.   Yet we know that during the winter months, when influenza and other respiratory viruses are at their height – overall mortality goes up. 

 

Roughly 15 years ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer. While cold weather combined with strenuous physical activity (like clearing snow from sidewalks) have often been blamed for this spike, even in balmy Southern California, studies have shown a 33% increase in heart attacks over the holidays (cite).

 

Although not the first to do so, a year ago  in Study: Influenza And Heart Attacks, we looked at research that appeared in the Journal of Infectious Diseases that suggested Influenza - and other acute respiratory infections - can act as a trigger for heart attacks.  

Despite often disappointing vaccine effectiveness (VE) numbers for those over the age of 65 (see NFID: The Challenges Of Influenza In Older Adults), in recent years we’ve seen a series of studies that have suggested that the flu vaccine may be partially protective against heart attacks. 

 

In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%. Almost immediately questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned). The primary concern was these researchers only looked at heart attacks during `flu season’, without the control of looking at AMI risks year-round.

 

Just last August (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at a new study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks.

 

Today, another study, which appears in JAMA, that performed a meta-analysis of  5 published and 1 unpublished randomized clinical trials involving  6735 patients - some of whom received a flu shot while others received a placebo - and calculated the number of cardiac events each group suffered in the months that followed. 

 

Among those who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months.

 

First a link to the JAMA study, and then some excerpts from the press release from  Women's College Hospital at the University of Toronto:

 

Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients

A Meta-analysis

FREE

Jacob A. Udell, MD, MPH, FRCPC¹; Rami Zawi, MD²; Deepak L. Bhatt, MD, MPH^3,4; Maryam Keshtkar-Jahromi, MD, MPH^5,6; Fiona Gaughran, MD^7,8; Arintaya Phrommintikul, MD⁹; Andrzej Ciszewski, MD¹⁰; Hossein Vakili, MD¹¹; Elaine B. Hoffman, PhD⁴; Michael E. Farkouh, MD, MSc, FRCPC¹²; Christopher P. Cannon, MD⁴

Results Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.

Conclusions and Relevance In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.

 

 

From the press release:

Flu shot halves risk of heart attack or stroke in people with history of heart attack, study finds

TORONTO, ON, October 22, 2013 — The flu vaccine may not only ward off serious complications from influenza, it may also reduce the risk of heart attack or stroke by more than 50 per cent among those who have had a heart attack, according to new research led by Dr. Jacob Udell, a cardiologist at Women's College Hospital and clinician-scientist at the University of Toronto. What's more, the vaccine's heart protective effects may be even greater among those who receive a more potent vaccine.

"Our study provides solid evidence that the flu shot helps prevent heart disease in vulnerable patients —with the best protection in the highest risk patients," Dr. Udell said. "These findings are extraordinary given the potential for this vaccine to serve as yearly preventative therapy for patients with heart disease, the leading cause of death among men and women in North America."

Published today in the Journal of the American Medical Association, the study reviewed six clinical trials on heart health in people who received the flu vaccine. The studies included more than 6,700 patients with a history of heart disease. The researchers found people who received the flu shot:

• Had a 36 percent lower risk of a major cardiac event (heart attack, stroke, heart failure, or death from cardiac–related causes) one year later
• Had a 55 percent lower risk of a major cardiac event if they had a recent heart attack
• Were less likely to die from cardiac-related and other causes, and
• Were less likely to have a major cardiac event with a more potent vaccine compared with the standard seasonal vaccine

(Continue . . .)

 

While not a slam dunk (larger, more robust more studies are needed), this latest report adds to the body of evidence suggesting that influenza contributes significantly to cardiovascular events, and that flu vaccines may be useful in reducing cardiac mortality rates. 

I’m fully cognizant of the limitations of today’s flu vaccines, and try not to `oversell’  them in this blog. Nevertheless, I get one every year and urge that others do the same.

 

Not because they are 100% protective.  They aren’t. But they do offer moderate levels of protection (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis), and have an excellent safety profile. 

 

We take sensible precautions every day – like buckling up when we drive, or wearing a helmet when we bike. None of these provide a 100% guarantee of avoiding injury, but they make sense because they increase our odds of walking away from an accident.   

 

I view getting a yearly flu shot in much the same way.