CDC Study: Lives Saved By the Flu Vaccine

 

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Given this year’s poor performance, and resultant bad press, from the seasonal flu shot it is understandable that the CDC, and other public health entities, would want to `rehabilitate’ the flu vaccine’s recently maligned reputation.  Particularly since - even in a `bad-match’ year - the flu vaccine can save lives.

 

The flu shot – while far from perfect – has an excellent safety profile, and most years provides a moderate degree of protection against seasonal influenza.  

 

As regular readers of this blog already know, I get one every year. And while I sometimes worry that the benefits (and effectiveness) of the flu vaccine are oversold, flu vaccines remain our best protection against a virus that is estimated to kill a half million people around the globe each year.    

 

I often liken it to wearing a seatbelt – something that cannot guarantee you’ll walk away from a head-on collision - but it does definitely improve your chances.

 

Flu shots do not, however, protect against non-influenza respiratory viruses. And this year – due to the late arrival of a `drifted’ H3N2 virus (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus) – it didn’t do very well against influenza either.

 

Seasonal flu VE (Vaccine Effectiveness) ratings, which normally run 50%-60%, came in at a disappointing 18% according to the CDC’s Updated Estimated Seasonal Flu Vaccine Effectiveness report.

Given the speed by which influenza viruses mutate, and the need for six months lead time to create, produce, and deploy the vaccine, it is inevitable that some years the vaccine will miss its mark. 

 

Our reliance on what is essentially 50 year-old vaccine production technology is a bottleneck we’ve discussed often (see Revisiting CIDRAP’s - The Need For Better Flu Vaccines), and one that could really come to haunt us should a pandemic virus emerge. 

 

Showing that even a modestly effective vaccine can save lives, we have the following CDC sponsored study published in the journal Vaccine, followed by a press statement from the CDC.

 

Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14

Ivo M. Foppa^{a, b, , ,} , Po-Yung Cheng^{a, b}, Sue B. Reynolds^{a, c}, David K. Shay^a, Cristina Carias^{d, e}, Joseph S. Bresee^a, Inkyu K. Kim^{a, b}, Manoj Gambhir^d, Alicia M. Fry^a

Abstract

Background

Excess mortality due to seasonal influenza is substantial, yet quantitative estimates of the benefit of annual vaccination programs on influenza-associated mortality are lacking.

Methods

We estimated the numbers of deaths averted by vaccination in four age groups (0.5 to 4, 5 to 19, 20 to 64 and ≥65 yrs.) for the nine influenza seasons from 2005/6 through 2013/14. These estimates were obtained using a Monte Carlo approach applied to weekly U.S. age group-specific estimates of influenza-associated excess mortality, monthly vaccination coverage estimates and summary seasonal influenza vaccine effectiveness estimates to obtain estimates of the number of deaths averted by vaccination. The estimates are conservative as they do not include indirect vaccination effects.

Results

From August, 2005 through June, 2014, we estimated that 40,127 (95% confidence interval [CI] 25,694 to 59,210) deaths were averted by influenza vaccination. We found that of all studied seasons the most deaths were averted by influenza vaccination during the 2012/13 season (9398; 95% CI 2,386 to 19,897) and the fewest during the 2009/10 pandemic (222; 95% CI 79 to 347). Of all influenza-associated deaths averted, 88.9% (95% CI 83 to 92.5%) were in people ≥65 yrs. old.

Conclusions

The estimated number of deaths averted by the US annual influenza vaccination program is considerable, especially among elderly adults and even when vaccine effectiveness is modest, such as in the 2012/13 season. As indirect effects (“herd immunity”) of vaccination are ignored, these estimates represent lower bound estimates and are thus conservative given valid excess mortality estimates

 

 

CDC Study: Flu Vaccine Saved 40,000 Lives During 9 Year Period

March 30, 2015 – The seasonal flu vaccine prevented more than 40,000 flu-associated deaths in the United States during a nine year period from 2005-2006 through 2013-2014 according to estimates in a new study published in the journal Vaccine. This estimate represents a little less than a one-quarter (22%) reduction in the deaths that would have occurred in the absence of flu vaccination during that time. CDC has estimated previously that seasonal flu-associated deaths in the United States range between 3,000 and 49,000 people each year.

Estimates from the study showed that the majority of the flu-associated deaths prevented—nearly 89 percent (88.9%)—were in people 65 years of age and older. Next to older people, young children 6 months through 4 years of age benefitted most from flu vaccine in terms of the percentage of deaths averted. Children younger than 5 years old and adults 65 years of age and older are at high risk of serious flu complications and typically account for the majority of flu-associated deaths and have the highest flu-associated hospitalization rates.

The study included a breakdown of deaths prevented by season. The most deaths were prevented during the 2012-2013 season, when nearly 9,400 deaths were prevented by vaccination, despite modest estimated vaccine effectiveness that season. Like the current 2014-2015 flu season, H3N2 viruses circulated predominantly during the 2012-2013 season.

The fewest deaths prevented by flu vaccination occurred during the 2009 pandemic. Researchers estimated that 222 deaths were prevented by vaccination that season. Study authors attributed this to the fact that 2009 monovalent pandemic vaccine did not become widely available until well after the peak of influenza illness had occurred. Flu activity during the pandemic was dominated by 2009 H1N1 virus circulation, with almost no seasonal viruses being detected during that time.

To conduct the study, researchers applied statistical modeling with U.S. age-group specific estimates of flu-associated excess deaths, monthly flu vaccination coverage estimates, and summary seasonal flu vaccine effectiveness (VE) estimates.

Overall, the findings from the study continue to support the benefits of flu vaccination and suggest that both increased flu vaccination coverage and increased flu vaccine effectiveness would help to prevent more flu-associated deaths.

The article is available online from the Vaccine journal’s website.

 

CDC: Updated Estimated Seasonal Flu Vaccine Effectiveness

 

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By early November (see A `Drift’ In A Sea Of Influenza Viruses) it was becoming obvious that the performance of  this year’s flu vaccine would be negatively impacted by the arrival of a new, `drifted’ H3N2 virus. 

 

At that time, roughly 1/3rd of the viruses tested by the CDC were a poor match for the vaccine – a ratio that would increase to 2/3rds within a month.

 

In early December the CDC issued a HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus, warning that Early Data Suggested A Potentially Severe Flu Season, and recommending the aggressive use of antivirals for high risk patients or those presenting with severe influenza symptoms.

 

With almost all of this year’s flu activity due to H3N2, and 70% of the H3 viruses tested a poor match for the vaccine, it comes as no surprise that this year’s flu vaccine effectiveness (VE) is a fraction of what we usually see (normally in the 50%-60% range).

 

Yesterday the CDC posted the following update, indicating that this year’s VE estimates have dropped to 18% against H3N2, but its effectiveness against Influenza B held at a more respectable 45%.

 

 

CDC Presents Updated Estimates of Flu Vaccine Effectiveness for the 2014-2015 Season

Flu vaccine did not protect against drifted H3N2 viruses, but protected against vaccine-like H3N2 and B viruses

On February 26, 2015, updated interim influenza (flu) vaccine effectiveness (VE) estimates for the current 2014-2015 season were presented to the Advisory Committee on Immunization Practices (ACIP). The updated VE estimate against influenza A H3N2 viruses was 18% (95% confidence interval (CI): 6%-29%).This result is similar to the VE point estimate of 23%, which was reported in a January 16 Morbidity and Mortality Weekly Report (MMWR) and confirms reduced protection against H3N2 viruses this season. The VE estimate against influenza B viruses this season was 45% (95% CI: 14% – 65%).

How well the flu vaccine works can vary depending on a number of factors, including the similarity between circulating influenza viruses and vaccine viruses, and the age, health or immune status of the person vaccinated. The findings for VE against H3N2 viruses this season are about one-third of the VE expected when the flu vaccine is well matched to circulating influenza viruses. The VE against influenza B viruses this season is similar to the effectiveness observed when vaccine viruses and most circulating viruses are well matched.

Reduced protection against H3N2 viruses this season has been attributed to the fact that more than two-thirds of circulating H3N2 viruses analyzed at CDC are drifted from the H3N2 vaccine virus recommended for vaccine production. The proportion of drifted viruses at the U.S. VE study sites was even higher (>80%).

These updated estimates were derived from data collected from the U.S. Flu VE Network from November 10, 2014, through January 30, 2015, and include an additional four weeks of data in comparison to CDC’s early VE estimates released in mid-January.

When VE against all influenza viruses was combined, the overall VE estimate was 19% (95% CI: 7%– 29%). In practical terms, this means the flu vaccine reduced a person’s risk of having to seek medical care at a doctor’s office for flu illness by 19%.

None of the VE estimates by age for this season are statistically significant at this time. Possible explanations for this include: the flu vaccine is having a small effect or there are insufficient samples sizes at this point to produce estimates by age group. Final estimates will be published at the conclusion of the season. It is possible that estimates will change as the season progresses. Influenza activity is declining but remains elevated in the United States and an increasing proportion of influenza B viruses has been detected in recent weeks.

 

 

As we’ve discussed before, there is a pressing need for better flu vaccines (see CIDRAP: The Need For `Game Changing’ Flu Vaccines) -  while far from perfect - the flu shots we have remain the best preventative action you can take against the flu.

Revisiting CIDRAP’s - The Need For Better Flu Vaccines

 

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There’s an accusatory headline, and article, in the UK’s Telegraph today (see Flu vaccine: Ministers may have known of dangerous new strain last March), strongly suggesting that the World Health Organization and other public health entities (including the UK’s PHE) somehow bungled this year’s flu vaccine by not including the new `drifted’ strain’.

 

I guess anytime you can blame the government,  it plays well in Portsmouth, and sells papers.

 

A far more reasonable report can be found on the BBC website, called Why flu vaccines are underperforming this winter, which essentially attributes this year’s vaccine fiasco to `bad luck’.

 

The cause of this consternation is the Eurosurveillance journal report, released yesterday, that calculated an abysmal 3.4% VE (Vaccine Effectiveness) rating for this year’s jab, down from the 50%-60% we normally see.  The inevitable result of this type of vaccine mismatch is a commensurate jump in the number of `excess winter deaths’ – primarily among the elderly.

The problem is, as it has been for more than a half century, that it takes roughly 6 months to produce, prepare, and ship hundreds of millions of doses of flu vaccine, and so the strains to be included must be selected very early in the spring if the vaccine is to be ready by fall.

Complicating matters, while we talk about 2 primary influenza A subtypes (H1N1 & H3N2), in truth there are multiple variations on each in circulation at any given time.   Usually, one of these versions – or clades – dominates over all of the others, but they are constantly playing a viral game of `king of the mountain’, and the balance of power can shift quickly.

 

The change that the Ministers `knew’ about a new strain last March holds little sway when you look back at the Influenza Virus Characterization reports from the ECDC from last spring and summer that described multiple H3N2 variants.

 

While a few of the viruses tested were antigenically different from the vaccine strain, the majority were still a match.

 

Influenza Virus Characterisation, May 2014

• Recently circulating A(H3N2) viruses have fallen within genetic group 3C represented by the recommended vaccine virus for the 2013–14 and 2014–15 seasons, A/Texas/50/2012, with viruses of genetic subgroup 3C.3 predominating. Antigenic analysis using antisera raised against cell-propagated H3N2 viruses indicates that the majority of circulating viruses are antigenically similar to those in circulation in the 2012–13 and 2013–14 influenza seasons.
  
• A small set of viruses in genetic subgroup 3C.3 were not recognised well by the panel of antisera and their HA gene sequences encode several amino acid substitutions compared to other viruses in genetic group 3C.3.

At this point, the components of this year’s vaccine had been `locked in’ for a couple of months, and it was really too late to change. And at this point, it wasn’t at all clear which strain would dominate come the fall.  By September (see ECDC’s Influenza virus characterisation, Summary Europe, September 2014), it was becoming apparent that this new subset of antigenic viruses were on the ascendant, and that report included:

In light of the emergence of antigenically distinct groups of influenza A(H3N2) and the altered
prevalence of influenza B viruses, the WHO recommended composition of influenza vaccines for use in the 2015 southern hemisphere influenza season differed from that recommended for use in the 2014–15 northern hemisphere influenza season.

 

In early November, when I wrote A `Drift’ In A Sea Of Influenza Viruses,  the CDC was still reporting 70% of the  H3N2 viruses tested matched the vaccine component.  Since then, those numbers have fallen to 35% or so.  In Canada, and apparently in Europe as well, those numbers are even lower still.

Twice each year, a group of distinguished influenza scientists gather to try to predict what seasonal flu viruses dominate in six month’s time. 

 

And this year, quite frankly, they guessed wrong.  It happens.  No one has a crystal ball.

One of the big obstacles, of course, is vaccine production time. If vaccine strains could be picked in June or July, and the vaccine produced in 60 days, we’d far see fewer vaccine mismatches.  And that would allow for the timely creation, production, and distribution of an emergency pandemic vaccine as well.

 

But despite a good deal of research, most influenza vaccines are still produced using (admittedly updated) 1950s egg-based technologies.

More than three two years ago, in CIDRAP: The Need For `Game Changing’ Flu Vaccines, we looked at major report – serving as a clarion call for a revolution in vaccine technology - that is as relevant today as the day it was published.

 

Since reports like this one tend to make a big splash, and then are all too quickly forgotten, today seems a good day to revisit that study.

 

The Compelling Need for Game-Changing Influenza Vaccines

An Analysis of the Influenza Vaccine Enterprise and Recommendations for the Future

Michael T. Osterholm, PhD, MPH, Nicholas S. Kelley, PhD, Jill M. Manske, PhD, MPH, Katie S. Ballering, PhD, Tabitha R. Leighton, MPH, Kristine A. Moore, MD, MPH

 

For those not ready to commit to reading a 160-page report, there is a 12-page Executive summary available.

 

At this point I’ll turn to the press release from CIDRAP, where Dr. Osterholm emphasizes the idea that our history of overestimating the effectiveness of the current vaccine serves as a barrier to developing new vaccine technologies.  A bias that perhaps this year, will change.

 

New U of M-led analysis finds urgent need for new influenza vaccines

Laurel Herold, Academic Health Center, 612-624-2449, hero0045@umn.edu
Justin Paquette, Academic Health Center, 612-626-7037, jpaquett@umn.edu

MINNEAPOLIS/ST. PAUL (October 15, 2012) – According to a new report from the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP), current influenza vaccines offer less protection against seasonal influenza than previously reported. As a result, the misperception that current vaccines are highly effective in fighting influenza has become a barrier to creating new, more effective vaccines.

<SNIP>

“We urge people to get their flu shot. The present vaccines are the best interventions available for seasonal influenza,” said Michael T. Osterholm, Ph.D., M.P.H., University of Minnesota infectious disease expert and the CCIVI report’s lead author. “However, these vaccines do not offer consistent, high-level protection – especially in individuals at risk of medical complications or those aged older than 65 years. Unfortunately, these are the populations where we need the vaccines to work the best.  We need new influenza vaccines that work for everyone, most of the time.”

Researchers found that during some influenza seasons, current vaccines offer more protection for most of the population than being unvaccinated. However, compared to most routinely recommended vaccines, influenza vaccine protection is substantially lower.

“We can no longer accept the status quo with regard to influenza vaccine research and development,” added CCIVI expert advisory group chair, Alfred Sommer, Ph.D, Johns Hopkins Bloomberg School of Public Health, after reviewing the latest report. “Only with new game-changing vaccines can we ever really be prepared for the next influenza pandemic.”

(Continue . . .)

 

Despite its limitations, I get the flu vaccine each year, and continue to recommend that others take it as well.  Not because I view it as perfect, or even very good.  At best, it provides a moderate level of protection against the flu – at worst . . . . well, all you have to do is look at this year’s FluView reports.

But however flawed, flu vaccines remain our best protection against a virus that is estimated to kill a half million people around the globe each year. 

 

Like wearing a seatbelt cannot guarantee you’ll walk away from a head-on collision,  a flu vaccine cannot guarantee you won’t get the flu this year.

 

But most years, it reduces your odds of a bad outcome by about half.  And until something better comes along, you use what you can to your best advantage.

MMWR: Reduced Protection From This Year’s Flu Vaccine

Photo Credit - CDC PHIL

 

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It is always a bit of a gamble heading into flu season every year since flu vaccines – whose strains must be selected 6 months in advance – may not end up being a very good match for the viruses that are circulating in the fall. Flu viruses mutate over time – and minor strains that seemed insignificant last spring can become dominant by November. 

 

Such is the the case this year, as a recently arrived, `drifted’ H3N2 flu virus (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus) has come on like gang busters over the past few months, beating out the `vaccine’ strain by a factor of 2 to 1. 

 

The result, as you might expect, is that this year’s flu vaccine isn’t as effective as we’d hoped.

 

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

 

Despite these moderate success levels, studies have shown the benefits of flu vaccination – even if those benefits aren’t as universal, or predictable, as we’d like.

• Last May, in CDC: Flu Shots Reduce Hospitalizations In The Elderly, we saw a study that suggested that even when a vaccine’s effectiveness is low, it can help attenuate the severity of influenza in the elderly.
• Similarly, over the past couple of years, we’ve seen studies suggesting the flu vaccine may reduce the risk of heart attack and stroke (see JAMA: Flu Vaccine and Cardiovascular Outcomes & Study: Flu Vaccine May Reduce Heart Attack). 

 

So, given its limitations, you may be  wondering why I bother to get the flu vaccine every year and recommend it to others.

 

I consider it cheap insurance, even if the shot only offers a moderate degree of protection. Just as wearing a seatbelt doesn’t guarantee you’ll walk away from a wreck, a flu vaccine won’t guarantee you’ll stay flu-free for the season.  But it can improve your odds. 

 

Some years, obviously, more than others.

 

All of which leads up to today’s MMWR report, which carries a mid-season estimate of the effectiveness of this year’s flu vaccine – one that comes in at an admittedly disappointing 23%.

First the CDC’s press release, followed by a link to the MMWR report.

 

Protection from flu vaccination reduced this season

CDC urges early treatment of severely ill and high-risk patients

A report published in the January 16 Morbidity and Mortality Weekly Report (MMWR) estimates that getting a flu vaccine this season reduced a person’s risk of having to go to the doctor because of flu by 23 percent among people of all ages.

Since CDC began conducting annual flu vaccine effectiveness (VE) studies in 2004-2005, overall estimates for each season have ranged from 10 percent to 60 percent effectiveness in preventing medical visits associated with seasonal influenza illness. The MMWR report says this season’s vaccine offers reduced protection and this underscores the need for additional prevention and treatment efforts this season, including the appropriate use of influenza antiviral medications for treatment.

“Physicians should be aware that all hospitalized patients and all outpatients at high risk for serious complications should be treated as soon as possible with one of three available influenza antiviral medications if influenza is suspected, regardless of a patient’s vaccination status and without waiting for confirmatory testing,” says Joe Bresee, branch chief in CDC’s Influenza Division. “Health care providers should advise patients at high risk to call promptly if they get symptoms of influenza.”

One factor that determines how well a flu vaccine works is the similarity between the flu viruses used in vaccine production and the flu viruses actually circulating. During seasons when vaccine viruses and circulating influenza viruses are well matched, VE between 50 and 60 percent has been observed. H3N2 viruses have been predominant so far this season, but about 70 percent of them have been different or have “drifted” from the H3N2 vaccine virus. This likely accounts for the reduced VE.

Flu viruses change constantly and the drifted H3N2 viruses did not appear until after the vaccine composition for the Northern Hemisphere had been chosen.

Another factor that influences how well the flu vaccine works is the age and health of the person being vaccinated. In general, the flu vaccine works best in young, healthy people and is less effective in people 65 and older. This pattern is reflected in the current season early estimates. VE was highest -- 26 percent -- for children age 6 months through 17 years. While not statistically significant, VE estimates for other age groups were 12 percent for ages 18 to 49 years and 14 percent for people age 50 years and older.

CDC recommends that people get a flu vaccine even during season’s when drifted viruses are circulating because vaccination can still prevent some infections and can reduce severe disease that can lead to hospitalization and death. Also, the flu vaccine is designed to protect against three or four influenza viruses and some of these other viruses may circulate later in the season. Flu activity so far this season has been similar to the 2012-2013 flu season, a “moderately severe” flu season with H3N2 viruses predominating.

Antiviral Supply Update

While manufacturers of antiviral medications have stated that there is no national shortage of antiviral medications at this time, and that there is sufficient product available to meet high demand, there are anecdotal reports of spot shortages of these drugs. CDC’s advice for patients and doctors is that it may be necessary to contact more than one pharmacy to fill a prescription for an antiviral medication. Pharmacies that are having difficulty getting orders filled should contact their distributor or the manufacturer directly.

For large institutional outbreaks this season, CDC is taking new measures to help match demand with supply, working with commercial partners to facilitate filling of large orders of antivirals for long-term care facilities or institutions having difficulty accessing antiviral supplies in outbreak settings. More information is available at http://www.cdc.gov/flu/antivirals/supply

 

 

 

Early Estimates of Seasonal Influenza Vaccine Effectiveness — United States, January 2015

Weekly

January 16, 2015 / 64(01);10-15

Brendan Flannery, PhD1, Jessie Clippard, MPH1, Richard K. Zimmerman, MD2, Mary Patricia Nowalk, PhD2, Michael L. Jackson, PhD3, Lisa A. Jackson, MD3, Arnold S. Monto, MD4, Joshua G. Petrie, MPH4, Huong Q. McLean, PhD5, Edward A. Belongia, MD5, Manjusha Gaglani, MBBS6, LaShondra Berman, MS1, Angie Foust, MA1, Wendy Sessions, MPH1, Swathi N. Thaker, PhD1, Sarah Spencer, PhD1, Alicia M. Fry, MD1 (Author affiliations at end of text)

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). Each season since 2004–05, CDC has estimated the effectiveness of seasonal influenza vaccine in preventing medically attended acute respiratory illness (ARI) associated with laboratory-confirmed influenza. This season, early estimates of influenza vaccine effectiveness are possible because of widespread, early circulation of influenza viruses.

By January 3, 2015, 46 states were experiencing widespread flu activity, with predominance of influenza A (H3N2) viruses (2). This report presents an initial estimate of seasonal influenza vaccine effectiveness at preventing laboratory-confirmed influenza virus infection associated with medically attended ARI based on data from 2,321 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (Flu VE) during November 10, 2014–January 2, 2015. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age, sex, race/ethnicity, self-rated health, and days from illness onset to enrollment) against laboratory-confirmed influenza associated with medically attended ARI was 23% (95% confidence interval [CI] = 8%–36%). Most influenza infections were due to A (H3N2) viruses.

This interim VE estimate is relatively low compared with previous seasons when circulating viruses and vaccine viruses were well-matched and likely reflects the fact that more than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014–15 Northern Hemisphere seasonal influenza vaccines (2). These early, low VE estimates underscore the need for ongoing influenza prevention and treatment measures. CDC continues to recommend influenza vaccination because the vaccine can still prevent some infections with the currently circulating A (H3N2) viruses as well as other viruses that might circulate later in the season, including influenza B viruses. Even when VE is reduced, vaccination still prevents some illness and serious influenza-related complications, including thousands of hospitalizations and deaths (3). Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated, including persons who might already have been ill with influenza this season.

(Continue . . .)

A `Drift’ In A Sea Of Influenza Viruses

P&I Mortality Surveillance by Week & Year - CDC

 

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There is always a degree of folly attached to trying to predict the kind of flu season we will have ahead.  The variability in influenza severity can be easily demonstrated by the wide range in the CDC’s mortality estimates, as described in the  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.”

 

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.

 

In other words, even across a span of three decades without seeing an influenza pandemic, there was as much as a 12-fold difference in mortality between flu seasons.  

 

Over the past several years, we’ve seen a huge spread in severity as well, with the 2011-12 flu season perhaps the mildest in three decades (see  2011-2012 Flu Season Draws to a Close), while the following year (2012-13) was deemed moderate-to-severe. 

 

Surprisingly, both were H3N2  dominated seasons, which tend to produce more severe flu seasons – particularly among the elderly (see MMWR Influenza Activity — United States, 2012–13 Season and Composition of the 2013–14 Influenza Vaccine) – proving that `rules of thumb’ don’t always work.

 

Last year we saw the `return’ of the H1N1 strain – which never really went away, but had been dominated by H3N2 since the 2009 pandemic ended. 

 

As is common with H1N1 strains, younger people were more severely impacted than we normally see with H3N2 (see Influenza Activity — United States, 2013–14 Season and Composition of the 2014–15 Influenza Vaccines), prompting a CDC HAN Advisory On Early pH1N1 Influenza Activity to be issued in late December.

 

As far as vaccines are concerned, the 2009 H1N1 component has remained remarkably antigenically stable since it emerged more than five years ago.  We keep expecting to see it drift away from its original form, but so far, it hasn’t.

Less stable have been the H3N2 viruses, which continue to drift and form antigenically diverse clades, which constantly bump shoulders as they seek susceptible hosts. The most recent ECDC: Influenza Characterization – Sept 2014 describes 7 distinct genetic groups detected since 2009, making vaccine strain selection more problematic.

 

Since the fall 2014 vaccines strains were selected last February, surveillance has begun to detect a rise in the number of antigenically drifted H3N2 isolates, prompting the WHO to recommend a strain change for next year’s Southern Hemisphere vaccine formulation from an A/Texas/50/2012 (H3N2)-like virus to an A/Switzerland/9715293/2013 (H3N2)-like virus.

 

According to the CDC’s latest FluView report – while this new, drifted H3N2 strain has begun to show up in North America, for now, this year’s vaccine strain (A/Texas/50/2012(H3N2)) remains dominant  among the limited number of H3N2 viruses tested.

 

CDC has antigenically characterized 10 influenza A (H3N2) viruses collected since October 1, 2014. This is the first antigenic characterization data available for H3N2 viruses collected in the United States since October 1, 2014.

• Seven (70%) of the 10 influenza A (H3N2) viruses tested have been characterized as A/Texas/50/2012-like. This is the influenza A (H3N2) component of the 2014-2015 Northern Hemisphere influenza vaccine. Three (30%) H3N2 viruses were antigenically similar to A/Switzerland/9715293/2013, the H3N2 virus selected for the 2015 Southern Hemisphere influenza vaccine.

Additionally, early surveillance suggests we may be looking at an H3N2-centric flu season.

 

Influenza A (H3N2), 2009 influenza A (H1N1), and influenza B viruses have all been identified in the U.S. this season. During the week ending October 25, 237 (74.1%) of the 320 influenza-positive tests reported to CDC were influenza A viruses and 83 (25.9%) were influenza B viruses. Of the 82 influenza A viruses that were subtyped, 96% were H3 viruses and 4% were 2009 H1N1 viruses.

 

Again, flu seasons don’t always end up the way they start out. 

 

But for now, it looks as if we may be looking at a flu season dominated by H3N2, and with two antigenically divergent clades in circulation.  One `covered’ by the this year’s vaccine, and the other – well, probably not so much.

 

None of which is to suggest that this year’s flu vaccine isn’t worth getting (I’ve already gotten mine), or that a mismatched vaccine offers no protection against an antigenically divergent virus.   The CDC explains:

 

What if there is a mismatch between circulating viruses and the vaccine viruses?

A “mismatch” is said to occur when the viruses in the vaccine are significantly different from those circulating in the community. In years when the vaccine strains are not well matched to circulating strains, vaccine effectiveness can be reduced. However, even when the viruses in the vaccine and circulating viruses are not well matched, a vaccine may still offer some protection against circulating viruses.

For example, in a study among persons 50-64 years of age during the 2003-04 influenza season, when the vaccine strains were not optimally matched, inactivated influenza vaccine effectiveness against laboratory-confirmed influenza was 60% among persons without high-risk conditions, and 48% among those with high risk conditions. However, vaccine effectiveness was 90% against laboratory-confirmed influenza hospitalization (Herrera, et al Vaccine 2006). A study in children during the same year found vaccine effectiveness of about 50% against medically diagnosed influenza and pneumonia without laboratory confirmation (Ritzwoller, Pediatrics 2005). Still, in some years when vaccine and circulating strains were not well-matched, no vaccine effectiveness may be able to be demonstrated (Bridges, JAMA 2000). It is not possible in advance of the influenza season to predict how well the vaccine and circulating strains will be matched, and how that may affect vaccine effectiveness. For more information, see Vaccine Effectiveness - How Well Does the Flu Vaccine Work?

 

Although a partially mismatched vaccine, and an H3 heavy year may suggest a severe flu season ahead, how all of this will play out, is unknown. Which is why the CDC issues a mid-season and end-of-season reports rather than a forecast.

 

As I’ve written here often , flu vaccines are considered very safe – and most years provide a moderate level of protection against influenza. 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.

 

While the vaccine can’t promise 100% protection, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – remains your best strategy for avoiding the flu (and other viruses) this winter.

ECDC: Influenza Characterization – Sept 2014

Credit NIAID

 

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Although we tend to talk of seasonal H1N1, or H3N2 (or the B viruses) as individual entities – in truth within each subtype there are many clades and variants, and they are all evolving over time. The more `biologically fit’ strains tend to succeed, while less fit viruses fade away. 

 

Geographically, these viruses can vary widely, and so the dominate strains in Europe may differ from the dominant strains in North America or Asia.

 

Success for these strains is always fleeting, though,  as they leave behind varying degrees of immunity in their hosts and must either evolve or eventually die out for lack of susceptible hosts. 

 

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.

As flu vaccine formulations must be decided upon six months in advance of each flu season, public health agencies like the CDC, ECDC, the World Health Organization, Hong Kong’s CHP  (and others) spend considerable resources on influenza surveillance, looking for signs of any up-and-coming viral strains.

 

All of which brings us to the ECDC’s latest influenza virus characterization summary, that looks at the ongoing evolution of these seasonal strains over the past few months. As you will see, there are changes in the evolving fluscape that have necessitated a change to the next year’s Southern Hemisphere Flu shot composition.

 

Detailed PDF file

 

Influenza virus characterisation, Summary Europe, September 2014

During the 2013–14 season, A(H1N1)pdm09, A(H3N2), B/Victoria- and B/Yamagata-lineage influenza viruses co-circulated in EU/EEA Member States. The relative prevalence has varied between countries. The WHO Collaborating Centre in London received viruses with collection dates after 31 January 2014 from 21 EU/EEA countries.

Type A and type B viruses have been received at a ratio of approximately 10:1. A(H3N2) outnumbered A(H1N1)pdm09 viruses at a ratio of 1.4:1.

Recently circulating A(H1N1)pdm09 viruses, in Europe and worldwide, belonged to genetic subgroup 6B. Viruses in this subgroup are antigenically similar to the vaccine virus, A/California/07/2009.

Recently circulating A(H3N2) viruses have fallen within genetic group 3C represented by the recommended vaccine virus for the 2013–14 and 2014–15 seasons, A/Texas/50/2012. Antigenic analysis using antisera raised against cell-propagated H3N2 viruses indicates that the majority of circulating viruses are antigenically similar to those in circulation in the 2012–13 and 2013–14 influenza seasons, but those in a newly emerging genetic cluster, 3C.3a, are poorly recognised by some antisera.

Two genetic clades of B/Yamagata-lineage viruses continue to circulate: clade 3 represented by B/Phuket/3073/2013 and clade 2 represented by B/Massachusetts/02/2012 (the recommended vaccine component for the 2013–14 and 2014–15 influenza seasons). Viruses in clade 3 predominate in those samples collected since 31 January 2014.

Only two viruses of the B/Victoria-lineage were antigenically characterised since the July 2014 report. Neither was recognised well by the antiserum raised against the egg-propagated reference virus, A/Brisbane/60/2008, recommended as a component of quadrivalent influenza vaccines for 2013–14 and 2014–15 influenza seasons. Phylogenetic analysis revealed that all B/Victoria-lineage viruses received in 2014 were in genetic clade 1A, the B/Brisbane/60/2008 genetic clade.

In light of the emergence of antigenically distinct groups of influenza A(H3N2) and the altered prevalence of influenza B viruses, the WHO recommended composition of influenza vaccines for use in the 2015 southern hemisphere influenza season differed from that recommended for use in the 2014–15 northern hemisphere influenza season.

 

Remarkably, the H1N1 strains in circulation remain very stable, and antigenically similar to the vaccine virus which has been unchanged for five years (A/California/07/2009).  

The situation with the H3N2 viruses is more variable, with 7 distinct genetic groups detected since 2009, making vaccine strain selection more problematic. 

 

Since the fall 2014 vaccines strains were selected last February, surveillance has detected a rise in the number of antigenically drifted H3N2 isolates, prompting the WHO to recommend a strain change for next year.

The same can be said for recent detections of the Influenza B – Yamagata lineage of viruses, and so the WHO is recommending a change next year for the vaccine as well. 

How all of this will affect the performance of this year’s flu vaccine in the Northern Hemisphere is unknown.  If we see a heavy H1N1 year, then probably not much. Nor does the detection of these divergent strains in Europe guarantee when, or even if, we’ll see the same strains in North America.

 

There is always a degree of uncertainty over how good a match the vaccine will be when we enter a new flu season. But even when there is a less than a perfect match – the flu shot can offer significant levels of protection against a virus that claims thousands of American lives every year.  

 

As we’ve discussed before, flu vaccines – while considered very safe – most years can only offer a moderate level of protection against influenza. 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.

 

Although the vaccine can’t promise 100% protection, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – remains your best strategy for avoiding the flu (and other viruses) this winter.

CDC: Flu Shots Reduce Hospitalizations In The Elderly

Photo Credit - CDC PHIL

 

 

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Although the elderly (> 65) are considered to be the most endangered by influenza infection, they are also the group least likely to be protected by the seasonal flu vaccine (see PLoS One: Limited Effectiveness Of Flu Vaccines In The Elderly & Flu Shots And The Elderly).

 

That isn’t to say the flu vaccine is worthless, or not worth bothering with – only that the amount of protection for the elderly is generally less than for other age cohorts.

 

In 2011,  NFID - the National Foundation for Infectious Diseases - convened a group of experts to address the issues of influenza and the elderly. From that panel a 5-page brief has emerged, called: Understanding the Challenges and Opportunities in Protecting Older Adults from Influenza.

This report pointed out that 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.

Similarly, over the past couple of years, we’ve seen studies suggesting the flu vaccine may reduce the risk of heart attack and stroke (see JAMA: Flu Vaccine and Cardiovascular Outcomes & Study: Flu Vaccine May Reduce Heart Attack).  .

 

Yesterday, the CDC announced the results of a study published in Clinical Infectious Diseases.  First a link to the study, then some excerpts from the CDC statement.

 

Modeling the effect of different vaccine effectiveness estimates on the number of vaccine prevented influenza associated hospitalizations in older adults

Alicia M. Fry1, Inkyu K. Kim1,2, Carrie Reed1, Mark Thompson1, Sandra S. Chaves1, Lyn Finelli1, and Joseph Bresee1

Abstract

We compared influenza vaccine-prevented hospitalizations in adults aged>65 years for a range of hypothetical effectiveness estimates. During 2012-13, a vaccine with 10% effectiveness (66% coverage)would have averted ∼13,000 hospitalizations and a vaccine with 40% effectiveness would have averted ∼60,000 hospitalizations.Annual vaccination is merited in this vulnerable population.

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This from the http://www.cdc.gov/flu website.

 

CDC Study Concludes Flu Vaccination Prevents Hospitalizations in Older People

Hospitalizations averted even when vaccine effectiveness is lower

May 9, 2014 – A new CDC study shows that flu vaccines prevent flu-associated hospitalizations in people 65 years and older, even during seasons when vaccine effectiveness is low. The study reinforces CDC’s existing recommendation for annual vaccination of adults 65 years and older who are at high risk for serious flu-related complications and often most impacted by serious flu disease each year resulting in hospitalization or death.

The study, published in Clinical Infectious Diseases online on May 6, 2014, used statistical modeling to estimate flu-vaccine-prevented hospitalizations in adults aged 65 years and older for estimates of vaccine effectiveness against medically attended influenza illness ranging from 10% to 70%. Researchers used CDC flu surveillance data collected during the 2011-12 and 2012-13 seasons. The 2011-12 season was considered to be a mild flu season, whereas the 2012-13 season was characterized as moderate to severe. Using data from these two seasons, researchers were able to determine the varying impact that flu vaccination had in terms of hospitalizations prevented.

Findings showed that during the more severe 2012-13 flu season, a flu vaccine with 10% effectiveness (and 66% coverage) would avert about 13,000 hospitalizations, whereas a vaccine with 40% effectiveness would avert about 60,000 hospitalizations. In contrast, during the more mild 2011-12 season, a flu vaccine with the same two effectiveness estimates would avert about 2,000 and 11,000 hospitalizations, respectively.

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Despite disappointing VE (Vaccine Effectiveness) numbers (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis) - particularly among the elderly (see BMC Infectious Diseases: Waning Flu Vaccine Protection In the Elderly) - we continue to see evidence of benefit from the shot, even if full protection isn’t conveyed to the recipient.

 

As addressed back in 2012 by CIDRAP: The Need For `Game Changing’ Flu Vaccines, there is obviously a great need for better, more effective, and faster to the market flu vaccines.  But even with their current limitations -  I certainly get one each year -  and I urge others to do the same.

 

Not because it is guaranteed protection . . . .

 

But because – like wearing a seatbelt during a motor vehicle crash  – it substantially improves your odds of a good outcome.

Branswell On Low Flu Vaccine Effectiveness In 2012-13 Flu Season

 

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Helen Branswell has the story on a PLoS One study, published yesterday, that found an unusual `production issue’ with last year’s seasonal flu vaccine that resulted in a disappointing level of protection against the H3N2 virus.

 

The open access study is called:

 

Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses

Danuta M. Skowronski mail, Naveed Z. Janjua, Gaston De Serres, Suzana Sabaiduc, Alireza Eshaghi, James A. Dickinson, Kevin Fonseca, Anne-Luise Winter, Jonathan B. Gubbay, Mel Krajden, Martin Petric, Hugues Charest, Nathalie Bastien,  [ ... ], Yan Li

 

As you might imagine, this is a fairly complex report, so we can be thankful that Helen does such a terrific job deciphering it all for us.  Follow the link to read:

 

Flu vaccine production issue may be behind last year's modest protection: study

Helen Branswell / The Canadian Press
March 25, 2014 02:20 PM

ORONTO - The 2012-13 influenza season was a harsh one, and one in which flu vaccine offered disappointingly modest protection against the main circulating strain, H3N2.

The limited protection — around 41 per cent for healthy adults and a mere nine per cent for seniors — was surprising, given that the H3N2 viruses causing illness were a close match for one the World Health Organization had selected for inclusion in that winter's vaccine.

New Canadian research is offering an explanation for that puzzling and unfortunate phenomenon. It reveals that the H3N2 component that went into the vaccine wasn't exactly what the WHO's experts ordered.

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In her report, Helen quotes Michael Osterholm of Director of CIDRAP, who has long held that that big changes are needed in the way we manufacture vaccines.

 

These issues were the topic of a blog back in the 2012 called CIDRAP: The Need For `Game Changing’ Flu Vaccines – which looked at a truly impressive 160-page CIDRAP report that emphasizes the need for a revolution in vaccine technology.

 

The Compelling Need for Game-Changing Influenza Vaccines

An Analysis of the Influenza Vaccine Enterprise and Recommendations for the Future

Michael T. Osterholm, PhD, MPH, Nicholas S. Kelley, PhD, Jill M. Manske, PhD, MPH, Katie S. Ballering, PhD, Tabitha R. Leighton, MPH, Kristine A. Moore, MD, MPH

For those not ready to commit to reading a 160-page report, there is a 12-page Executive summary available.

 

CDC Research On Benefits Of Antivirals For Uncomplicated Influenza

Photo Credit – Wikipedia

 

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In clinical medicine there are a lot of things that we think we know – based on observational studies – but for which rigorous randomized controlled trials (RCTs) have not been conducted. Sometimes it is impractical (or even unethical) to subject patients to an RCT, especially if it involves withholding a potentially lifesaving drug from a `control’ cohort.

 

So we are often left to rely on less desirable, but still useful, observational studies to gauge the value of treatments or therapies.

 

Over the past decade one of the drugs that has fallen into this pharmaceutical limbo is oseltamivir (Tamiflu ®), a product of Roche laboratories, which has been stockpiled by many nations to combat a flu pandemic.  Observational studies have shown that this drug can significantly reduce morbidity and  mortality in severe cases of flu, and modestly reduce the duration of symptoms in uncomplicated seasonal flu.

But robust RCTs have not been conducted to quantify these benefits, and `RCT purists’ like this Cochrane group analysis – that do not consider `observational studies’ to be solid evidence - have found insufficient evidence to show whether the drug reduces influenza complications and transmission (see 2012 CIDRAP article Review renews questions about oseltamivir benefits).

 

Add to this 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, and the result has been 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). 

 

With a new avian (H7N9) virus in the wings and H5N1 still simmering in Asia and the Middle East, the CDC recently reiterated their support for the use of oseltamivir in the treatment of severe, or novel, influenza infection (See H7N9: Updated CDC Guidance For Antiviral Treatment).

 

Yesterday, the CDC published a news release on an RCT conducted in Bangladesh on the benefits of Oseltamivir in uncomplicated seasonal flu.  A category of illness where one would expect the least amount of benefit to taking an antiviral. A few excerpts, and a link to The Lancet Study, then I’ll return with a bit more.

 

CDC Research Confirms Benefits of Flu Antiviral Drugs, Even Beyond 2 Days After Symptoms Start

New research confirms benefits of the influenza antiviral medication oseltamivir in treating children with uncomplicated flu illness and shows that treatment can be beneficial even beyond the two-day window recommended as a cut-off for treatment in the drug’s package insert.

A new study on influenza (flu) antiviral drugs by CDC authors was released today in The Lancet Infectious Diseases. This study is the first clinical trial to note a significant reduction in the duration of illness and virus shedding in children when influenza antiviral treatment was initiated more than 2 days after the onset of influenza (flu) symptoms. These findings confirm the benefits of using the antiviral drug oseltamivir to treat flu illness and suggest that some children will benefit when treatment is initiated beyond 2 days, which is the recommended cut-off for treatment in the current package insert.

 

The patients in this double-blind, randomized, placebo-controlled study were mostly children (average age: 5 years) in an urban setting in Bangladesh with laboratory-confirmed influenza infection and no additional flu-related complications. Patients were treated with either oseltamivir (a type of flu antiviral drug known as a “neuraminidase inhibitor”) or a placebo (e.g., a shot of saline). Researchers observed when patients began oseltamivir treatment — either less than 48 hours or 48 hours or more after illness onset — and collected information about the duration of flu symptoms using standardized forms collected from daily household visits. In addition to documenting the duration of flu symptoms, researchers also measured viral shedding, which is virus detection at various times after the patients were enrolled. The detection of live virus in respiratory secretions is thought to be associated with how contagious a person is to others.

 

Among all children receiving oseltamivir within 5 days of illness onset, researchers found that overall flu symptoms were reduced by one day compared with those treated with placebo (3 days versus 4 days). This finding is consistent with results from other flu antiviral studies that started treatment within 2 days of illness onset. The results also show that oseltamivir treatment reduced the amount of live virus that was isolated from respiratory specimens by 12% to 50% compared with placebo regardless of whether treatment was started before or after 2 days since illness onset. This finding is especially important because no other study has shown reduced viral shedding in similar proportions regardless of whether treatment is started less than or more than 48 hours after flu symptoms begin.

(Continue . . . )

The article is available in The Lancet Infectious Diseases: “Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial.”

 

 

Of course, governments aren’t stockpiling Tamiflu for uncomplicated seasonal flu.  They have purchased millions of doses in anticipation of a severe pandemic.  And while RCTs on treating severe influenza with the drug are scant, we have seen some pretty compelling observational and anecdotal data.

 

In 2010 an observational study appearing in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) strongly suggested that Tamiflu was life saving for some patients with pandemic flu. And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

In December of 2012, in Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic we looked at a meta-analysis of 90 observational studies that appeared in the Journal of Infectious Diseases that spanned nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.

 

Their main finding was antiviral therapy - principally oseltamivir - initiated within 48 hours of onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%.

 

And lastly, for those who question the value of Tamiflu in an avian flu pandemic, in Study: Antiviral Therapy For H5N1, we saw the largest study to date on outcomes of H5N1 patients who either received, or did not receive, antiviral treatment. The research appears in the IDSA’s  Journal of Infectious Diseases. The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

 

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

While today’s study may not completely mollify the critics, the preponderance of evidence continues to show that antivirals – including Tamiflu – can have a substantial positive therapeutic effect on influenza, particularly in high risk patients.

PLoS One: Limited Effectiveness Of Flu Vaccines In The Elderly

 

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A topic we’ve covered often in the past has been the limited effectiveness of influenza vaccines among the elderly (>=65) (see Flu Shots And The Elderly, NFID: The Challenges Of Influenza In Older Adults, BMC Infectious Diseases: Waning Flu Vaccine Protection In the Elderly)  or those with compromised or suppressed immune systems.  Those populations most endangered by influenza are, unfortunately, the least likely to be protected by the flu vaccine.

That isn’t to say the flu vaccine is worthless, or not worth bothering with. 

I get the flu shot every year, and I encouraged my Dad to get one until he died at the age of 87, even knowing its limitations.  When dealing with a potentially life threatening illness . . . some protection beats no protection, any day of the week.  

 

But, like seat belts, flu shots can only offer so much protection.  For healthy adults under the age of 65, flu shots are generally described as being moderately effective. 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.

 

Also in 2011,  NFID - the National Foundation for Infectious Diseases - convened a group of experts to address the issues of influenza and the elderly. From that panel a 5-page brief has emerged, called: Understanding the Challenges and Opportunities in Protecting Older Adults from Influenza.

 

 

 

Yesterday the open access journal PLoS One published a new retrospective study conducted in Ontario, Canada that attempts to quantify the level of protection those over the age of 65 received from seasonal influenza vaccination.  Not surprisingly, they found that the VE (vaccine effectiveness) to be considerably lower than what has been seen with younger adults.

 

Research Article

Effectiveness of Inactivated Influenza Vaccines in Preventing Influenza-Associated Deaths and Hospitalizations among Ontario Residents Aged ≥65 Years: Estimates with Generalized Linear Models Accounting for Healthy Vaccinee Effects

Benjamin J. Ridenhour mail,Michael A. Campitelli, Jeffrey C. Kwong, Laura C. Rosella, Ben G. Armstrong, Punam Mangtani, Andrew J. Calzavara, David K. Shay

Abstract

Background

Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications.

Methods

We conducted a retrospective cohort study among Ontario residents aged ≥65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations.

Results

During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥65 years was 22% (95% confidence interval [CI], −6%–42%) for all influenza-associated deaths, 25% (95% CI, 13%–37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%–31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively.

Conclusions

By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ~4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.

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Those whose eyes don’t bleed when reading about complex statistical methods will want to peruse the entire study. In an act of self preservation, I admit I only skimmed those areas. The bottom line is that by using statistical analyses far above my pay grade, these authors have determined that the seasonal flu vaccine had about a 22% VE rating for those over the age of 65.

 

In an accompanying press release from the University of Notre Dame, we get the following summation.

 

Notre Dame researchers look at benefits of flu vaccines in the elderly

Sarah Craig

October 16, 2013

(EXCERPT)

In their central findings of the research, the authors said, “By combining health data with climate data and developing novel statistical analyses, we found that vaccination was 19 percent effective at preventing pneumonia- or influenza-related hospitalizations and 25 percent effective at preventing death occurring subsequent to a pneumonia- or influenza-related hospitalization.”

The results indicate that, over a long time period, the influenza vaccine has performed worse than expected in elderly individuals, thus proving the need for improvements in influenza vaccine development.

(Continue . . . )

 

If that last observation sounds familiar, it is likely because it echo’s the sentiments of last year’s major report (see CIDRAP: The Need For `Game Changing’ Flu Vaccines).

 

The Compelling Need for Game-Changing Influenza Vaccines

An Analysis of the Influenza Vaccine Enterprise and Recommendations for the Future

Michael T. Osterholm, PhD, MPH, Nicholas S. Kelley, PhD, Jill M. Manske, PhD, MPH, Katie S. Ballering, PhD, Tabitha R. Leighton, MPH, Kristine A. Moore, MD, MPH

 

For those not ready to commit to reading a 160-page report, there is a 12-page Executive summary available.

 

While today’s study provides a disappointing result, and highlights the need for developing better influenza vaccines, the bottom line is that the current vaccine was found to be  `25 percent effective at preventing death occurring subsequent to a pneumonia- or influenza-related hospitalization’. 

 

Given the toll that influenza takes on the elderly, that 25% survival advantage has to be viewed as being better than no advantage at all.