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.

 

Hong Kong Prioritizes Groups To Receive Emergency Flu Vaccine

 

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The effect of this year’s vaccine mismatch due to a `drifted’ H3N2 virus has been keenly felt across the Northern Hemisphere, but perhaps no more so than in Hong Kong which has seen a doubling of severe cases and a tripling of deaths over last season. 

 

While the flu season is slowly winding down for most of us, Hong Kong continues to report new deaths daily, and historically often endures a second peak of influenza in the summer (see Hong Kong Girds For More Flu).

HK’s recent history of `Twin Peaks’ of influenza– Credit Flu Express

 

Although the Northern Hemisphere flu vaccine was a bust this year, the re-formulated Southern Hemisphere vaccine is due out in the next few weeks, and it includes a strain that should match the `drifted’ H3N2.   In an unusual move,  Hong Kong’s CHP announced last February they had ordered a limited supply of the New Southern Hemisphere flu vaccine (SH SIV), which was expected to arrive in April.

 

With a population of over 7 million, of which roughly 13% (1 million) are over the age of 65, and only about 100, 000 doses of this new vaccine expected to be available, Hong Kong has had to make the kind of vaccine prioritization decisions that we might expect to see in the opening months or year of a pandemic; deciding who gets part of limited resource.

 

Since 1.7% of the city’s population – those 85 and older – comprise 53% of this year’s influenza deaths, that cohort will have top priority when the new vaccine arrives (see HK Demographics Chart).  Whatever vaccine remains after this first tier is served will be used for those aged 75-84, although depending on uptake, supplies are likely to fall short of that cohort’s needs.

 

Despite the original April target delivery date, it now appears this vaccine won’t be deployed until May or June.

 

This from Hong Kong’s CHP:

 

Scientific Committee recommends priority groups to receive southern hemisphere influenza vaccine

The Controller of the Centre for Health Protection (CHP) of the Department of Health (DH), Dr Leung Ting-hung, today (March 20) welcomed the recommendations on the use of the southern hemisphere seasonal influenza vaccine (SH SIV) by the CHP's Scientific Committee on Vaccine Preventable Diseases (SCVPD) in Hong Kong.

"The SH SIV contains the currently predominant influenza A/Switzerland/9715293/2013 (H3N2)-like virus strain. Based on the risk assessment, the SCVPD recommends the elderly to be the priority group to receive the SH SIV to protect them from the possible summer influenza season. Besides, the SCVPD recommends all persons living in residential care homes for the elderly (RCHEs) to receive the SH SIV for the prevention of influenza outbreaks," Dr Leung said.

Epidemiology and priority groups

The SCVPD convened two meetings respectively on February 17 and this morning to examine the latest local, neighbouring and overseas epidemiology of seasonal influenza in this winter season, and assess the risk of various groups. It also studied issues related to the use of the SH SIV, including vaccine composition, vaccine effectiveness, any adverse effects and priority groups.

"The elderly, particularly the very old elderly, are the most vulnerable in this season as reflected by the high proportion of severe and fatal cases affecting the elderly, the high influenza admission rate among the elderly and the high proportion of RCHEs having outbreaks of influenza-like illness (ILI)," Dr Leung explained.

As of noon of March 16, among influenza-associated admissions to intensive care unit or deaths in adults aged 18 or above under the enhanced surveillance with public and private hospitals since January 2, 86.0 per cent were the elderly aged 65 or above (41.4 per cent aged 85 or above, 31.3 per cent aged 75 to 84, 13.2 per cent aged 65 to 74). As for deaths, 93.5 per cent were those aged 65 or above (53.0 per cent aged 85 or above, 31.7 per cent aged 75 to 84, 8.8 per cent aged 65 to 74).

The influenza-associated public hospital admission rate for the elderly aged 65 or above peaked at 5.54 cases per 10 000 persons in the last week of January, which is the highest since 2005, and has remained elevated so far. Institutional ILI outbreaks in this season mainly occurred in RCHEs (over 40 per cent).

"The SH SIV, when available, may be given by phases starting from the oldest age group, such as those aged 85 or above, in the community first as they are at higher risk of developing severe illness after infecting influenza. Most of them also have pre-existing underlying illnesses predisposing them to severe illness," Dr Leung remarked.

Programme arrangements

The DH has procured about 100 000 doses of SH SIV from a vaccine supplier by contract upon completion of the tender in accordance with government procurement procedures and requirements. As they are expected to be delivered in late April or early May, the vaccination programme is preliminarily planned to be conducted in May and June.

"Vaccination will be provided to priority groups, i.e. the elderly, under the existing Government Vaccination Programme (GVP) for free. As part of the GVP, the Residential Care Home Vaccination Programme will provide the SH SIV to RCHEs' residents through enrolled Visiting Medical Officers to which an injection fee of $50 per dose will be reimbursed. We will work out the logistics with RCHEs shortly," Dr Leung said.

Regarding the elderly in the community setting, the CHP is working closely with the Hospital Authority on the implementation. The elderly will receive the SH SIV by phases in public hospitals and clinics, with those of higher age to be vaccinated first, followed by other elderly in the next.

Ends/Friday, March 20, 2015
Issued at HKT 13:33

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.

JCI: Preexisting Human Antibodies Neutralize H7N9 influenza strains

 

Credit NIAID

 

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Based on some of the press coverage overnight (see below) one could be forgiven for coming away with the impression that if you’ve gotten the flu shot recently, you are probably immune to the avian H7N9 flu.

 

But of course, things are never as simple as the headline writers would have us believe.

First, this excerpt from Agence France-Presse.

 

Flu shot protects against new strain H7N9: study

February 18, 2015 12:02pm

29 7 0 38

The flu vaccine may not have protected most people against influenza circulating widely this season, but a study Tuesday showed it was effective against the new H7N9 strain that emerged in China in 2013.

(Continue . . .)

Pretty definitive, and this story provides little in the way of caveats, although at one point (near the end) it quotes study author Carole Henry as saying,  "Although they are not always protective, H7-reactive antibodies can be found in almost everyone that's been vaccinated."

Not mentioned in this report, however, are the sticky little details that the level of  H7N9 cross-reactive antibodies created by the seasonal flu shot are fairly low, and the amount of protection they would convey to humans is unknown.

While we are reassured that  `three antibodies appeared to completely neutralize H7N9 avian flu’, less clear are the facts that these antibodies were only tested in vitro and in mice. 

 

While valid test methods, neither are fully predictive of human physiological responses.

 

Despite the media’s ambitious interpretation, the study makes no claims as to the level of serum protection in the general population against H7N9 due to previous flu vaccinations.

 

A far more balanced report on this study can be found on Live Science, by Rachel Rettner (see Flu Shot May Give You a Boost Against Bird Flu), where she quotes one of the study’s authors:

 

Still, it's not known whether the level of antibodies seen in the study participants would be enough to provide full protection against an H7N9 infection. Wilson said he suspects that vaccination with a seasonal flu shot would not fully protect against H7N9, but that if those vaccinated did become infected with the virus, these "cross reactive" antibodies might improve their situation, for example, by reducing how long they are sick or how ill they become.

 

In other words, a history of taking the seasonal flu vaccine might provide an `edge’ against novel flu infection that someone with a more immunologically naive system might not have.  

 

The key finding here is not that we are all already protected against H7N9, but that the seasonal flu shot generates small amounts of broadly neutralizing  antibodies which – if preferentially amplified – might lead to more effective therapies against a broad range of novel flu strains.  

 

As an added bonus, some of us may already carry some small level of cross-reactive antibodies which might help reduce the impact of an H7N9 infection.

 

From a University of Chicago press release:

 

Seasonal flu vaccine induces antibodies that protect against H7N9 avian flu

Study identifies antibodies isolated from individuals with seasonal flu vaccinations that neutralize H7N9 and other influenza strains

February 17, 2015

(EXCERPT)

Despite the efficacy of these antibodies, it is still unclear why they are produced in relatively low amounts. The team is now working to better understand this process and to develop therapeutic approaches based on these antibodies.

"The challenge is to exploit this response on a larger scale to make vaccines or therapeutics that offer broad protection against influenza strains," Wilson said. "For now, it's clear that seasonal flu vaccination provides defense against more than just common strains. Everyone should be vaccinated."

(Continue . . .)

 

Below is a link to the actual study, which is available in its entirety online.

 

Preexisting human antibodies neutralize recently emerged H7N9 influenza strains

Carole J. Henry Dunand¹, Paul E. Leon^2,3, Kaval Kaur^1,4, Gene S. Tan², Nai-Ying Zheng¹, Sarah Andrews¹, Min Huang¹, Xinyan Qu¹, Yunping Huang¹, Marlene Salgado-Ferrer¹, Irvin Y. Ho¹, William Taylor¹, Rong Hai², Jens Wrammert⁵, Rafi Ahmed⁵, Adolfo García-Sastre^2,6,7, Peter Palese^2,6, Florian Krammer² and Patrick C. Wilson^1,4

Published February 17, 2015
Submitted: July 21, 2014; Accepted: January 6, 2015.

The emergence and seasonal persistence of pathogenic H7N9 influenza viruses in China have raised concerns about the pandemic potential of this strain, which, if realized, would have a substantial effect on global health and economies. H7N9 viruses are able to bind to human sialic acid receptors and are also able to develop resistance to neuraminidase inhibitors without a loss in fitness. It is not clear whether prior exposure to circulating human influenza viruses or influenza vaccination confers immunity to H7N9 strains.

Here, we demonstrate that 3 of 83 H3 HA-reactive monoclonal antibodies generated by individuals that had previously undergone influenza A virus vaccination were able to neutralize H7N9 viruses and protect mice against homologous challenge. The H7N9-neutralizing antibodies bound to the HA stalk domain but exhibited a difference in their breadth of reactivity to different H7 influenza subtypes. Mapping viral escape mutations suggested that these antibodies bind at least two different epitopes on the stalk region.

Together, these results indicate that these broadly neutralizing antibodies may contribute to the development of therapies against H7N9 strains and may also be effective against pathogenic H7 strains that emerge in the future.

(Continue . . . )

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.

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Italy: AIFA Investigating Deaths Among Flu Vaccine Recipients

 

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Flu vaccines have a long and enviable history of safety, and while side effects have been reported, serious reactions are very rare.  But no vaccine, or any other drug or medicine for that matter, is 100% safe or benign. 

 

Complicating matters, drugs and vaccines are often used by the elderly or those with pre-existing medical problems, making it difficult to sort out the cause whenever an untoward medical event occurs. 

 

This weekend, in Italy, officials are trying to determine if two specific lots of Novartis flu vaccine played any role in the recent deaths of a number of (mostly) elderly vaccine recipients.  Right now, there is no proof that the vaccines are at fault, but the use of two lots of the vaccine has been temporarily suspended.  

 

First, a status report from the Italian Pharmaceutical Agency (AIFA), followed by statements by Novartis, and by the European Medicines Agency.

 

Fluad vaccine. The AIFA takes stock of the situation

Twelve reports of deaths after vaccination received to date. 8000 people die each year from the consequences of influenza

29/11/2014

The AIFA informs that after the ban on the use of lots 143 301 and 142 701 vaccine Fluad after reporting three deaths occurred between 7 and 18 November, yesterday were included eight other reports (deaths occurring between 15 and 28 November ) of which the Agency has requested a detailed clinical report that so far has not yet been received for any of them.

In the day today has been registered in the National Network of Pharmacovigilance (RNF) a new death occurred on November 24, and yesterday received a 'e-mails on a death that has yet to be verified. The total number of cases reported through the RNF is therefore 12. A first analysis of these signals allows to draw the following conclusions exclusively preliminary:

• In 8 cases (67%) seen in people aged ≥ 80 years.
• 7 cases are female and 5 male gender.
• In eight cases death occurred in the first 24 hours.
• In eight cases death occurred from cardiovascular causes.
• The reports concern 6 Regions: Sicily (2); Molise (1); Puglia (2); Tuscany (2); Emilia Romagna (2); Lombardy (2); Lazio (1).
• The lots involved have passed from 2 to 6 for a total of 1,357,399 doses.
• The signals are received by the RNF with a time range from immediate (same day of death) to 13 days later.
• If all of the doses of these 6 lots had been administered, the percentage of deaths would rise from 0,001% (1.2 each 100.00) at 0.0009% (0.9 each 100.00) with a dilution of 25% of the signal.
• If it had been given even half the number of deaths would be hundreds of times less than expected in the same non-vaccinated population (about 8,000 deaths per year for flu complications).

The AIFA confirms the correlation time for suspected cardiovascular events in the first 24 hours after administration in patients suffering from over eighty polypathology and polypharmacy. The Fluad however expressly indicated in this population

(Continue . . .)

 

This from Novartis:

 

Safety and efficacy of Fluad vaccinations in Italy

November 28, 2014 18:00 CET

Regarding the precautionary suspension of two batches of Fluad® in Italy, Novartis underlines that no causal relationship to the vaccine has been established to date.

Fluad is approved for vaccination of elderly patients (65+) and often prescribed to patients who suffer from pre-existing underlying medical conditions and have a weaker immune system. Serious medical events and deaths are unfortunately quite common in this patient population and hence a coincidental timely association with vaccination is not unusual.

The two suspended batches comprising of 500,000 doses were distributed solely in Italy after having passed all required safety and quality testing, including review by regulatory authorities before release to market.

Worldwide, more than 7 million doses of Fluad have been distributed. No unusual frequency of adverse events has been reported through the extensive pharmacovigilance system.

Fluad is an important vaccine to protect the elderly from influenza. They are at high risk of serious complications from influenza infections. In Europe alone, the death toll is estimated at 40,000 each year. Fluad was licensed in 1997 and has a solid safety history. The vaccine has been tested in clinical trials with 70,000 patients and more than 65 million doses have been distributed to date.

 

And this from the EMA.

 

Investigation into reports of serious adverse events following use of Fluad

EU regulatory authorities following up on suspension of two batches of flu vaccine in Italy

The European Medicines Agency (EMA) is working with the Italian medicines agency (AIFA) and other EU medicines regulatory authorities to investigate the cause of serious adverse events, including deaths, in a small number of elderly patients who had received Fluad flu vaccine. There is so far no evidence to suggest a causal link between the vaccine and the reported adverse events. The suspension is a precautionary measure.

AIFA has suspended the use of two batches of the flu vaccine produced by Novartis. Testing of the batches is underway, as well as a detailed analysis of the case reports from Italy. This includes examining all available information on the affected patients’ age, health condition and medication regime.

The issue will be discussed by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), a scientific body that brings together Europe’s best experts on the safety of medicines, at their meeting starting on Monday, 1 December 2014.

Member States across the European Union continue with their annual flu vaccination campaigns as influenza can cause severe illness or death especially in the elderly and in people with long-term conditions. The World Health Organisation (WHO) estimates that annual influenza epidemics result in about 3 to 5 million cases of severe illness worldwide, and about 250,000 to 500,000 deaths. Influenza vaccines are the most effective way to prevent the disease and/or the serious complications it can cause.

Fluad is authorised in the EU in a number of EU Member States. For the current vaccination campaign, 4 million doses of Fluad have been distributed in Italy. In the EU, the vaccine has also been distributed for the 2014-15 flu vaccination campaign in Austria, Germany and Spain.

NPM14: Giving Preparedness A Shot In The Arm

Photo Credit PHIL

 

Note: September is National Preparedness Month, and this is one of a series of new or updated preparedness articles I will be running for the occasion.

 

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While it is hard to quantify the absolute risks from any of them, in the nearly 9 years that I’ve been doing this blog, I don’t ever recall seeing as many infectious disease threats on the horizon as I do this fall and winter. 

 

In addition to the standard onslaught of seasonal flu (which can vary greatly in intensity each year) and our usual host of winter respiratory viruses (RSV, Adenoviruses, Rhinoviruses), we’ve got a rogue enterovirus sweeping across the nation called EV-D68, affecting mostly (but not solely) kids (see CDC EV-D68 Update & FAQ).

.

 

Another cause of `flu like’ symptoms, but less common than the winter respiratory viruses, are infection via one the vector borne diseases like West Nile Virus, Dengue and Chikungunya. 

What all of these have in common is that they can initially present as do most viral infections  – like a mild cold or the flu; Fever, malaise, body aches . . . sometimes accompanied by a cough or other respiratory symptoms.

All of which not only makes getting a firm diagnosis from your doctor (other than you’ve picked up `a virus’ ) problematic, it increases your chances of picking up `something’. 

 

Much, much further down the list of things to be worried about (at least in North America) are imported exotics like H7N9, H5N1, and MERS-CoV. 

 

Still, they cannot be ruled out completely, as 2 of the 3 have already happened this year (see CDC Statement On 1st H5N1 Case In North America & CDC : 2nd Imported MERS Case Confirmed In Florida), and public health officials continue to watch for additional cases.

 

With heightened scrutiny over these imported threats (not to mention Ebola), traveling while symptomatic (fever, cough, vomiting) may prove exceedingly difficult this fall.  Many international airports are screening passengers for fever, and showing up at the terminal with `flu-like symptoms’  just might get you bumped from your flight . . . or worse.

 

Making this year – perhaps more than ever before – a good year to go ahead and get that flu shot early.  

 

No, the shot won’t protect against any of these exotics.. The vaccine only offers protection against 3 or 4 pre-selected stains of seasonal influenza. Sill, flu is a relatively common severe winter respiratory virus – and claims tens of thousands of lives every year – making it well worth avoiding if at all possible.  

 

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 with immune problems.

 

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.

While the elderly generally see less protection from the flu vaccine, they state that older individuals may still mount a robust immune response. Even if the vaccine doesn’t always prevent infection in the elderly, studies suggest that the vaccine may blunt the seriousness of the illness in those over 65.

 

You might not have thought about it, but 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.

 

Which is why I’ve already paid a visit to my local CVS pharmacy and got my yearly seasonal flu shot.  The process (and the shot – nice job, Carol) were painless.

 

According to the CDC, more than 50 million doses of this year’s flu vaccine have already been distributed, so finding a shot should be no trouble.

 

 

September might seem a little early to be getting the flu shot, but we are already seeing scattered reports of influenza around the country, and it takes a couple of weeks after getting the shot for immunity to kick in. 

 

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.

 

Ready.gov urges all Americans to follow these 3 steps to better preparedness:

GET A KIT

MAKE A PLAN

BE INFORMED

Sage advice. But if you want to be truly prepared, I would add an important 4th step.

Get a shot

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.

(Continue . . . )

 

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.

 

WHO: Recommended Composition Of 2014-15 Northern Hemisphere Flu Vaccine

Credit NIAID

 

# 8314

 

Twice each year influenza experts gather to discuss recent developments in human and animal influenza viruses around the world, and to decide on the composition of the next influenza season’s flu vaccine. Due to the time it takes to manufacture and distribute a vaccine, decisions on which strains to include must be made six months in advance.

 

Which means the composition of the northern hemisphere’s vaccine must be decided upon in February of each year, while decisions on the southern hemisphere’ vaccine are made in September.

 

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. 

 

Of course, there is always the danger that during the manufacturing or service period for this vaccine a new flu virus could emerge (as happened with pH1N1 in 2009), or that one of the currently circulating viruses changes enough antigenically to evade the vaccine. A year is a long time to prognosticate the behavior of influenza.

Yet despite these challenges, most years the flu vaccine turns out to provide at least a moderate level of protection (see CDC Vaccine Effectiveness - How Well Does the Flu Vaccine Work?), and along with good flu hygiene (washing hands, covering coughs, etc.), are your best protection against catching the flu.

 

This week the World Health Organization brought together representatives from  GISRS (Global Influenza Surveillance and Response System), along with members of OFFLU (the OIE/FAO Network on Animal Influenza), and other experts  to determine the recommended composition of influenza virus vaccines for use in the 2014-15 northern hemisphere influenza season.

 

After reviewing copious influenza surveillance reports, the committee has recommended keeping the same formulation as was adopted last February for the 2013-14 flu season, and for the upcoming 2014 Southern Hemisphere flu season (see WHO: Southern Hemisphere 2014 Flu Vaccine Composition).

 

Recommended composition of influenza virus vaccines for use in the 2014-15 northern hemisphere influenza season

20 February 2014

It is recommended that trivalent vaccines for use in the 2014-15 influenza season (northern hemisphere winter) contain the following:

• an A/California/7/2009 (H1N1)pdm09-like virus;
• an A/Texas/50/2012 (H3N2)-like virus;
• a B/Massachusetts/2/2012-like virus.

It is recommended that quadrivalent vaccines containing two influenza B viruses contain the above three viruses and a B/Brisbane/60/2008-like virus.

For more information

Recommended composition of influenza virus vaccines for use in the 2014-15 influenza season - full report
pdf, 166kb

Questions and answers
pdf, 60kb