mBio: Ebola Virus Transmission (What We Know, What We Don’t)

Credit CDC PHIL

 

# 9729

 

The open access journal mBio has published an impressively detailed look at what we know about the transmission of the Ebola virus, penned by lead author Michael Osterholm of CIDRAP (along with an impressive international array of co-authors), that also asks a number of questions regarding what is not known about the virus.

 

Labeled as both an `Opinion’ piece, and a `Hypothesis’, this article also questions some of the assumptions about the behavior of the Ebola virus as it exists today, and as it might exist in the future.

 

Near the end of this paper you’ll find a clearly marked: RESPIRATORY TRANSMISSION OF EBOLA VIRUSES: A HYPOTHESIS, which asks the question:

 

Despite the lack of supportive epidemiological data, a key additional question to ask is whether primary pulmonary infections and respiratory transmission of Ebola viruses could be a potential scenario for the future.

 

Based on some twitter comments this morning, the inclusion of this hypothesis seems to have ruffled some academic feathers. Not being a virologist (or scientist of any stripe), I can’t really speak to the merits of their hypothesis, other than to say:

 

The path to new discoveries often lies in the willingness to continue to ask those questions that others already consider asked and answered.  

 

Whether you agree with their hypothesis (which they call `improbable’, but not impossible) or not, this review is well worth reading, and considering, in its entirety.  

 

Transmission of Ebola Viruses: What We Know and What We Do Not Know

Michael T. Osterholm^a, Kristine A. Moore^a, Nicholas S. Kelley^a, Lisa M. Brosseau^b, Gary Wong^c, Frederick A. Murphy^d, Clarence J. Peters^d, James W. LeDuc^d, Phillip K. Russell^e, Michel Van Herp^f, Jimmy Kapetshi^g, Jean-Jacques T. Muyembe^g, Benoit Kebela Ilunga^h, James E. Strong^c, Allen Grolla^c, Anja Wolz^f, Brima Kargboⁱ, David K. Kargboⁱ, Pierre Formenty^j, David Avram Sanders^k, Gary P. Kobinger^c

 

1. ABSTRACT

Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that “superspreading events” may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013–2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.

(Continue . . . )

Osterholm: What We’re Afraid to Say About Ebola

Credit CDC PHIL

 

# 9067

 

Epidemiologist and CIDRAP director Michael Osterholm, in an editorial that appeared last night in the New York Times, outlines two possible scenarios that `should keep us up at night’  in West Africa’s Ebola outbreak, should it not be brought under control soon.  Helen Branswell also published an interview this morning with Osterholm.

 

• The first is that the Ebola virus spreads from West Africa to other developing nations, and begins to spread in megacities like Lagos, Nairobi, or even Mexico City or Karachi.
• The second, even more ominous scenario, would see the virus mutate into an airborne pathogen, and begin spreading like an influenza pandemic around the world.

While Ebola has remained relatively stable over the nearly 40 years it has been studied, outbreaks in humans have been limited, and long chains of infections have been rare.  With this current outbreak, the virus is getting  unprecedented practice in adapting to the human host as it spread from human-to-human-to human. 

 

What adaptive changes might arise from this prolonged and unprecedented serial passage experiment are impossible to predict, but the potential exists for something to emerge we really, really don’t want to see.

 

This is a possibility we broached a couple of weeks ago in Study: Ebola Virus Is Rapidly Evolving, and was also briefly mentioned by CDC Director Dr. Thomas Frieden last week in a CDC Press Briefing On Ebola. 

 

It was also alluded to in yesterday’s Eurosurveillance Journal editorial (see Stopping Ebola & R0 Calculations) and in Tom Clarke’s blog (see Conventional Wisdom And Epidemic Disease Spread) featuring Professor John Edmunds.

 

First a link to the NYTs piece, then Helen’s interview.  Both are well worth reading in their entirety.

 

What We’re Afraid to Say About Ebola

By MICHAEL T. OSTERHOLMSEPT. 11, 2014

THE Ebola epidemic in West Africa has the potential to alter history as much as any plague has ever done.

There have been more than 4,300 cases and 2,300 deaths over the past six months. Last week, the World Health Organization warned that, by early October, there may be thousands of new cases per week in Liberia, Sierra Leone, Guinea and Nigeria. What is not getting said publicly, despite briefings and discussions in the inner circles of the world’s public health agencies, is that we are in totally uncharted waters and that Mother Nature is the only force in charge of the crisis at this time.

There are two possible future chapters to this story that should keep us up at night.

(Continue. . . )

 

 

September 12, 2014 Updated : September 12, 2014 | 6:24 am

Where is Ebola outbreak going? Nowhere good

By Helen Branswell The Canadian Press

TORONTO – The unprecedented spread of the Ebola virus in West Africa may be pushing the world towards a viral disaster, a commentary published in Friday’s New York Times suggests.

The article reveals that experts are worried ongoing transmission of the virus through people runs the risk of giving rise to mutations that will allow Ebola to spread through the air, like some of the world’s most contagious viruses. The virus currently spreads via contact with contaminated bodily fluids.

(Continue . . . )

MERS: Osterholm On NPR Shots & The Nightly CIDRAP Recap

 

# 8510

 

 

With news of the MERS virus coming at us from multiple countries, and often in piecemeal fashion, it is easy to be overwhelmed trying to divine the signal from the noise.  I know by the end of the day, I’ve become punchy, and I suspect that feeling is shared by my fellow flublogians.

Luckily we get a terrific recap of the day’s MERS developments via CIDRAP NEWS, which usually hits their site around 7pm EDT.

At the end of the day, I confess I often read it just to figure out just what the heck I’ve been blogging about over over the previous 24 hours. A highly recommended nightcap, whose latest example can be found at:

 

Saudi Arabia sacks health chief as MERS cases surge

Robert Roos | News Editor | CIDRAP News |

Apr 21, 2014

The Saudi MERS count surged by 37 cases and 6 deaths in 3 days, including 21 new cases in Jeddah's outbreak.

(continue . . . )

And speaking of CIDRAP, Director Michael Osterholm gives his thoughts to NPR’s SHOTS blog on the recent spike in MERS cases.

Sharp Rise In MERS Cases May Mean The Virus Is Evolving

by

April 21, 2014 7:38 PM ET

There's growing concern that the Middle East Respiratory Syndrome may have entered a new phase in the way it's spreading in Saudi Arabia.

(continue . . )

Osterholm & Mackay On MERS

Coronavirus – Credit CDC PHIL

 

# 8489

 

Epidemiologist Michael Osterholm – Director of CIDRAP and Professor Ian Mackay – Virologist at the University of Queensland (and editor of VDU blog) are two of the smartest people I know when it comes to emerging infectious diseases. 

 

Today both voiced their concerns to AP reporter Adam Schreck, who penned a report on the growing MERS outbreak in the Middle East.

 

You’ll find a link, and the opening paragraph below. Follow the link to read about what Mike calls `a stay tuned moment’ in the ongoing epidemiological investigation.

 

Spate of Mideast Virus Infections Raises Concerns

DUBAI, United Arab Emirates April 17, 2014 (AP)

By ADAM SCHRECK Associated Press

A recent spate of infections from a frequently deadly Middle East virus is raising new worries about efforts to contain the illness, with infectious disease experts urging greater vigilance in combatting its spread.

 

More than 20 people, many of them health-care workers, have been reported infected with the Middle East respiratory syndrome coronavirus in two distinct clusters — one in Saudi Arabia and the United Arab Emirates — likely involving human-to-human transmission since early last week.

(Continue . . .)

Osterholm & Quammen: On The Next Contagion/Pandemic

 

 

# 7257

 

 

Although Crof mentioned them both overnight, Mike Osterholm (Director of CIDRAP) and author David Quammen (see EID Book Review - Spillover: Animal Infections and the Next Human Pandemic) have each penned an op-ed piece for the International edition of the New York Times, and both deserve a second mention here.

 

Both pieces are highly recommended.

 

Rather than try to pick and choose excerpts, I’ll simply post the links and encourage you to follow them.

 

 

The Next Contagion: Closer Than You Think

By MICHAEL T. OSTERHOLM        Published: May 9, 2013 

The Next Pandemic: Not if, but When

By DAVID QUAMMEN     Published: May 9, 2013

 

 

And in case anyone has not yet read it, David’s 2012 book Spillover: Animal Infections and the Next Human Pandemic is an absolutely riveting inside look at the zoonotic pathogens that keep researchers and public health officials up at night.

Link to book on Amazon (excerpts available online)

JAMA: Challenges Of Producing An Effective & Timely H7N9 Vaccine

 

 

 

# 7256

 

In just about every movie or TV show that features a deadly pandemic outbreak - when all seems about lost - noble lab-weary scientists roll out a last-minute experimental vaccine and save the world.  

 

Cue dramatic music, roll credits.

 

Given the reality of vaccine production and distribution, this is the modern equivalent of having a deity descend from the rafters in the final act of a Greek Play to conveniently dispatch any unsolvable problems; a Deus ex Machina (Latin: "god from the machine").

 

As we’ve discussed before, the logistics of producing and deploying a pandemic vaccine in sufficient quantity, and in time to have a major effect on an outbreak, are enormous (see H7N9 Vaccine Realities).

 

And as we learn from an analysis that appears in JAMA today - penned by  CIDRAP’s  Michael T. Osterholm, PhD, MPH; Katie S. Ballering, PhD; and Nicholas S. Kelley, PhD – the obstacles facing the production of an H7N9 vaccine are likely to be even greater still.

 

Rather than try to pick and choose excerpts, I would invite you to follow the link and read:

 

Major Challenges in Providing an Effective and Timely Pandemic Vaccine for Influenza A(H7N9)

Michael T. Osterholm, PhD, MPH; Katie S. Ballering, PhD; Nicholas S. Kelley, PhD

JAMA. 2013;():1-2. doi:10.1001/jama.2013.6589.

Published online May 9, 2013

The emergence of avian influenza A(H7N9) virus in humans has public health authorities around the world on high alert for the potential development of a human influenza pandemic. As of May 8, 2013, authorities had identified 131 confirmed cases and 32 deaths among residents of 8 provinces and 2 municipalities in China.

 

Three primary scenarios exist for how this A(H7N9) virus outbreak will unfold. First, the virus could disappear in the animal reservoir, ending new human cases. Second, the virus could persist in the animal reservoir, resulting in sporadic human infections. Third, the virus could, through mutation or reassortment, become readily transmissible between humans, resulting in a global pandemic.

 

(Continue . . .)

 

UPDATE: Just after I posted this blog, I discovered that Helen Branswell had published a long, and highly informative story that looks at this study, and Canada’s plans regarding vaccine testing.

 

Canada not planning H7N9 bird flu vaccine studies; will watch US results: PHAC

By: Helen Branswell, The Canadian Press

 

 

And for more on the challenges of vaccine effectiveness and production, you may wish to revisit this blog from last November:

 

CIDRAP: The Need For `Game Changing’ Flu Vaccines

Webby On H7N9: `Clear Evidence Of Mammalian Adaptation’

 

Site of recent H7N9 infections

 

# 7059

 

 

Helen Branswell has an important report overnight which includes comments from world renown influenza researcher Richard J. Webby, CIDRAP director Michael T. Osterholm, Gregory Hartl of the World Health Organization, and   Dr. Barbara Raymond, director for pandemic preparedness at PHAC.

 

Dr. Richard Webby -  who became director of the World Health Organization’s Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds at St. Jude Children’s Hospital in Memphis, Tennessee in 2008 - has been highlighted often in this blog.

 

A few recent examples include:

1. Dr. Richard Webby Lecture: Emerging Flu Viruses In The Animal World

2. PLoS Pathogens: A New Influenza C Virus Detected In Swine

3. Egypt: A Paltry Poultry Vaccine

4. PNAS: Virulence & Transmissibility Of H1N2 Influenza Virus In Ferrets

5. Interspecies Transmission Of Canine H3N2 In The Laboratory

 

Webby sees worrying signs of adaptation of the H7N9 virus to mammals – an indication that the virus may now be hosted by non-avian species – like pigs, or humans.

 

Since no one does a flu report better than Helen, at this point I will wisely step aside and invite you to read:

 

New flu virus in China shows signs it has adapted to mammals: Will it take off?

By: Helen Branswell, The Canadian Press

Referral: Reuters - Sleuthing NCoV

 

 

Photo Credit NIAID

 

# 6972

 

The novel coronavirus (NCoV) that has been confirmed in more than a dozen individuals with epidemiological links to the Middle East remains an enigma, with questions regarding its origin, prevalence, and mode of transmission largely unanswered.

 

Today Reuters has an excellent analysis featuring Michael Osterholm (Director of CIDRAP), Mike Skinner (from Imperial College London), flu virologist Wendy Barclay (also at Imperial College London),  Professor of Virology Ian Jones (from Britain's University of Reading), and Volker Thiel (of the Institute of Immunobiology at Kantonal Hospital in Switzerland) discussing their various concerns regarding this emerging pathogen.

 

Follow the link to read:

 

Analysis - Emerging deadly virus demands swift sleuth work

By Kate Kelland, Health and Science Correspondent

LONDON | Wed Feb 27, 2013 1:23pm GMT

 

 

A small sampling of recent blogs on this topic include:

 

Eurosurveillance: Contact Investigation Of NCoV Case Hospitalized In Germany

 

WHO Update on Novel Coronavirus (NCoV)

 

ECDC Updated Risk Assessment On NCoV

Peter Sandman On the CCIVI Vaccine Report

 

# 6638

 

Two days ago Michael Osterholm and his group at CIDRAP released their 160-page Comprehensive Influenza Vaccine Initiative (CCIVI) report, that among other things, cited longstanding overstatement of the effectiveness of the seasonal flu vaccine as a barrier to creating new, and more efficient vaccine technology.

 

Up until about a year ago the CDC’s mantra has been for healthy adults under the age of 65, in years when the vaccine is a good match to circulating strains, effectiveness ranges from 70%-90%.

 

A statement that at times was interpreted as `up to 90% effective’  by officials and the media. A quick Google this morning found the following statement on a major company’s website (link) from 2006.

 

Get a seasonal flu shot every year. The Centers for Disease Control and Prevention (CDC) report that getting a seasonal flu shot the best way to prevent the seasonal flu. In fact it's up to 90% effective in preventing the seasonal flu and even if you catch the seasonal flu, the immunity provided by the vaccine can make your case milder.

 

Not only does this site overstate the effectiveness of the seasonal flu jab, it fails to mention the CDC’s  disclaimer of `in healthy adults under the age of 65’. I can find plenty of instances of this 90% effectiveness meme being used, some as recently as August of this year (link)

 

A little more than a year ago the CDC updated their FAQ on Flu Vaccine effectiveness, and as part of a much longer detailed posting, lowered their estimate of the inactivated flu shot’s effectiveness to read:

 

. . . recent RCTs of inactivated influenza vaccine among adults under 65 years of age have estimated 50-70% vaccine efficacy during seasons in which the vaccines' influenza A components were well matched to circulating influenza A viruses.

 

A number that pretty much matched CIDRAP’s finding (see A Comprehensive Flu Vaccine Effectiveness Meta-Analysis) which would be released a couple of weeks later. That analysis showed the trivalent inactivated vaccine (TIV) had a combined efficacy of 59% among healthy adults (aged 18–65 years).

 

While these numbers are much lower than we would would like to see, 50%-60% protection is far superior to no protection at all.

 

Which is why I continue to get, and support getting, the seasonal flu vaccine.

 

All of which serves as prelude to some extended comments released yesterday by Dr. Peter Sandman on the CCIVI report and public health’s long-standing inclination to overstate the effectiveness of the flu vaccine.

 

For those unfamiliar with Dr. Sandman, he is a world renown expert on crisis communications, who along with his wife and colleague Dr. Jody Lanard, provide consulting services to individuals, organizations, and companies – often during their worst public relations nightmares.

 

Together they also produce a wealth of invaluable risk management advice on their website, which quite frankly should be second home for anyone involved in public relations or risk communications.

 

In the interests of full disclosure Dr. Sandman served on the CCIVI Expert Advisory Group and has worked with CIDRAP in various capacities in the past, points that he makes abundantly clear in his preface. 

 

What follows are excerpts from a lengthy email he sent to Lisa Schnirring of CIDRAP NEWS, in advance of the report’s release, for use in her news articles.

There is so much good content here, I find it difficult to pick and choose excerpts.  As you’ll see, from the title onward, Dr. Sandman does not mince words - so please - follow the link to read it in its entirety.

 

 

We’d Be Likelier to Develop a Better Flu Vaccine If Public Health Officials Didn’t Keep Misleading Everyone about the Flu Vaccine We Have

 

by Peter M. Sandman

(an October 14, 2012 email to Lisa Schnirring of CIDRAP News)

On October 15, 2012, CCIVI released its report, entitled “The Compelling Need for Game-Changing Influenza Vaccines.” The report argued that the current flu vaccine is sorely inadequate; that a key barrier to developing a better vaccine is the widespread judgment that the current one is fine; and that the main reason the vaccine’s effectiveness is so consistently overestimated is that public health officials keep saying it is better than it is.

<SNIP>

Chapter 7 does a fine job of documenting how public health – especially ACIP – overestimates and overstates the efficacy of the flu vaccine. There are really three criticisms here:

• ACIP recommendations for ever-wider flu vaccination have been grounded in claims, assumptions, and judgments that the vaccine was more effective than it actually is.
• Early on that was because good data weren’t available, but long after there were ever-better data showing that the flu vaccine wasn’t very effective, ACIP continued to speak and act as if it were – ignoring some studies, misinterpreting others, leaning too heavily on studies with big methodological flaws, relying on plausibility and expert judgment while claiming to be relying on sound science, etc.
• In their zeal to encourage vaccination, ACIP, CDC, and the rest of the public health leadership kept telling the public (often via state and local public health officials and people’s personal doctors) that the flu vaccine worked better than it works.

<SNIP>

2. How do you think the report will be received? (Some of Chapter 7 sure reads like a GAO report. Lots of investigation work went into the analysis of ACIP’s recommendations.) What areas might see some early impact from the findings?

The central claim in the report is of course its claim that the flu vaccine is a lot less effective than most vaccines and a better one is badly needed.

 

Many in public health will find that claim difficult to embrace. But however reluctantly, I think they will embrace it. The Lancet I.D. study paved the way; in anticipation of that study’s publication, CDC stopped claiming 70–90% effectiveness in healthy adults under 65 and retreated to the much more supportable 50–70% estimate.

 

Now, sadly, CDC and many lower-level public health officials often provide no flu vaccine effectiveness estimate at all in their public communications, having learned that 70–90% is scientifically unsound but fearful that the more accurate 50–70% might undermine public acceptance. This is a small example of officials not trusting the public, which is a very large risk communication problem in public health. (See “Trust the Public with More of the Truth: What I Learned in 40 Years in Risk Communication.”)

 

(Continue . . .)

 

 

The CCIVI report and Dr. Sandman’s comments will undoubtedly discomfit many in the public health field, even if they privately accept their findings. 

 

There is, after all, legitimate concern that anti-vaccine activists will use this report as fodder for their propaganda machine.

 

But in reality, public health faces an even bigger challenge.

 

As I wrote earlier this year in in Science At The Crossroads, the public’s faith in science and technology is eroding. And during a public health emergency, that could prove disastrous.

 

One only has to look at the deep divisions over climate change, evolution, vaccine safety, nuclear power, and genetically modified food crops to realize just how wide this rift between the public and scientists has become.

 

Recent revelations regarding deceit and fraud in scientific research (see PNAS study Misconduct accounts for the majority of retracted scientific publications) have only served to intensify this mistrust.

 

Rekindling the public’s trust is paramount, and the first step in that direction is trusting the public with the truth (or at least, our best estimation of the truth at the time).

 

If the vaccine is only 60% effective, we need to embrace that number and promote it the same way we do seatbelts.

 

Seatbelts don’t guarantee you’ll walk away from a wreck, but they sure improve your odds.

 

Most people understand that, and buckle up.

 

I honestly believe that those who are inclined to get a flu shot will accept those limitations, while those who are vehemently against vaccines  . . .  well, they weren’t going to be persuaded by VE numbers, no matter how high they were.

 

I can’t help but remember what a terrific job the CDC’s Admiral Anne Schuchat - Director of the National Center For immunization and Respiratory Diseases - did during the summer and fall of 2009 briefing the press and the public day after day on the emerging H1N1 pandemic.

 

Her candor, ability to work `off script’ and willingness to concede the things they did not know about the virus were equal parts effective, comforting, and refreshing - and in my mind, anyway – constituted the CDC’s finest hour during that crisis.

 

I believe this type of straight talk should be the model for all public health messaging, even if inconvenient facts (like a VE rate of 60%) are less than comforting.

 

That it is only if you trust the public with the truth that you can win, and hold, their confidence. 

 

Anything less just deepens the rift of public distrust and plays into the hands of the critics.

CIDRAP: The Need For `Game Changing’ Flu Vaccines

# 6636

 

For those of us who promote influenza vaccines as a sensible - and extraordinarily safe (see Harvard Study Reaffirms Safety Of Flu Vaccine) – measure to help prevent the flu each year, there is one caveat we are always obliged to mention.  

 

The flu shot isn’t as nearly as effective as most other vaccines - and in some people (particularly the elderly) - may fail to produce protective levels of antibodies.

 

This is a problem we’ve covered many times before, including:

 

CID Study: Effectiveness Of 2010-11 Flu Vaccine

Study: Flu Vaccines And The Elderly

Flu Shots For The Elderly May Have Limited Benefits

 

 

In October of 2011, in A Comprehensive Flu Vaccine Effectiveness Meta-Analysis, Michael T. Osterholm and his team at CIDRAP produced the largest meta-analysis of influenza vaccine studies to date.

 

A few of their findings for the current flu vaccine:

 

TIV showed efficacy in preventing influenza during 8 of 12 flu seasons (67%) with a combined efficacy of 59% among healthy adults (aged 18–65 years).

 

And among children aged 2-7, the LAIV proved even more protective, showing efficacy in 9 out of 12 flu seasons (75%) with a pooled efficacy of 83%. 

 

The authors concluded that better vaccine technologies are sorely needed as evidence showed influenza vaccine effectiveness to be lower than had been publicly stated in the past. 

 

At best, today’s flu vaccines were shown to provide a moderate level of protection. Certainly better than no vaccination, but quite obviously, not nearly good enough.

 

Osterholm and his team are back today, with a truly impressive 160-page 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.

 

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.

 

 

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

EMBARGOED until 10:00 a.m. CST, October 15, 2012

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.

 

Innovative influenza vaccines currently in investigational research offer the potential of lasting, broad and potent protection against both seasonal and pandemic influenza, but substantial research and policy support is needed to further their development and evaluation.

 

In addition, the report finds that as part of an effort to reduce influenza illness and death, policy shifts toward a universal recommendation for influenza vaccination often were based on professional judgment and not on sound data.

 

The new report, The Compelling Need for Game Changing Influenza Vaccines from the CIDRAP Comprehensive Influenza Vaccine Initiative (CCIVI), follows a review of more than 12,000 peer-reviewed publications, documents, transcripts and notes dating back to 1936 and interviews and follow up with nearly 100 experts in influenza vaccine research, development, and use.

 

“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 . . .)

 

 

There is a natural reluctance for many health care providers to go into great detail regarding the protective value of the flu vaccine.

 

With a vaccine effectiveness rate of under 60%, it’s like trying to sell a bullet-proof vest designed to stop one out of every two bullets. Disclosures like that tend to create market resistance.

 

And so the tendency is to generalize, approximate, or gloss over the effectiveness issue.

 

 

This, Dr. Osterholm believes, creates the false illusion that the current vaccine technology is `good enough’. And that, during a severe pandemic influenza outbreak, could prove disastrous.

 

The study provides 10 key findings.

 

1. During some influenza seasons vaccination offers substantially more protection for most of the population than being unvaccinated; however, influenza vaccine protection is markedly lower than for most routinely recommended vaccines and is suboptimal.

 

2. A major barrier to the development of game-
changing influenza vaccines is the perception that current vaccines are already highly effective in
preventing influenza infection.

 

3. In an effort to reduce influenza morbidity and
mortality, over the last three decades the ACIP
has expanded the populations recommended to
receive influenza vaccine. These recommendations,
however, often were based on professional
judgment and not on scientifically sound data.

 

4. Novel-antigen influenza vaccines in investigational research offer the potential of
lasting, broad, and potent protection; however,
substantial research support is needed to further
develop and evaluate these vaccines.

 

5. The current US government regulatory process for approving influenza vaccines is primarily designed for incremental changes to existing vaccines and presents a barrier to the development of game-changing vaccines.

 

6. Substantial financial risks and inadequate
incentives create significant barriers to bringing
game-changing vaccines to market.

 

7. Coordinated partnerships involving national
governments, the pharmaceutical industry, the
investment community, and academia will be
critical to move such vaccines through clinical
trials and the licensure process.

 

8. Current policy goals for influenza vaccines focus
on increasing production capacity and have not
addressed key public health challenges related to
the effectiveness of current vaccines.

 

9. Significant policy, investment, organizational,
and leadership barriers must be overcome to
achieve novel-antigen game-changing influenza
vaccines.

 

10. Pandemic influenza remains a clear and
compelling threat to our national security and requires commensurate prioritization and an unprecedented coordinated effort among
government, academia, and the private sector to
mitigate this threat.

 

 

Given that this study challenges many long held beliefs, it will be interesting to see how it is received by the vaccine industry, public health officials, and ultimately, the public.

Osterholm: Time To Close The Pig Barns

Credit Wikipedia

 

 

# 6504

 

While the CDC has yet to find evidence of sustained and efficient human-to-human transmission of the emerging H3N2v flu virus, more than 200 human cases reported over the past couple of weeks have made it pretty apparent that this virus jumps readily from pigs to humans.

 

The CDC – citing the lack of H2H transmission and the relative mildness of infections – has advised county fairs and animal exhibits to screen pigs for signs of illness and urge better hygiene among visitors, but has stopped short of recommending the closing of pig barns to the public.

 

Complicating matters, last week we saw a study that showed pigs often carry flu viruses asymptomatically (see EID Journal: Flu In Healthy-Looking Pigs), which makes the advice to identify and isolate sick pigs problematic.

 

This morning, Helen Branswell has a long interview with well known flu expert and CIDRAP  director Michael Osterholm, who believes the time has come to close the pig exhibits at county fairs.

 

Osterholm stresses that we don’t yet know where this virus is going, or how much of a public threat it poses, but that the level of transmission at these venues is sufficient to warrant stronger measures.

 

A link to Helen’s article, then I’ll return with a postscript.

 

August 21, 2012 | 7:00 am

Time to close the pig barns, flu expert says

By Helen Branswell The Canadian Press

TORONTO – It’s been found in pigs and-or people in more than 10 U.S. states and counting. In less than a month, more than 200 people — most young children — have been infected by an unwanted visitor to many of the state and county fairs that are held at this time of year.

 

A new swine flu virus is infecting a growing number of people in the United States. But the official response to this outbreak is substantially different from the one that greeted the swine H1N1 virus that emerged in 2009.

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As I’ve pointed out before, every time this virus jumps from a pig to a human it gets another chance to better adapt to human physiology. Given enough chances, it could evolve into a greater public health threat.

 

So far, we’ve been lucky enough not to have seen a child’s death, or serious illness from this virus.

 

But when we do, you can be sure some aspects of the media a will have a field day excoriating the county fair, local officials, and health department that `let it happen’.

 

Admittedly, the suggestion to close the pig exhibits to the public will not be popular in the farm belt, or among pork producers (who have gone to great lengths to distance themselves from any connection to `swine flu’).

 

But whether the industry likes to admit it or not, pigs are highly susceptible to the influenza virus - and can even serve as `mixing vessels’ - allowing viruses to reassort into new hybrid strains.

 

 

 

The pandemic virus that emerged in the spring of 2009 was the end product of several influenza strains that had kicked around the world’s swine population for many years, trading bits of genetic material back and forth, until they produced a version capable of jumping to humans.

 

The H3N2v virus is likewise a reassortant virus; swine H3N2 combined with the M (matrix) gene from the 2009 H1N1 virus. While the odds of seeing a pandemic emerge from this H3N2v virus appear low right now, they are not zero. 

 

Whatever negative publicity the pork industry might suffer from temporarily shuttering pig exhibits would pale in comparison to the backlash they would see should another swine-origin flu virus take off in a big way in the human population.

 

Nevertheless, the proposal to shutter pig barns is bound to be a sensitive one. It is going to be interesting to see how public health departments, fair officials, and the pork lobby react to Dr. Osterholm’s suggestion in the coming days. 

 

For more on the flu risks from swine reassortments, I’d heartily recommend Helen Branswell’s terrific piece in SciAm  from late 2010 called Flu Factories.

Flu Factories

The next pandemic virus may be circulating on U.S. pig farms, but health officials are struggling to see past the front gate

By Helen Branswell  | December 27, 2010 |

 

 

And for some of my earlier looks at swine influenza, you may wish to revisit:

 

H3N2v: When Pigs Flu

You Say You Want An Evolution?

The (Swine) Influenza Reassortment Puzzle

ScienceInsider: A Flawed Flu Papers Process?

 

 

# 6283

 

 

The `must read’ for today comes from the pen of CIDRAP director and NSABB  board member Michael Osterholm in a letter to the Associate Director for Science Policy at the NIH where he critiques the NSABB’s recent reversal of their previously unanimous decision to block the full publication of Ron Fouchier’s controversial H5N1 ferret studies.

Of the eighteen members who voted again on the issue, twelve recommended publication while six did not.  Osterholm voted in the minority.

 

Jon Cohen writing for Science’s ScienceInsider provides the background, in his report:

 

 

A Flawed Flu Papers Process?

by Jon Cohen on 13 April 2012, 4:26 PM

 

Last month, one-third of the members of the U.S. National Science Advisory Board for Biosecurity (NSABB) disagreed with the group's recommendation to publish in full two studies that describe how to make the bird flu virus transmissible in mammals. Now one of the six dissenters, influenza epidemiologist Michael Osterholm of the University of Minnesota, Twin Cities, has written a sharp critique of the meeting that led to the decision. In a letter sent yesterday to Amy Patterson, an official at the U.S. National Institutes of Health whose office oversees NSABB, Osterholm charged that the meeting was "designed to produce the outcome that occurred."

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Osterholm’s 7-page letter is available  HERE - and regardless where you stood on the publication of Fouchier’s research - Osterholm calls into serious question many aspects of the NSABB review process that should be of concern to all of us.

Helen Branswell has even more on all of this in her recently updated Canadian Press story:

 

Updated: April 13, 2012 | 6:39 pm

Flu expert slams bird flu panel process

By Helen Branswell The Canadian Press

 

In a world where we can now create `designer’ organisms in the laboratory, the biosecurity issues facing life sciences research are becoming increasingly complex. While the benefits of this kind of work may prove enormous, the risks are not trivial.

 

Despite reassurances from researchers, mistakes, laboratory accidents, and even intentional misuse of these new technologies are always possible.

 

Against this backdrop, public confidence in science and scientists continues to deteriorate (see Science at the Crossroads). Already there is a good deal of public resistance to the use of GM (Genetically Modified) food crops, and bio-engineered organisms, and the anti-vaccine movement continues to thrive.

 

If this type of research is to have a viable future, then it must first engender the public’s trust.

 

And based on their handling of this controversy over the past few months, the scientific community has got a long way to go.

mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

Photo Credit – CDC PHIL

 

 

# 6172

 

As I mentioned yesterday in Science: Peter Palese On The CFR of H5N1, not everyone agrees with his analysis of H5N1 seroprevalence studies, which he believes supports the idea that `millions’ of people have already been infected by the virus, and that the true fatality rate (CFR) is far lower than advertised.

 

Today, a counter argument (an added bonus, this is an open access paper) appears in mBio, authored by CIDRAP director Michael T. Osterholm and Nick Kelley.

 

(Fair disclosure: I’m acquainted with both Mike and Nick, and was invited to be presenter at a CIDRAP pandemic conference back in 2009).

 

The paper is called:

 

Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

Michael T. Osterholm Nicholas S. Kelley

Abstract

Two recently submitted (but as yet unpublished) studies describe success in creating mutant isolates of H5N1 influenza A virus that can be transmitted via the respiratory route between ferrets; concern has been raised regarding human-to-human transmissibility of these or similar laboratory-generated influenza viruses.

 

Furthermore, the potential release of methods used in these studies has engendered a great deal of controversy around publishing potential dual-use data and also has served as a catalyst for debates around the true case-fatality rate of H5N1 influenza and the capability of influenza vaccines and antivirals to impact any future unintentional or intentional release of H5N1 virus.

 

In this report, we review available seroepidemiology data for H5N1 infection and discuss how case-finding strategies may influence the overall case-fatality rate reported by the WHO.

We also provide information supporting the position that if an H5N1 influenza pandemic occurred, available medical countermeasures would have limited impact on the associated morbidity and mortality.

 

I would encourage you to read the entire article, where the authors dissect some of the methods used in existing seroprevalence studies.

 

It is quite a detailed analysis, and worthy of your full consideration.

 

After excluding some of the seroprevalence studies that utilized an extremely low antibody titer threshold (in some studies, set as low as ≥1:10), the author’s conclude that:

 

The available seroepidemiologic data for human H5N1 infection support the current WHO-reported case-fatality rates of 30% to 80%

 

The go on to say that:

 

In fact, if H5N1 virus does become a pandemic virus, the virulence (as measured by the case-fatality rate) could decrease 10- to 20-fold from what is currently documented and the virus would still generate a more severe pandemic than the 1918 pandemic, where the overall case-fatality rate was probably about 2%.

 

Given the global population and the current dynamics of population movement around the world, an H5N1 pandemic, even with a relatively low case-fatality rate, would be a truly catastrophic event.

 

I’ve reproduced their summary below.

 

SUMMARY

In summary, we believe that the debate about the case-fatality rate of H5N1 influenza in humans and the suggested important role of currently available antivirals and vaccines in mitigating an H5N1 pandemic are without merit.

 

Furthermore, we do not believe that continued focus on these issues helps to address how best to manage research involving influenza viruses, such as H5N1, that are transmissible between mammals and have the potential to be highly virulent in humans.

 

Future discussions specific to the current controversy need to resolve critical questions such as how we safely conduct H5N1 virus transmission studies in mammals, how we share critical methods and results with those who have a need to know, and how we ensure that laboratory-generated H5N1 viruses do not escape controlled environments.

 

Resolution of these issues with regard to H5N1 influenza viruses has the potential to serve as a template for similar situations involved existing or emergent pathogens. It is our belief that the current controversy provides a valuable opportunity for scientists and public policy experts to work together in creating this road map for the future.

 

Notes

Dr. Osterholm is a member of the National Science Advisory Board for Biosecurity. His views expressed here do not represent the official policy or scientific conclusions of the NSABB.

 

 

NOTE: Since this was an open access paper I was able to incorporate more of it into today’s blog than I could with yesterday’s Palese paper.

 

 

I suspect this debate will rage, unresolved, until we get more and better data.

 

Hopefully, we’ll get that data from well mounted and standardized seroprevalence studies, and not from the butcher’s bill from the next pandemic.

CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis

 

 

 

# 5924

 

I hadn’t intended today to be a `theme’ day at AFD, but things have certainly turned out that way.  

 

I started early this morning with a study on the reduced immune response from the flu vaccine among the obese (here), and this afternoon posted a link to the on-target comments by Dr. Jody Lanard on the CDC’s recent rollout of vaccine effectiveness numbers (here).

 

For the hat trick I’ve saved the best for last.

 

A comprehensive study lead by Michael T. Osterholm, director of CIDRAP (the Center for Infectious Disease Research and Policy) at the University of Minnesota, that provides a systematic review and meta-analysis on the efficacy and effectiveness of the TIV (trivalent Inactivated Vaccines) and LAIV (Live attenuated influenza vaccine) influenza vaccines.

 

Note: Most of the time, the terms `effectiveness’ and `efficacy’ can be used interchangeably, but in the scientific world there are subtle differences.

 

Effectiveness describes how well something works under day-to-day, real-world conditions.  In the following study, it is used to gauge the results of observational studies.

 

Efficacy describes how well something performs in a more controlled setting – and here it is used to describe the results of randomized placebo-controlled clinical trials.

 

Researchers at CIDRAP, along with colleagues from  the Marshfield Clinic Research Foundation and Johns Hopkins University examined more than 5700 existing  vaccine studies going back to 1967, and found 31 that met their (admittedly strict) criteria for inclusion.

 

What they were looking for were well-mounted studies that used highly sensitive laboratory testing (RT-PCR or culture) to confirm influenza infection in its participants.

 

Since the flu vaccine cannot be reasonably be expected to protect against non-influenza respiratory illness (ie. rhinovirus, adenovirus, enteroviruses, etc.), studies that fail to do this sort testing are of considerably less value.

 

 

 

After an exhaustive examination and whittling down process, fewer than 3 dozen studies met their criteria. As a result there remain some significant gaps in the evidence.

 

For example, there were no randomized controlled trials (RTCs) showing efficacy of the TIV (trivalent Inactivated Vaccines) in those aged 2–17 years or in adults 65 years or older. 

 

Similarly, they found no RCTs showing the efficacy of the LAIV (Live attenuated influenza vaccine) for people aged 8–59 years.

 

 

In the discussion, the authors write:

 

The evidence from trials and observational studies suggests that presently available influenza vaccines can provide moderate overall protection against infection and illness, with LAIV providing a consistently higher level of protection in children aged 7 years or younger.

 

But they found the protective effects of the flu vaccine could vary considerably from one season to the next, and among different age groups. Some years, and in some cohorts, there was little evidence of protection.

 

Although some of the numbers are lower than have been commonly stated in the past, today’s flu vaccines were shown to provide a moderate level of protection. 

 

TIV showed efficacy in preventing influenza during 8 of 12  flu seasons (67%) with a combined efficacy of 59% among healthy adults (aged 18–65 years).

 

And among children aged 2-7, the LAIV proved even more protective, showing efficacy in 9 out of 12 flu seasons (75%) with a pooled efficacy of 83%. 

 

 

Beyond the numbers, which probably represent the most accurate assessment of influenza vaccine effectiveness to date, this study also highlights the folly of depending upon a vaccine technology that has changed little since the 1950s.

 

Not only does it take too long to produce an emergency vaccine in the face of a pandemic . . .  those at greatest risk from a novel influenza virus are likely to receive the least amount of benefit from today’s vaccines.

 

The study’s authors say their findings should be seen as a clarion call for the development of more effective influenza vaccines.

 

Until that can happen, and despite these lower efficacy numbers, they still recommend getting the seasonal flu vaccine.     

 

Robert Roos, News Editor for CIDRAP (which operates independently of CIDRAP’s  research and policy programs) provides a good deal more detail on all of this, including extensive remarks by Dr. Osterholm.

 

 

Strict meta-analysis raises questions about flu vaccine efficacy

Robert Roos  News Editor

Oct 25, 2011 (CIDRAP News) – A rigorous new analysis of 44 years' worth of studies is raising questions about the evidence for the effectiveness of influenza vaccines in elderly people and, for certain types of vaccines, in children and younger adults as well.

 

Applying very strict criteria to filter out potential bias and confounding, a US research team sifted more than 5,000 studies and found only 31 that they felt provided reliable evidence about the efficacy and effectiveness of flu vaccines. The findings were published online today by Lancet Infectious Diseases.

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(Cites)

Osterholm MT, Kelley NS, Sommer A, et al. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2011 (published online Oct 25)

Kelly H, Valenciano M. Estimating the effect of influenza vaccines. (Commentary) Lancet Infect Dis 2011 (published online Oct 25)

Osterholm On The Recent Rise In Bird Flu Reports

 

 

 

# 5354

 

This morning we are still watching a couple of potential human H5N1 `clusters’ in Indonesia, although neither has been confirmed by laboratory testing as yet. 

 

In one, 5 infants in the city of Padang are hospitalized (up from 2 yesterday) and in another, a family of 4 in Indramayu are in isolation (see More Indonesian Bird Flu Suspicions).

 

 

Despite difficulties getting timely news out of Egypt due to the political upheaval, we are aware of at least 6 human H5N1 infections in the first two months of the year and there may be others. 

 

And we’ve seen three human cases in Cambodia over the past 30 days as well.

 

And from Korea to Japan, and from India to Bangladesh, and of course in Indonesia and Egypt, outbreaks in poultry and wild birds are continually being reported.

 

Bird flu, it would seem, is back in a big way.

 

If you are a reporter anywhere in the Minneapolis area (or the nation, for that matter), and are looking for an expert comment on bird flu, or any other public health issue, the `go to’ person is Michael Osterholm, director of CIDRAP at the University of Minnesota.

 

 

And CBS news does exactly that with the following brief interview with  Dr. Osterholm on the recent rise in bird flu activity.   A short audio interview is available at the link below.

 

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

 

 

Is Bird Flu Making A Comeback?

March 3, 2011 12:34 PM

 By Steve Murphy, NewsRadio 830 WCCO

MINNEAPOLIS (WCCO) — Avian flu claimed 310 lives in 15 countries from 2004 to 2006, then the disease quieted down — until now.

 

“Actually, we’ve had as much activity in the bird side of it — meaning poultry flocks, wild birds and humans — in Asia and Africa over the past four months as we’ve really had at almost any time since H5N1 became a problem back in 2004,” said noted University of Minnesota disease expert Michael Osterholm.

 

Osterholm says the increased activity “has really got us concerned.”

CIDRAP Reports On Cell Based Vaccine Trial

 

 

# 4965

 

Last night Robert Roos, news editor for CIDRAP, wrote a long and informative article on the results of a new study on cell-based vaccine production.

 

As an added bonus, you’ll find extended and insightful comments from CIDRAP’s director, Dr. Michael Osterholm.

 

Although hailed by proponents as the future of vaccine production, cell-based vaccines still have obstacles ahead. And as Dr. Osterholm points out, cell-based vaccine production may provide only an incremental improvement over egg-based technology.

 

Follow the link, this report is well worth reading it its entirety.

 

 

Trial answers some, not all, questions on cell-based flu vaccines

Robert Roos News Editor

Oct 6, 2010 (CIDRAP News) – A new report says that a cell culture derived influenza vaccine and a conventional egg-based vaccine both proved effective in a large international clinical trial, offering support for those who contend that cell-based vaccines should become an important part of flu vaccine supplies in coming years.

 

But it remains to be seen whether cell culture production, which has been discussed for years, is the wave of the future for flu vaccines. Some doubts persist as to whether it offers sufficient advantages in effectiveness and production time to replace the traditional egg-based technology.

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UMN’s Osterholm And Kahn On Allegations Against WHO

 

 

# 4639

 

 

CIDRAP’s Director Michael Osterholm and Director of the University of Minnesota’s Center for Bioethics, Jeffrey Kahn respond to a story printed earlier this week by by Susan Perry of MinnPost.com  regarding recent allegations made against the World Health Organization on the handling of the pandemic. 

 

A hat tip to Shiloh on FluTrackers for posting this link.   The entire article is well worth reading.

 

 

U of M's Osterholm and Kahn respond to criticisms of WHO's handling of H1N1 pandemic

By Susan Perry | Published Thu, Jun 10 2010 9:04 am

Talk about opening up a hornets’ nest.

 

As I wrote earlier this week, two new reports — one [PDF] from the Parliamentary Assembly of the Council of Europe and the other in the form of an investigative article in the British Medical Journal (BMJ) — have taken direct aim at the handling of the H1N1 pandemic by the World Health Organization’s (WHO).

 

The most troubling charges in the reports are that WHO let researchers with financial ties to pharmaceutical companies that sell antiviral drugs and influenza vaccines influence its pandemic-related decisions and recommendations.

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Over the past week, since these latest charges were levied, a number of well respected flu scientists have come forward to defend the actions of the WHO.   

 

You’ll find some of those statements in:

 

Experts Weigh In On Allegations Against The WHO

CIDRAP Dissects The WHO Allegations

 

Last January Revere at Effect Measure had a scathing assessment of the leader of the Council of Europe’s Inquisition, Wolfgang Wodarg in Fire in the hole: Wolfgang Wodarg and WHO.

 

You’ll find my own comments on the charges levied by the COE in WHO To Review Their Pandemic Response.