Showing posts with label CFR. Show all posts
Showing posts with label CFR. Show all posts

Revisiting The H5N1 CFR Debate

 

 

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Source – WHO as of 6/7/12

 

 

 


# 6401

 

One of the more contentious aspects of the H5N1 research debate of the past 8 months has been the argument over the `real’ CFR (Case Fatality Ratio) of the H5N1 virus in humans.

 

The `official’ number – a fatality rate of roughly 60% – is derived from the total known human infections by the virus (606 as of June 7th, 2012), and the total number of fatalities within that group (357)

 

Critics point out that only the sickest of the sick would end up in a testing environment, and that many mild cases would recover and never be counted.

 

The numbers, they maintain, are badly skewed.

 

Last February (see Science: Peter Palese On The CFR of H5N1) the journal Science published a meta-analysis by  Taia T. Wang,  Michael K. Parides &  Peter Palese, that argued that we are likely missing a great many H5N1 infections (perhaps millions), and that the virus is far less lethal than has been assumed in the past.

 

That argument was countered by CIDRAP director Michael T. Osterholm and Nick Kelley in an mBio  article, where they found little serological evidence to suggest that we are missing `millions’ of uncounted H5N1 infections (see mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective).

 

Today, we’ve a new response to the Palese meta-analysis appearing in the journal Science. One with a remarkable pedigree; attached you’ll find some of the biggest names in influenza research:

 

 

Comment on “Seroevidence for H5N1 Influenza Infections in Humans: Meta-Analysis”

Science 22 June 2012:
Vol. 336 no. 6088 p. 1506
DOI: 10.1126/science.1221434

Maria D. Van Kerkhove, Steven Riley,Marc Lipsitch, Yi Guan, Arnold S. Monto, Robert G. Webster, Maria Zambon, Angus Nicoll, J. S. Malik Peiris, Neil M. Ferguson

Abstract

A better understanding of the severity of H5N1 in humans is needed. Wang et al. (Brevia, 23 March 2012, p. 1463; published online 23 February 2012) over interpret the results of seroprevalence studies and take too little account of underlying uncertainties. Although the true risk of death from H5N1 infection will likely be lower than the 60% of reported laboratory-confirmed cases, there is little evidence of millions of missed infections.

 

Their entire rationale may be read here, and it strongly counters the assessment presented by Wang et al. in the original paper.

 

Dueling opinion pieces, regardless of the credentials of those involved, can’t really settle this argument. What we need are more, and better, seroprevalence studies in places where the H5N1 virus is endemic to come to any firm conclusions.

 

While most researchers accept that the 60% CFR number is probably far too high, as the authors of today’s article caution, in the absence of compelling data to the contrary:

 

“The precautionary principle dictates that we continue to assume that natural H5N1 infection in humans carries a high risk of death”

 

A policy I would certainly endorse.

»» Read More

Differences In Virulence Between Closely Related H5N1 Strains

 

 

 

# 6286

 

 

One of the difficulties in determining the CFR (Case Fatality Rate) of the H5N1 virus (see The Great CFR Divide) is the fact that at least 20 distinct clades of the virus have so far been identified (with numerous variations among each clade), and that there appear to be differences in how they behave.

 

`Clades’ are essentially branches on the virus’s family tree. Each new branch has a clearly identifiable lineage from its parental strain, but has mutated far enough away to become a new strain.

 

The World Health Organization’s report from October of 2011, Updated unified nomenclature system for the highly pathogenic H5N1 avian influenza viruses, identifies and updates the known clades of the H5N1 virus that have emerged since the detection of the A/goose/Guangdong/1996 H5N1 virus strain back in the mid 1990s.

 

All of which means we are not watching just one H5N1 virus strain with pandemic potential, we are watching at least 20 genetically separate clades of the virus, with many minor variants of each clade thrown in the mix.

 

And over time, it is expected that even more clades will emerge as the virus mutates and/or swaps genetic material with other viruses.

 

To give you an idea of just how much the virus has diversified over the past 15 years, I’ve reproduced one of the WHO charts from in this report below.

 

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(click to load larger image)

 

And among these different clades and strains (some of which have disappeared over the years), there appears to be a significant variation in its virulence, host range, and likely - transmissibility.

 

Anecdotally, a look at the latest World Health Organization tally of known human H5N1 cases shows a wide spread in case fatality rates around the world.

 

The latest global tally of human H5N1 cases from the WHO show 23 confirmed H5N1 infections for 2012, and 14 fatalities.

 

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In Bangladesh, of the 6 known cases, none have died, while in Cambodia 18 or 20 have succumbed to the virus.  In Egypt, the CFR is running about 35%, while in Indonesia, it is nearly 83%.

Although there are likely many factors involved in causing this disparity in CFR – including quality of, and delays in seeking medical care – it suggests that the H5N1 virus is more virulent in some regions of the world than in others.

 

Which brings us to a study that recently appeared in the Journal Transboundary and Emerging Diseases that looked at two very similar H5N1 viruses of the same clade (2.3.2.1) that produced widely varying pathogenicity in mice and ducks.

 

 

Two Highly Pathogenic Avian Influenza H5N1 Viruses of Clade 2.3.2.1 with Similar Genetic Background but with Different Pathogenicity in Mice and Ducks

J. Hu, K. Zhao, X. Liu, X. Wang, Z. Chen, X. Liu

Article first published online: 12 APR 2012

DOI: 10.1111/j.1865-1682.2012.01325.x

Summary

A number of genetic markers for virulence of avian influenza viruses (AIVs) in different hosts have been identified. However, we isolated two H5N1 AIVs, A/Chicken/Jiangsu/k0402/2010(CK/10) and A/Goose/Jiangsu/k0403/2010(GS/10) with similar genetic background, but most well-defined molecular markers for virulence in mammals and avian species were not found in both viral genomes.

In addition, pathogenicity of this pair of viruses in different hosts remains unclear. Therefore, we evaluated their pathogenicity in chickens, mice, ducks and guinea pigs. Infection of CK/10 and GS/10 in chickens caused 100% mortality within 24 h.

Mouse experiment showed that CK/10 was highly pathogenic (MLD50 = 0.33 log10 EID50), whereas GS/10 was avirulent (MLD50 > 6.32 log10 EID50).

Interestingly, the virulence of CK/10 in ducks (DLD50 = 3.83 log10 EID50) was higher than that of GS/10 (DLD50 = 7.7 log10 EID50), which correlated with viral pathogenicity in mice. Although CK/10 and GS/10 showed distinct pathogenicity in mice, they both were lethal to guinea pigs, with CK/10 replicating to higher titres in airways than GS/10.

Collectively, these findings suggest that AIVs with similar genetic backgrounds may exhibit distinct pathogenicity in specific hosts and that some unknown molecular markers for virulence may exist and need to be identified.

 

 

With differences this great in the pathogenicity of two closely related H5N1 viruses, one might reasonably assume that even greater differences in host range, transmissibility, and virulence may exist between more dissimilar clades.

 

Which just might help explain the `dueling studies’ problem, where some seroprevalence studies have shown a small but significant percentage of apparent asymptomatic H5N1 infections in exposed populations, while the majority have not.

 

Granted, none of this brings us any closer to knowing  the true CFR of the H5N1. 

 

But that may well be an impossible question to answer accurately, unless we first specify which strain, clade, or sub-clade of the virus we are talking about.

»» Read More

Another Entry Into The H5N1 Lethality Debate

 

 

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# 6215

 

 

With the announcement last fall that two researchers had successfully created a ferret-transmissible (and in one case, lethal), version of the H5N1 virus there have been fresh calls to regulate and restrict just how, and where, this sort of research should be conducted.

 

While not guaranteed - successful adaptation to ferrets (which have respiratory systems similar to humans) is assumed by many researchers to be a pretty good indication it would transmit in humans as well.

 

Suddenly labs that have been working with variants of the H5N1 virus are under new scrutiny, and regulators are questioning just how much biosecurity is needed to work on these viruses.

 

Last month Canada decided to restrict H5N1 research to labs with the highest biosecurity measures (see  Canada Issues Biosafety Advisory For H5N1 Research), and other countries are considering similar measures.

 

In an attempt to assuage fears over the risks of H5N1 research (and the publication of the results), several well respected scientists have challenged the notion that the bird flu virus is as lethal in humans as is commonly portrayed.

 

One high profile paper appeared in Science last month -Seroevidence for H5N1 Influenza Infections in Humans: Meta-analysis - authored by Professor Peter Palese et. al., that argues that we are likely missing a great many uncounted H5N1 infections, and that the virus is far less lethal than has been assumed in the past.

 

This is similar to the argument that Vincent Racaniello offered last January in his blog Should we fear avian H5N1 influenza?

 

While stating that we don’t have definitive numbers, Palese writes that if one assumes a 1-2% infection rate among exposed populations, there would likely be millions of people who have been infected by the H5N1 virus.

 

Palese grants that deaths from the virus may also be undercounted, and calls for better studies (something that I think everyone, regardless of where they stand on this issue, would agree with).

 

A counter argument appeared last month in mBio, authored by CIDRAP director Michael T. Osterholm and Nick Kelley. 

 

They found little evidence to support the notion that we are missing `millions’ of uncounted H5N1 infections (see mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective), and find that the H5N1 virus has the potential to be highly virulent in humans.

 

 

Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

Michael T. Osterholm Nicholas S. Kelley

 

All of which serves as prelude to a new analysis, authored by Eric S. Toner and Amesh A. Adalja (both of the Center for Biosecurity at the University of Pittsburgh Medical Center (UPMC)) published last week in Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science.

 

Is H5N1 Really Highly Lethal?

Eric S. Toner and Amesh A. Adalja.

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science. doi:10.1089/bsp.2012.022

 

I would invite you to read the entire study (it is reasonably short), but an excerpt from the press release sums it up nicely:

 

The authors review the available evidence: the distinctions between different clades of H5N1, the clinical series of human H5N1 cases, and the seroepidemiological and laboratory studies. They conclude that the preponderance of evidence argues that H5N1 virus is indeed highly lethal in humans compared to other influenza viruses.

 

Author Eric Toner said, “Our review of the evidence underscores what so many experts have been saying for years: Wild-type H5N1 is a very dangerous virus. We are quite fortunate it has not yet become contagious between humans.”

 

 

Dueling opinion pieces obviously won’t settle this argument, and regrettably, the amount of hard data available to support either position is limited.

 

While I suspect the virus is less deadly than the `official numbers’ suggest  - given the stakes - it would seem to this humble blogger that if we err, we ought to err in favor of overestimating the threat of this virus.

 

At least in the short run.

 

We can always relax policies later when we have more accurate data and a better handle on the threat. 

 

 

But underestimating this virus now, before we have solid answers, could lead to an irrevocable error.

»» Read More

The Great CFR Divide

 

 

 

# 6173

 

 

Over the past two days we’ve seen two highly divergent papers come out on the probable spread, and Case Fatality Rate, of the H5N1 virus in the human population.

 

The lead author of the first one was Peter Palese and the second Michael Osterholm. Both are scientists of considerable reputation in the world of infectious diseases.

 

You can access them via my blogs below:

 

Science: Peter Palese On The CFR of H5N1
mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

 

In 25 words or less, though:

 

Professor Palese maintains that seroprevalence studies suggest `millions’ of uncounted H5N1 infections, and would indicate the virus is nowhere near as deadly as has been proclaimed.

 

Osterholm cites flaws in some of those studies, and using WHO guidelines for testing, finds scant evidence to support the idea that many cases go uncounted, and the CFR is low.

 

Shamefully simplistic summaries on my part, but we’ve covered this territory many times in the past few days. I would encourage everyone to read both papers in their entirety.

 

In the wake of their publication, we are starting to see some media coverage and comparison of the two papers, and reactions from other scientists on this issue.

 

First stop, Reuters, which has a long report on this controversy, which was published before the mBio  paper was released this morning.

 

Bird flu may not be so deadly after all, new analysis claims

By Sharon Begley

NEW YORK | Fri Feb 24, 2012 6:38am EST

 

Despite the title, this report does quote the World Health Organization as standing behind their numbers, and has comments by Arturo Casadevall and Michael Osterholm disputing Palese’s results.

 

Next, New Scientist has a report by Debora MacKenzie that looks at the debate, and along the way she posits a theory of her own.

 

New doubt over H5N1 death rate – but risks still high

16:50 24 February 2012

 

 

And lastly, Lisa Schnirring of CIDRAP News has undertaken a difficult task and (skillfully, I think) has put together a comparison of the two papers.

 

She includes reactions from several leading scientists (including Gaun Yi and Marc Lipsitch) who have read the papers.

 

 

Debate on H5N1 death rate and missed cases continues

Lisa Schnirring * Staff Writer

Feb 24, 2012 (CIDRAP News) – Two leading voices on the potential threat of lab-modified H5N1 viruses laid out their arguments about the human H5N1 fatality rate and undetected cases today and yesterday, with one group claiming "millions" likely have been infected and the other group saying current World Health Organization (WHO) fatality-rate estimates are about right.

 

(Continue . . . )

 

 

While this is a fascinating debate, and I know just about everyone would like to know the true CFR of the H5N1 virus (myself included), I’m not sure how much value (or comfort) that we would derive if we had that knowledge.

 

First, we tend to talk about the H5N1 virus as if it were a single, monolithic virus.

 

It isn’t.

 

There are more than 20 identified clades (and growing), with many minor variations within each clade.

 

image 

 

If we could figure out the CFR for the clades commonly found in Indonesia (2.1.1, 2.1.2. and 2.1.3), it probably wouldn’t tell us much about those circulating in Egypt (2.2.1 and 2.2).

 

And it might tell us even less about the CFR of some future human-adapted H5N1 virus that may one day appear.

 

As any prospectus will warn you, Past performance is no guarantee of future results.

 

So even if we were accept that Professor Palese is correct, and the CFR of currently circulating H5N1 strains are somewhat less than 1%, I’m not exactly comforted by that knowledge.

 

I think what is important here is that this virus has been shown to provoke severe, often devastating illness in nearly all of the humans cases we’ve confirmed so far. It also seems to have a preference for younger victims.

 

Admittedly, that could change as the virus evolves.

 

But it is enough to convince me that we need to regard this virus as a dangerous and formidable pathogen, regardless of whether its CFR right now turns out to be 30%  or .3% or somewhere in between.

 

Because if a new and improved version of the virus ever emerges, all of the old arguments (and datasets) will quickly become academic.

»» Read More

mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective

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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.

»» Read More

Science: Peter Palese On The CFR of H5N1

 

 



# 6169

 

 

One of the livelier `sideshows’ in the vigorous debate over the safety and wisdom of H5N1 lab research has been the argument over just how deadly the H5N1 virus really is.

 

Although the virus first appeared 15 years ago in Hong Kong that question remains difficult (perhaps, impossible) to answer.

 

The media has reported, ad nauseum, that the virus kills 6 out of 10 people it infects. Which would give it a CFR (Case Fatality Ratio) about 60%.

 

But then it gets complicated.

 

We literally have no good read on how many people the virus has actually infected.  If `mild’ or asymptomatic infections occur, then they are unlikely to be noticed.

 

A large part of the reason is that surveillance is less than robust in many of the regions where the virus is endemic. Testing – when it is done (and often it isn’t) – has long suffered from sensitivity problems. 

 

Beyond that, many people who get sick (and even die) in places like Cambodia, Vietnam, or China may do so without ever seeking medical care.

 

Intuitively we can say that these cases almost certainly exist, but we have no way to accurately measure them. In truth, even the CDC can’t tell you exactly how many people are sickened or die from the flu (or any other cause) each year.

 

Most scientists would grant that what we see with the H5N1 virus is probably the tip of the iceberg. It is the size of what lies beneath that visible tip that is heavily disputed.

 

Today we’ve a paper, authored by Professor Peter Palese  et. al., that argues that we are likely missing a great many uncounted H5N1 infections, and that the virus is far less lethal than has been assumed in the past.

 

This is similar to the argument that Vincent Racaniello  used last month in his blog Should we fear avian H5N1 influenza?

 

The reason behind this debate – beyond the obvious need to quantify an important aspect of this virus – is the debate over whether this virus is too dangerous to work with in a BSL-3 laboratory environment. 

 

Relegating it to the highest containment labs (BSL-4), it has been argued, would severely restrict the number of scientists (and countries) who could work on this pathogen

 

 

One way to get an idea of the uncounted number of people infected by a virus in a population is to conduct regional seroprevalence studies.

 

You essentially check antibody levels against a specific virus in a representative group of the population.

 

Unfortunately, you don’t end up with a clear cut Infected/Not Infected reading from these tests. You get an antibody titer level, and that requires a subjective decision as to what level constitutes proof of a `previous infection’.

 

Set the bar too high, and you rule out possible cases whose antibodies have declined over time (or who were exposed to an antigenically different H5N1 strain).

 

Make it too low, and you may count people who were exposed to a non-H5 virus or who received such a low viral load as to not develop illness or immunity. 

 

Over the years we’ve seen a number of seroprevalence studies on the H5N1 virus, and the results (and methods) have varied considerably.

 

Palese’s paper appears today in the journal Science (the embargo lifts at 2pm EST), and here he makes his case:

 

Seroevidence for H5N1 Influenza Infections in Humans: Meta-analysis


Taia T. Wang,  Michael K. Parides,  Peter Palese

ABSTRACT

The prevalence of avian H5N1 influenza A infections in humans has not been definitively determined. Cases of H5N1 infection in humans confirmed by the World Health Organization (WHO) are fewer than 600 in number with an overall case fatality rate of >50%.

We hypothesize that the stringent criteria for confirmation of a human case of H5N1 by WHO does not account for a majority of infections, but rather, the select few hospitalized cases that are more likely to be severe and result in poor clinical outcome.

Meta-analysis shows that 1-2% of more than 12,500 study participants from 20 studies had seroevidence for prior H5N1 infection.

 

While stating that we don’t have definitive numbers, Palese writes that if one assumes a 1-2% infection rate among exposed populations, there would likely be millions of people who have been infected by the H5N1 virus.

 

Palese grants that deaths from the virus may also be undercounted, and calls for better studies (something that I think everyone, regardless of where they stand on this issue, would agree with).

 

If we assume that Professor Palese is correct in his assumptions, then the H5N1 would seem to be not much more dangerous than some strains of seasonal flu.

 

A comforting thought.

 

But one that seems at odds with the argument proffered by many scientists calling for aggressive research into the H5N1 virus because of its serious `pandemic potential’.

 

Of course not everyone views the available data in quite the same way as does Professor Palese.

 

We’ll be getting a counter-argument either later today or tomorrow from Michael Osterholm and Nick Kelley of CIDRAP, who have their own analysis coming out in mBio this week (see press release).

 

Stay tuned.

»» Read More

CIDRAP: Exploring the CFR Of H5N1

 

 

 

# 6133

 

Since the H5N1 virus reappeared in 2003, the CFR (Case Fatality Rate) of that strain of avian flu has hovered around 60%. Some countries – like Indonesia & Cambodia are well into the 80% fatal range, while Egypt has somewhat lower CFR of about 35%.

 

The 1918 pandemic, by comparison, is believed to have only killed 2.5% of its victims.

 

Over the years a number of researchers have insisted that the true fatality rate must be far lower, and that limited surveillance systems in countries where the virus is endemic are only picking the `sickest of the sick’, who are most apt to die.

 

While long a bone of contention among flu specialists, recently this has become a part of the larger debate over the implied risks of publishing  dual use’ H5N1 research.

 

Robert Roos of CIDRAP takes on this daunting topic today in a lengthy and important article.

 

 

Undetected H5N1 cases seem few, but questions persist

Robert Roos * News Editor

Feb 9, 2012 (CIDRAP News) – The fatality rate for officially confirmed human cases of H5N1 avian influenza infection is a stunningly high 59% (345 deaths in 584 cases). But the current controversy over publishing data about transmissible H5N1 viruses has revived a debate about whether the virus is as lethal as those numbers say.

 

(Continue . . .)

»» Read More

Racaniello On H5N1’s Fatality Rate

 


# 6050

 


Vincent Racaniello, Professor of Microbiology at Columbia University Medical Center and host of 3 weekly podcasts (TWIP, TWIM and TWIV), also pens the outstanding Virology blog.

 

Today he has a post on the supposed CFR (Case Fatality Ratio) of the H5N1 virus. 

 

The mantra in the popular press is that bird flu kills `60% of those infected’. We seen it used a lot over the past month, particularly in cautionary media stories regarding the dangers of bird flu research.

 

It’s a simplistic view, of course, because we don’t know how many mild or even asymptomatic cases occur that are never reported.

 

This is something we’ve discussed often, including last December, in Study: Subclinical H5 & H9 Infections In Humans, where we saw a report out of China on the detection of antibodies to both H9 and H5 avian influenza viruses among a small number of villagers in and around Beijing, China.

 

Similarly, last September we saw a study that reported the results of serological testing conducted in a rural village in Thailand in 2008 (see Bangladesh To Share H9N2 Bird Flu Virus). 

 

Out of 800 villagers tested, the authors found 4.7% were seropositive for the Hong Kong H9N2 avian strain, 5.6% had antibodies to A/Thailand/676/2005 H5N1 bird flu, and 3.5% were shown to be seropositive to A/Thailand/384/2006 H5N1.

 

The implications of these studies are that human infection with these avian viruses – while still pretty rare – probably occur more often than current surveillance and reporting suggests.

 

And if true, that would dilute the 60% CFR number.

 

Perhaps considerably.

 

As Professor Racaniello explains, until we can get a good handle on how many `mild or asymptomatic’ infections occur, we really can’t determine the true fatality rate of the virus.

 

Follow the link below to read:

 

Should we fear avian H5N1 influenza?

3 January 2012

By Vincent Racaniello

influenza virus

»» Read More

The Numbers Disconnect

 

 

# 4147

 


If you accept the CDC estimate that roughly 10,000 Americans have died as a result of the H1N1 related illness (as of mid-November), then you have to seriously question some of the other numbers that are being bandied about globally.

 

The US estimate of 10,000 deaths is about 1 death for every 30,000 people in the country.  

 

  • The UK, on the other hand, is reporting only 138 deaths (population 60 million).    That’s 1 death in every 435,000 people.
  • Japan, with twice the population of the UK, is reporting just 100 deaths. 
  • And China, with 1.3 Billion people, is reporting only 300 deaths.

 

Is the US death rate really 14 times that of the UK?  Or 42 times that of Japan.  Or 144 times greater than China?

 

Not likely.

 

Today, the UK papers are pushing the idea that the Swine flu pandemic is `far less lethal than originally feared’.  

 

And that is true.

 

This has not been a particularly lethal strain of influenza.  But the numbers being used in today’s reportage would appear less than realistic.  

 

This excerpt from The Nursing Times.

 

 

Swine flu 'less lethal than feared'

11 December, 2009

Chief Medical Officer Sir Liam Donaldson claims the swine flu pandemic is ‘considerably less lethal’ than feared, but has warned this should not be an excuse for ‘inaction’.

 

Figures show that the death rate from the disease is lower than 0.1%, with 26 fatalities for every 100,000 cases in England.

 

The research, published online in the journal British Medical Journal analysed data for up to November 8.

 

It noted that swine flu symptoms were experienced by about 1% of the population in England, of which 0.026% died.

Death rate was estimated to be lowest among children aged five to 14 (11 deaths per 100,000 population) and highest among those aged over 65 (980 per 100,000).

(Continue . . . )

 

 

Backing these numbers up is yesterdays HPA (Health Protection Agency) update which stated:

 

Weekly pandemic flu media update

10 December 2009

The HPA estimates a cumulative total number of cases of 795,000 (with a range 380,000 to 1,665,000) since the pandemic began.

 

 

This update, and the subsequent news reports, all seem to be hanging their collective hats on the notion that only 1% of the UK population has had `swine flu symptoms’  . . . a remarkable number,  given that roughly 15% of the  US is estimated to have been infected.

 

While I suppose you could make the case for a horrific over estimation of cases by the CDC, it was just a few weeks ago that the HPA announced that up to 1/3rd of school children in some districts may have been infected by the H1N1 virus.

 

This from Fergus Walsh’s Blog, Fergus on Flu  dated November 24th.

 

The Health Protection Agency (HPA) has done blood tests of hundreds of children and parents connected to early school outbreaks.

 

With one school in south west England they tested around 500 people. They found that although around one in 10 children fell ill, three to five times as many got infected and developed antibodies.

 

After analysing this and other data relating to the number of children being seen by GPs, the HPA has now come up with these interesting estimates:

  • Up to one third of children in swine flu hotspots (such as England and the West Midlands) have already been infected with the H1N1 virus.
  • Across the UK up to one in five children has had had swine flu.
  • About half of those who get infected show no symptoms.

 

It is a bit difficult to reconcile a 1% attack rate (and 138 deaths) in the UK when just last month, the attack rate was being listed at somewhere between 10% and 30% of school children.

 

Something obviously is askew here.  


The World Health Organization is counting fewer global deaths than the US is estimating to have occurred within our own borders.  But at least they acknowledge a serious undercount.

 

Good counts, or even reasonable estimates, are hard to come by. Particularly while the pandemic is ongoing.  

 

And I’ve no quibble with the notion that this is – as pandemics go – a fairly mild one.   We obviously haven’t seen anything near the impact of the 1918 pandemic – and this may not even rise to the level of 1968.

 

While I accept that the UK, Japan, China, and the rest of the world may not have good numbers, or have made reasonable estimates, their willingness to blithely use incomplete data as if it represents reality is a disservice to their people, and those working in the public health arena.

 

Officials around the world proffer pandemic numbers that are – at the very least – deceptively incomplete and then wonder why the uptake of vaccine in their nations are so low.  

 

I’m continually amazed that the media so often prints these numbers without comment or bothers to press public health officials about these seeming inconsistencies. 

 

As far as what the `right’ number is, I’ve no way to know.  

 

I suspect the CDC’s estimates are closer to the truth than the UK, or Japan, or China’s numbers . . .  but we probably won’t have a decent handle on the impact of this pandemic for some time.

 

Until then, all reports (regardless of the source) purporting to gauge the impact of this pandemic need to be taken with a large (boulder sized) grain of salt.

 

*****************************************************************

 

Personal Note:   I’ll be away most of today.  My Sister’s spinal surgery following her car wreck is later this morning.   Check with Crof at Crofsblog for the latest news updates, and later today the new FluView numbers should be released.

»» Read More

Gauging The Severity Of A Pandemic

 


# 4133

 

 

Since almost the start of the novel H1N1 outbreak last spring, one of the major topics of discussion has been the severity – as measured by the CFR (Case Fatality Ratio) – of this virus. 

 

In other words, what percentage of those infected (and symptomatic) are likely to die?

 

It is not an easy question to answer, and even though it appears that this virus will go down as `relatively mild’,  we are only six months into this outbreak, and the virus could mutate or change over time.

 

Thus far, however, we seem to be dealing with a high morbidity - low mortality pandemic.   One that – due to a lack of widespread immunity – causes a lot of illness.  But one that doesn’t cause a lot of deaths.


Good news, by almost any measure. 


But there are caveats.  

 

Those that are dying from this virus – even if their absolute numbers are less than a normal flu season – tend to be younger adults and children.  Something quite unusual when it comes to seasonal flu, which typically claims the elderly and frail.

 

While exact numbers are impossible to compile, researchers have published new estimates of the CFR of the novel H1N1 in yesterday’s PLoS Medicine journal.   These numbers give us a range of likely values, not a single number writ in stone.


First, portions of the press release from the Harvard School of Public Health, then some excerpts (slightly reparagraphed) from the PLoS Medicine study.

 

I’ll have a few closing remarks as well.

 

 

Severity of H1N1 flu in US during current flu season may be less than feared

Burden of disease may fall on young children and non-elderly adults

 

Boston, MA -- A new study from researchers at the UK Medical Research Council and the Harvard School of Public Health (HSPH) projects that the severity of the H1N1 flu during the autumn-winter flu season in the U.S. will likely be less than previously feared. The estimates of hospitalizations and life-threatening events in the study are the most accurate to date of the H1N1 pandemic's impact in the U.S. The study appears online on December 7, 2009 in the journal PLoS Medicine.

 

<SNIP>

 

The researchers used two different approaches to estimate these risks. One approach led to an estimate that approximately 1.44% of patients with symptoms of H1N1 flu during the April-July time period were hospitalized, 0.239% required intensive care or mechanical ventilation and 0.048% died. The other estimate found probabilities 7 to 9 times lower, due to the use of different data to estimate how many individuals were sick. Based on these findings and assuming that the virus doesn't change its characteristics, the researchers estimate that the severity of the autumn-winter pandemic wave of H1N1 flu could have a death toll in a range from considerably below the estimated 36,000 associated with an average flu season in the U.S. to slightly higher. Also, unlike seasonal flu, which kills mainly elderly adults, the H1N1 flu could have the greatest impact in children aged 0-4 and especially adults 18-64, a shift toward nonelderly persons that has been seen in prior flu pandemics.

 

"The good news is that, along with previous work by the CDC and others, our work shows that the severity of the H1N1 flu may be less than initially feared," said Lipsitch. However, he adds that between 1 in 70 and 1 in 600 people who are sick with the illness will be hospitalized, and a fraction of those will die.

 

A preliminary version of this article was posted on PLoS Currents (September 25th 2009), a new forum for rapid publication of results designed to aid timely dissemination of important information during the pandemic.

 

Support for the study was provided by the UK Medical Research Council, the UK Health Protection Agency, the U.S. National Institutes of Health and Department of Homeland Security.

 

 

The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A Bayesian Analysis

 

Marc Lipsitch and colleagues use complementary data from two US cities, Milwaukee and New York City, to assess the severity of pandemic (H1N1) 2009 influenza in the United States.

Anne M. Presanis, Daniela De Angelis, The New York City Swine Flu Investigation Team,, Angela Hagy, Carrie Reed, Steven Riley, Ben S. Cooper, Lyn Finelli, Paul Biedrzycki, Marc Lipsitch

<EXCERPT>

What Did the Researchers Do and Find?

By using data on medically attended and hospitalized cases of pH1N1 infection in Milwaukee and information from New York City on hospitalizations, intensive care use, and deaths, the researchers estimate that the proportion of US cases with symptoms that died (the sCFR) during summer 2009 was 0.048%.

 

That is, about 1 in 2,000 people who had symptoms of pH1N1 infection died. The “credible interval” for this sCFR, the range of values between which the “true” sCFR is likely to lie, they report, is 0.026%–0.096% (between 1 in 4,000 and 1 in 1,000 deaths for every symptomatic case). About 1 in 400 symptomatic cases required treatment in intensive care, they estimate, and about 1 in 70 symptomatic cases required hospital admission.

 

When the researchers used a different approach to estimate the total number of symptomatic cases—based on New Yorkers' self-reported incidence of influenza-like-illness from a telephone survey—their estimates of pH1N1 infection severity were 7- to 9-fold lower. Finally, they report that the sCFR and the sCIR were highest in people aged 18 or older and lowest in children aged 5–17 years.

 


Critics will no doubt point out that the CFR estimated from this study ranges from 1 in 1,000 to 1 in 14,000 – depending on which method is used. 

 

The use of self-reported ILI (via phone surveys) casts a wide net , and is likely to catch a lot of non-influenza flu-like illnesses.  That would skew the numbers badly, making the severity of the virus appear artificially lower.

 

Even during the height of flu season, the percentage of samples submitted to the CDC for analysis that come back positive for flu rarely exceeds 30%.    This past week, only 15% of the samples tested came back as positive for Influenza.

 

image

 

Basing your numbers on medically attended and hospitalized cases excludes mildly symptomatic cases, and those who did not seek medical help.  That would tend to make the virus appear more severe.

 

Neither method is ideal. 


But for now, this  may be as close as scientists can come to calculating the CFR of this virus.  

 

For younger adults and children, the fatality rate is several times higher than for seasonal flu.   For those over 65 – who traditionally suffer the most from influenza – the impact is far less than normal.

 

As far as what the `right’ CFR number is.  We may never know exactly. 

 

But over time, scientists will attempt to refine it further.

»» Read More

The Tip Of The Iceberg

 


# 3896

 

 

A reoccurring theme in this blog over the past 5 months or so has been that we really don’t have a very good handle on the number of people who have died from the H1N1 virus. 

 

While the WHO lists `at least’ 5,000 deaths  and the US count from the CDC is  `more than 1,000’, these number are incomplete, and don’t represent the full toll of this virus.

 

And the WHO and the CDC say that with every release of their numbers, but apparently a number of people don’t `get it’. They insist on using those numbers to `prove’ that H1N1 isn’t much of a pandemic or worthy of our concern.  

 

After all, these are `official’ numbers.

 

I’ve laid out my reasoning before on why we undercount deaths, most recently in Dead Reckoning, but before that in Numbers Don’t Tell The Whole Story, and  A Decided Lack Of Data. 

 

The World Health Organization has numerous documents on global mortality statistics available here, but the repeated caveat in all of them is the `lack of completeness and coverage’. 

 


The WHO can only guesstimate the number of people who die every year from malaria, AIDS, dysentery, or  heart attacks.  They are no better able to report the number of deaths due to influenza.

 

Even in the US, where more than 6,000 people die every day, the number of deaths attributed to the H1N1 virus is most certainly an undercount.  When it comes to influenza, only pediatric P&I (pneumonia & influenza) deaths are required to be reported. 

 

And those numbers are considerable elevated since the emergence of H1N1. 

 

image

 

Unless an adult dies in the hospital while under treatment for influenza or pneumonia, their deaths are unlikely to be linked to the H1N1 virus. 

 

And even those deaths are not required to be reported to the CDC.

 

When we get reports out of China, Asia, Russia, or countries in Africa stating the number of H1N1 related deaths, that information has to be tempered with the knowledge that most of these countries do limited surveillance, and reporting.

 

Today, in the China Daily newspaper, we get a WHO official that states pretty much the same thing. That the number of deaths from H1N1 in China (and in the world) are badly undercounted.

 

A hat tip to Shiloh on FluTrackers for posting this report.  

 

H1N1 deaths 'tip of iceberg'

By Shan Juan (China Daily)
Updated: 2009-10-28 07:58

The death toll on the Chinese mainland and around the world from the H1N1 flu virus could be much higher than previously thought, experts warned yesterday.

 

The World Health Organization's representative in China, Michael O'Leary, said the number of reported H1N1 fatalities may be the "tip of the iceberg".

 

He made the warning yesterday, one day after the mainland reported its third official H1N1 death.

 

O'Leary said the fact that many deaths around the world are not being scrutinized with lab tests means most H1N1 deaths likely go unrecorded.

 

So far, the world has reported 5,000 H1N1 deaths.

 

Zeng Guang, chief epidemiologist with the Chinese Center for Disease Control and Prevention (CDC) agreed, saying lab limitations mean some flu deaths may not be followed up in the lab.

 

"So far, no clear evidence can prove that, but the underestimation of H1N1 deaths, if it is happening, is definitely not intended," he said.

 

The Hong Kong Health Department has estimated that the number of undiagnosed flu cases could be 25 times higher than the official number. The mainland has not estimated how many cases slip under the radar.

 

(Continue . . . )

 


This article uses the .4% CFR (4 in 1000) as an estimate, but again, no one really knows what that number is. 

 

Seasonal flu is thought to claim about 1 life in 1,000 (.1% CFR) infections.  But that varies from year to year, and once again, that is an estimate (and by no means universally accepted).

 

Here in the United States, and in most of Europe, a .4% CFR is probably far too high.  In China, or Africa, that number could actually be low.   It is just too soon to tell.

 

The CDC is intentionally vague on the number of H1N1 deaths in the US, simply because they know that they aren’t counting all of the cases.  

 

But what seems abundantly clear is that we aren’t seeing huge numbers of deaths. This pandemic (for now) appears on a par with 1968 (or perhaps 1957),  but certainly not 1918.

 

After this pandemic is over, I’m sure analysts will dissect the existing records and try to come up with a better number.

 

But even so, that will be an estimate, not an actual count.   And that number will no doubt spark debate for years to come.

»» Read More

Dead Reckoning

 

 

# 3817

 

 

 

Dead reckoning (DR) is the process of estimating one's current position based upon a previously determined position, or fix, and advancing that position based upon known or estimated speeds over elapsed time, and course. - Wikipedia

 

One of the ploys of the pandemic deniers is to use the `official’ tally of deaths, both here in the US and around the world, to `prove’ the H1N1 virus is not a genuine threat.  

 

After all, as of October 2nd, even the WHO (World Health Organization) can only come up with a little more than 4,100 deaths worldwide since this outbreak began in April.

 

And they should know, shouldn’t they?

 

Unfortunately, they don’t.  No one does. 

 

Why?  Because we aren’t trying to count the number of deaths anymore, and even when we were -  back in the summer - we weren’t doing a particularly good job of it.

 

This is a problem I’ve discussed many times over the past few months, including in:

 

Numbers Don’t Tell The Whole Story
A Decided Lack Of Data
Measuring The Severity Of A Pandemic
Arizona & Illinois Report Swine Flu Related Deaths

 

Mike Stobbe, of the AP, has a good article on the problem this morning, which explains that the US, along with many other countries around the world, have quit trying to count pandemic cases.

 

First the article, then some discussion.

 

US, other nations stop counting pandemic flu cases

(October 9th, 2009 @ 2:11am)

By MIKE STOBBE
AP Medical Writer

ATLANTA (AP) - U.S. health officials have lost track of how many illnesses and deaths have been caused by the first global flu epidemic in 40 years.

 

And they did it on purpose.

 

Government doctors stopped counting swine flu cases in July, when they estimated more than 1 million were infected in this country. The number of deaths has been sitting at more than 600 since early September.

 

(Continue . . . )

 

As I wrote back in May, we really have no idea how many people die of influenza during a normal season.  The CDC’s estimate of 36,000 deaths each year is just that – an estimate – an average based on mathematical modeling.   

 

No one counts individual flu deaths.  

 

Every day in the US, somewhere over 6,000 people die from a variety of causes.   Despite the CSI-induced fantasy that every death gets investigated down to the last hair or fiber, the truth is, unless there is reason to suspect foul play or unusual circumstance, most deaths are handled as routine events.

 

If someone dies at home, and they are under the routine care of a physician (the definition varies by state), it is considered `an attended death’. In that case, the patient’s doctor may elect to sign the death certificate without ever examining the deceased, and no autopsy is performed.

 

While rarely stated, there is actually a bit of a built-in disincentive for conducting a post mortem exam. An autopsy could conceivably uncover a missed diagnosis, and that could prove problematic for the doctor.

 

In funeral home parlance, this is sometimes referred to as `burying one’s mistakes’.

 

Even in cases where an autopsy is performed, testing for the influenza virus generally isn’t a part of the procedure.  If there are gross signs of lung inflammation, then pneumonia may be cited as a cause of death.

 

Unless someone dies in the hospital while being treated for influenza or pneumonia, it is highly unlikely that influenza will be listed as an official cause of death. 

 

One exception to this rule is when the deceased is exceptionally young.   Generally speaking, the younger the victim, the more scrutiny we give the cause of death. 

 

Here in the US, pediatric deaths (under age 18) from influenza and pneumonia are a reportable disease.  During an average year somewhere between 50 and 100 pediatric deaths are attributed to influenza. 

 

In 2005-06 there were only 46 pediatric deaths, in 2006-07 there were 78, and in 2007-08 there were 88. 

 

As of last week, there were 128 for this year.   Later today we will get a new tally, and based on yesterday’s MMWR report, that number will jump appreciably. 

 

What is particularly worrying is that over the summer, during a time when we might normally see no more than 1 or 2 pediatric flu deaths, we’ve seen at least 60 due to swine flu.


This grim metric may be our best, most accurate indicator of the impact of the pandemic. It is literally the only individual influenza fatality counting going on in this country, and while it may miss some cases, it is probably fairly accurate.

 

 

image

 

The other prime indicator in the US is the 122 MRS, which monitors the number of pneumonia & Influenza deaths in 122 American cities. 

 

While this monitoring won’t pick up every death, we have good baselines with this model, and should be able to monitor the relative strength of the epidemic outbreak.

 

We’ve other metrics, of course.  The number of P&I hospitalizations, outpatient visits for ILI (Influenza-like-illness), and the like.  But the one metric every one looks to – the number of deaths caused by this virus –  is the hardest to measure.

 

Complicating matters is the fact that (fortunately) this virus appears to be causing a high morbidity-low mortality pandemic. 

 

In other words – it causes a lot of illness - which stresses our health care delivery system and economy,  but relatively few fatalities.  So far, anyway.

 

Deaths, in all fairness, are not the only measure of a pandemic.

 

While the surveillance and reporting of influenza deaths in the US may seem less than optimal, when compared to most of the rest of the world, we are very diligent in these matters.

 

In many nations, medical care and surveillance is rare or non-existent. People die, and are quickly buried, without a cause of death being established. 

 

In Sub-Saharan Africa and parts of Asia, thousands die every day from AIDS, Tuberculosis, Malaria, contaminated water, hunger, tropical diseases and poverty. 

 

No one is counting how many were hurried along this dismal path by influenza.

 

All of this means that the numbers being quoted by the WHO and individual countries (including the US) are practically meaningless.

 

Worse, they are highly misleading.  

 

The truth is, we will never know with any precision how many lives this pandemic will claim.  Just as we have no clear idea of how many died in 1968, 1957, or 1918.  

 

Undoubtedly, over the next few years there will be studies, mathematical models, and estimates proffered by scientists from all around the world. They will be hotly debated in the science journals, among bloggers, and in the halls of academia.

 

At some point, a consensus will be reached, and a number (probably a broad range) will be announced.

 

Only then will we have some idea how this pandemic compares to 1968 or 1957.

»» Read More

Numbers Don’t Tell The Whole Story

 

 

# 3702

 

 

The preoccupation (some might say `obsession’) of a great many people in the scientific world and Flublogia is in coming up with a reasonable CFR (Case Fatality Ratio) for this novel H1N1 pandemic.  

 

And as I’ll demonstrate, it isn’t as easy as you’d think . . . and perhaps, not as important as well.

 

The CFR is the percentage of those infected that die either directly or indirectly due to the virus.   If 1000 people get infected, and 1 dies, then the CFR is .1% . . . which is roughly the mortality rate we see with seasonal flu.    If 10 people die out of 1,000, then the CFR is 1.0%.

 

In 1918, during the worst pandemic in recent history, 25 people out of every 1,000 who were infected in the US died (it was higher in some countries, and lower in others).  The CFR was roughly 2.5%.

 

Early on, the CFR of the novel H1N1 virus was calculated to have been about .4%  or about 4 times higher than seasonal flu.  Today that number is in doubt, although it is still within the high end of some estimates.

 

But the truth is . . . nobody really knows.  

 

We hear assurances that the novel H1N1 virus is `no more deadly than seasonal flu’,  and when you just look at the raw numbers, that may be true. 

 

But numbers don’t tell the whole story.

 

Seasonal flu, which is estimated to claim 36,000 American lives each year, normally takes 90% of its toll among the elderly.  Mostly among those over the age of 80.  Seasonal influenza is, for lack of a better term, a `harvester’ of the aged and infirmed.

 

For centuries pneumonia, which often comes as a consequence of influenza, has been called `The Old Man’s Friend’, simply because it usually takes the elderly quickly, and without much struggle.

 

Pandemic flu, in comparison, often strikes a younger demographic.  In the case of novel H1N1, most of the infections and 90% of the deaths we’ve seen have been UNDER 65.   

 

This is the opposite of what we would normally expect from seasonal influenza, and much harder for a society to accept. We are talking relatively young adults and children dying from a disease that normally kills the elderly.

 

One could easily argue that the death of a child is 10 times (or perhaps a 1000 times) more tragic, and costly to society, than the death of an 90-year-old in a nursing home. 

 

Each year, we lose between 50 and 100 children to seasonal influenza.   This year, up until the arrival of the novel H1N1 virus, we had lost 68 children to seasonal flu.  An average year.

 

image


As you can see, this year, we have a double-spike of pediatric influenza deaths.  Our normal winter spike, and one this summer.

 

Since May, we’ve lost an additional 43 children who have died as a result of the novel H1N1 virus.   A new `counting year’ begins at the end of September, and sadly, this metric may be our best indicator of the impact of the novel virus on our society.  


Pediatric influenza deaths must be reported to the CDC, and so it is one of the few areas where we get an actual, and reasonably accurate, count of deaths. 

 

The rest of the deaths we see reported – among adults – are assumed to be  `the tip of the iceberg’ and not truly representative of the real number.   That’s why the CDC estimates flu deaths every year, because we aren’t set up to monitor and report them.

 

While this age shift to younger adults and children is extremely worrisome, the good news is this cohort is generally stronger, and in better overall health than those in their 80s and 90s, and therefore are less likely to die as a result of influenza infection – seasonal or pandemic.

 

That should have a bit of a dampening effect on the overall CFR, as opposed to a virus that attacked across all age groups.

 

It appears that those over the age of 55 – 65 have some degree of immunity to this virus.  No one knows if that trend will last, but for now, they make up a small percentage of those sickened.

 

The fact that this novel H1N1 virus has (thus far) largely spared the older generation may greatly reduce the total number of deaths, but the age-shifting of the deaths we do see will make its impact far greater than if it were taking mostly elderly victims.

 

For several months in the blog (see here, here, and here)  I’ve been discussing the possibility that we may see a High Morbidity-Low Mortality pandemic. 

 

One that makes a lot of people sick, but claims relatively few, albeit younger, lives.

 

While it is too soon to know with certainty – and this virus could mutate and pick up virulence at any time – right now that is what we appear to be seeing.  

 

I say `appear’, because the tracking and reporting of influenza deaths in this country, and around the world, leaves much to be desired.   Still, despite those limitations, I think we’d have strong anecdotal evidence if this virus were claiming a lot of lives.

 

The 122 MRS surveillance system, which tracks deaths in 122 American cities due to pneumonia and influenza, isn’t showing any huge spike in deaths this summer.  In fact, we’ve remained below the epidemic threshold for most of the past 4 months.

 

image

 

Are we missing some influenza-related deaths, even in these cities?

 

Undoubtedly.  Every day in this country, roughly 6,500 people die from one cause or another. Most will not have an autopsy, and fewer still will be given a post-mortem test for influenza. 

 

Most will be `attended’ deaths, where the victim’s doctor will sign the death certificate (usually without seeing the deceased), and will put down whatever chronic disease they were being treated for. 

 

The death certificate will read Coronary Artery Disease, COPD, or perhaps Myocardial Infarction – and very rarely will influenza even be considered as a contributing factor.   Which is why the CDC estimates flu deaths each year, instead of trying to count death certificates marked with `influenza’ listed as the cause of death.

 

And as many holes as there are in our surveillance systems, the surveillance net from most other countries is even more porous.

 

But despite these shortcomings in global surveillance and reporting, the number of hospitalizations and the number of pediatric deaths – while elevated – remain reasonably low for a pandemic, even in the Southern Hemisphere. 

 

And so it is hard to make a good case for a CFR much higher than that of seasonal flu.   And that is good news.  The bad news is, those that are dying are generally younger, healthier member of society.

 

Skeptics will no doubt use the low CFR to say, `See . . .this isn’t much of a pandemic . . . a bunch of worry over nothing.’  But that misses the point.  

 

If we see the same number of deaths this year from H1N1 that we do in a normal year, and if even half are under 65, that would represent a huge tragedy and loss for our society.

 

I can’t estimate with any accuracy what the CFR of this virus is today (although I believe it to be relatively low), and I certainly can’t predict what it will be this winter and spring.

 


While tracking the total number of deaths is important, we lack the other important number to solve this equation – the total number of people infected. 

 

Between asymptomatic, mild, and untested cases, we’ve no idea what that number really is. 

 

And without that number, we have nothing to divide the total number of deaths into, to derive the CFR.  

 

 

My hope remains that we will be lucky enough to see nothing worse than a Category 1 pandemic.  

 

cdc2

But a CAT 1 pandemic is nothing to be trifled with. 

 

And lest we forget, a CAT 1 pandemic in the developed world is likely to be a CAT 2 pandemic in lesser developed nations.

 

While we obsess over the numbers, and try to quantify the importance and severity of this pandemic, the truth is the numbers don’t tell the whole story. 

 

That would require equating the death of a 10 year-old child or a 30 year-old pregnant woman, to that of a 90-year old nursing home resident.  

 

And while it may sound insensitive, from a societal standpoint, they are worlds apart in terms of impact.

 

None of this, I’m sure, will dissuade anyone from trying to calculate the CFR of this pandemic.  I’m not sure it’s even possible - given the variability of a virus over time and geographic regions – but I do  understand the the need to come up with a number. 

 

Whatever that number is, as long as the age-shift in victims remains pronounced, we shouldn’t try to compare it to the CFR of seasonal flu.  It’s really apples and oranges.

 

When we are talking about a virus that claims mostly young adults and children, we are talking about something else entirely.

»» Read More