A Journey Through The World of Pandemic Influenza

Viral Sovereignty

 

This morning we have an excellent offering from The Washington Post:

'Sovereignty' That Risks Global Health

By Richard Holbrooke and Laurie Garrett
Sunday, August 10, 2008; B07

Here's a concept you've probably never heard of: "viral sovereignty." This extremely dangerous idea comes to us courtesy of Indonesia's minister of health, Siti Fadilah Supari, who asserts that deadly viruses are the sovereign property of individual nations -- even though they cross borders and could pose a pandemic threat to all the peoples of the world. So far "viral sovereignty" has been noted almost exclusively by health experts. Political leaders around the world should take note -- and take very strong action.

The vast majority of repeated avian flu outbreaks the past four years, in both humans and poultry, have occurred in Indonesia. At least 53 types of H5N1 bird flu viruses have appeared in chickens and people there, the World Health Organization has reported.

Yet, since 2005, Indonesia has shared with the WHO samples from only two of the more than 135 people known to have been infected with H5N1 (110 of whom have died). Worse, Indonesia is no longer providing the WHO with timely notification of bird flu outbreaks or human cases. Since 2007, its government has openly defied International Health Regulations and a host of other WHO agreements to which Indonesia is a signatory.

[…]

A year ago, Supari's assertions about "viral sovereignty" seemed to be odd yet individual views. Disturbingly, however, the notion has morphed into a global movement, fueled by self-destructive, anti-Western sentiments. In May, Indian Health Minister A. Ramadoss endorsed the concept in a dispute with Bangladesh. The Non-Aligned Movement -- a 112-nation organization that is a survivor of the Cold War era -- has agreed to consider formally endorsing the concept of "viral sovereignty" at its November meeting.

 

I, along with my fellow PanFlu bloggers [see sidebar] have repeatedly commented on this issue, and I welcomed this piece by two rather "Big Hitters", Mr. Holbrooke and Ms. Garrett. My first post on "viral sovereignty", Viral Cold War, expresses my own, still operative, opinions on the issue.

 

Also from the WP article…

In this age of globalization, failure to make viral samples open-source risks allowing the emergence of a new strain of influenza that could go unnoticed until it is capable of exacting the sort of toll taken by the 1918 pandemic that killed tens of millions of people. As the world learned with the emergence of severe acute respiratory syndrome (SARS) -- which first appeared in China in 2002 but was not reported by Chinese officials until it spread to four other nations -- globally shared health risk demands absolute global transparency.

There is strong evidence from a variety of sources that forms of the bird flu virus circulating in Indonesia are more virulent than those elsewhere and in a few cases may have spread directly from one person to another. The WHO has tried for two years to accommodate Indonesia, without success. Under pressure from scientists worldwide, Indonesia agreed in June to share genetic data on some of its viral samples but not the actual microbes. Without access to the viruses, it is impossible to verify the accuracy of such genetic information or to make vaccines against the deadly microbes.

Outrageously, Supari has charged that the WHO would give any viruses -- not just H5N1 -- to drug companies, which in turn would make products designed to sicken poor people, in order "to prolong their profitable business by selling new vaccines" (a charge oddly reminiscent of the plot of John le Carré's novel "The Constant Gardener"). The WHO has elicited pledges from the world's major drug companies not to exploit international repositories of genetic data for commercial benefit, but this has not satisfied Indonesia.

[…]

The failure to share potentially pandemic viral strains with world health agencies is morally reprehensible. Allowing Indonesia and other countries to turn this issue into another rich-poor, Islamic-Western dispute would be tragic -- and could lead to a devastating health crisis anywhere, at any time.

 

Many of the consequences of the Cold War were morally reprehensible. That is not a "catch phrase" but the simple truth of the past follies of our governments.

 

Have we learned nothing?

 

Apparently not.

 

SZ

Poverty of Aspect

We have exactly one pandemic we can look to that falls under what has been designated the entrance point to be categorized as severe. As defined by the US CDC a severe pandemic hits the threshold when at least 30% of a population falls ill and at least 2% of those die.

 

Just as a Category 5 hurricane begins when winds reach 156 mph (250 km/h) that does not preclude a Cat5 storm from being stronger, or have wind gusts significantly higher, there is no scientific support for the belief that a severe pandemic cannot have a fatality ratio of greater than 2%. In point of fact, there were many places around the world that experienced significantly higher fatality ratios during the 1918 pandemic, it being the one and only example we have to look to with any degree of confidence (such as it is, confidence that is).

 

I titled this entry Poverty of Aspect because, as Karl Duncker coined the phrase, it refers to taking the more restrictive view as opposed to the broader on issues and problems. We see this repeatedly from many of those who make pronouncements about how the next severe influenza pandemic will behave. Assuming our one example defines the outside parameter of all that is possible.

 

Recently I have focused on "The Message", the problems of communicating it, and the failure to heed; I thought I would go ahead and create a category for this phenomenon. With what I heard at the IDSA conference, and what I anticipate I will hear at September's HHS PHEMCE workshop I figure I may be spending a goodly bit of "blogging time" continuing to focus on all things communication and perception, or at least as I see them, understand them, or wish them to be. With the slowdown in the news on the Avian Influenza PanFlu front, I'm also guessing that I will have the time to chew on this at leisure. Not only the time, but plenty of examples to trot out as well.

 

The first place to start is with the above stated 2% fatality rate assumption for an outside parameter.

 

I get the sense that when most people say that a 2% CFR (Case Fatality Ratio) is as bad as it could get they honestly believe it. Furthermore, they believe that in our modern times with all of our modern healthcare and our modern, more hygienic lifestyles, even the 2% CFR is so outside the probable as to be nearly impossible to conceive. But, because 1918 had a 2% CFR (more anecdotal assumption than hard fact) most everyone is left with no supportable alternative but: OK, maybe it could be that bad, but it's not at all likely.

 

A fresh example of this hit Flublogia today [thanks kobie @ FW], this little snip from AScribe Newswire Political Boarders, Health-Care Issues Complicate Pandemic Planning:

    [snip]

In addition to staffing and community coordination issues, the researchers also found that misunderstandings about projected mortality and illness rates are creating panic.

       "In several counties, many planners are anticipating devastating impacts that even exceed the worst case scenarios historically," Avery said. "The confusion results in a sense of helplessness among some planning teams because they believe any planning will be rendered useless by the magnitude of the problem."

       To counter this, the researchers suggested more explanations by federal, state, international and academic experts about statistics and surveillance. [emphasis added]

 

Perhaps the researchers would find it beneficial to do a tad bit of review themselves:

September 2006 WHO report:

Influenza Research at the Human and Animal Interface

[snip]

One especially important question that was discussed is whether the H5N1 virus is likely to retain its present high lethality should it acquire an ability to spread easily from person to person, and thus start a pandemic. Should the virus improve its transmissibility by acquiring, through a reassortment event, internal human genes, then the lethality of the virus would most likely be reduced. However, should the virus improve its transmissibility through adaptation as a wholly avian virus, then the present high lethality could be maintained during a pandemic. [emphasis added]

 

We may not understand the why behind the lethality but that does not change the fact that it is highly lethal. And while there is no way of knowing with certainty what the properties of a pandemic strain of H5N1 would be, it is foolish, in the extreme, to ignore the possibility that a wholly avian H5N1 , though adapted to humans, could retain much, or a significant portion, of its current lethality.

 

The AScribe Newswire report is a providential example of Poverty of Aspect. Because 1918 was only thus and so, nothing can be worse – just ask the government and statisticians.

 

SZ

 

Truth and Flublogia

Truth can be a peculiar thing. Something that always exists, even if elusive or hidden. It exists even if uncovering it is beyond our ability. A "hidden truth" doesn't preclude its existence, just reminds us of our limitations, or at least should remind us.

Depending on a person's philosophical bent, it can be viewed as relative or absolute, but that is more a reflection of the person as opposed to the truth of a matter. Some "truths", in reality, are nothing more than opinions, subjective perspectives: warm vs. cool, difficult vs. easy, etc.

The oft-quoted last lines from Keats' Ode to a Grecian Urn are not even very truthful:

 

"Beauty is truth, truth beauty," - that is all
        Ye know on earth, and all ye need to know.

 

Sometimes truth can be downright ugly, frightening, hurtful, and/or emotionally traumatizing. There is no "beauty" in that sort of truth, yet, it is still "the truth".

 

There is a lot of truth to search for when someone either comes to the issue of pandemic influenza or becomes involved on an ongoing basis, as the netizens of Flublogia (the cyber flu community, and those who [virtually] inhabit it) have. There are scientific, political, sociological, psychological, economic, and legal issues, to name but the "major players". Thus far, none of them have been particularly beautiful, actually just the opposite – ugly they are – at least when viewing from the vantage point of a severe category PanFlu event.

Flublogia does one thing really, really, well: search for the truth. We don't always find it for varying reasons; it may be beyond our technical means, a lack of insider information, an inability to discern private motivations, or wrestling with an event not yet a reality. But even in our failures Flublogia shines brightest when it is engaged in a strenuous search for an elusive truth.

 

I frequently mention "Flublogia", and generally just parenthetically state "the cyber flu community", but what, exactly, is Flublogia? It is the totality of the cyber resources dedicated to all things Pandemic Influenza, almost exclusively directed at the H5N1 strain. That encompasses the blogs, the authoritative with expert/professional authors, the news oriented, and the analysis – opinion oriented (not "hard" lines of demarcation, as we all have occasional forays into each area), and then there are the Flu Forums.

It is on the forums that the real "grunt work" is performed. Issues and unfolding events are picked apart with a thoroughness that would rival that of any obsessive/compulsive. The netizens who frequent them range from doctors, lawyers, and engineers, to homemakers, and retired grandparents, with everything in between (including snarky ex-cops). Collectively it is an evolving demonstration of co-intelligence narrowly focused but expansive enough to be inclusive of everyone who pulls up a virtual chair.

I have had the pleasure and privilege to meet in the world of brick and mortar a goodly number of Flubies (the flu obsessed). My most recent encounter was when I participated at the IDSA Pandemic Influenza conference where six other Flubies either participants or attended as a means of furthering their own understanding. It was a genuine pleasure to meet people who share the same concerns and driven by the same motivations: become informed, learn, prepare, and help others to do the same.

Each flu forum has its own distinctive "flavor" and "core" participants, although many participate on more than one. Aside from the active posters there are many who are referred to as "lurkers", those who read what is posted but don't participate in the conversations, the silent far outnumbering the "vocal".

Although each flu forum has a genuine sense of "community" about it, I can be found periodically throughout the day, and most nights, participating at P4P. When searching for information finding a place that not only has helpful folk, but also a simple and well labeled structure, can mean the difference between success and failure, and P4P has that handily over many of the other flu forums. What good is information if it is too difficult to ferret out?

However, it is probably P4P's honoring of two things that are very near and dear to my heart that recommend it the most (at least for me): The greatest latitude for freedom of speech, and the highest (IMO) ratio of objective over subjective "truth". The latter artfully balanced (mostly) with the former, and opinion is clearly and unambiguously labeled as such.

This is especially important when attempting to "vet" information: are there implications that we should concern ourselves over, if so, how and why they are meaningful. Because, although I am a person who tends to be the sort that seeks a "core dump" of data, at the very core of that core dump is the "why" of why I am digging through the data: What effect does or doesn't this have on me and mine.

In the harsh realities of "truth", we must be ever vigilant for what Francis Bacon knew well in the 17^th century but we, in our time, fail to either appreciate or never even realize:

The human understanding is no dry light, but receives an infusion from the will and affections; whence proceed sciences which may be called "sciences as one would." For what a man had rather were true he more readily believes. Therefore he rejects difficult things from impatience of research; sober things, because they narrow hope; the deeper things of nature, from superstition; the light of experience, from arrogance and pride, lest his mind should seem to be occupied with things mean and transitory; things not commonly believed, out of deference to the opinion of the vulgar. Numberless, in short, are the ways, and sometimes imperceptible, in which the affections color and infect the understanding.

 

In closing, I will draw upon another favorite quote of mine:

The truth is out there…. And so, that's where I can be found – seeking. And, occasionally, even being reminded that what I find too ugly to believe doesn't necessarily mean it can't happen, or isn't true, or potentially so.

 

SZ

News and Information during a Pandemic

My thanks to Lisa Schnirring of CIDRAP for bringing us a report from the recent US Department of Health and Human Services (HHS) tabletop exercise. This event brought together representatives from governmental agencies, health institutions, traditional news outlets, and internet forums and bloggers. The exercise was focused on then needs, dynamics, and interactions of information dissemination during a pandemic. Flublogia luminaries DemFromCT of FluWiki and Fla_Medic of Avian Flu Diary were in attendance as representatives of the Cyber Flu Community's "voice".

From Ms. Schnirring's CIDRAP report:

HHS includes online services in pandemic communication drill

[snip]

The exercise was the second time HHS has reached out to blogs. In May 2007, the department featured posts from bloggers such as Michael Coston of Avian Flu Diary and Greg Dworkin, MD, of FluWiki in a 5-week pandemic preparedness blog series. HHS Secretary Mike Leavitt hosts his own blog on the HHS Web site. He is the first cabinet secretary to use the online forum, according to HHS.

[snip]

"We recognize that during a pandemic information could be life-saving. As more and more people turn to the Internet for information and news, blogs have emerged as an important and influential communications tool," HHS said in its invitation to attend the tabletop exercise.

[snip]

At several points during the exercise, moderator Forrest Sawyer, a former news anchor with ABC and NBC who now runs his own media production and strategy company, Freefall Productions, asked the news media and online outlets to predict what their headlines would be and what information they would need from HHS, CDC, and other agencies.

During the exercise the communications officials from HHS floated the idea of "embedding" some of their staff in media organizations to ease access to official information during a pandemic. The agency also said its media access policies now treat reputable blogs and other reputable online services the same as traditional media organizations.

Stephanie Marshall, director of pandemic communications at HHS, told CIDRAP News that because growing numbers of people are going to online sources for news and information, "It's important for the government to understand how best to work with bloggers and other online journalists to distribute information. The exercise and the insights offered by the participating bloggers will help us improve and refine our existing pandemic communications plan."

 

Fla_Medic (Mike Coston) of Avian Flu Diary offers his own thoughts and observations of the off the record tabletop exercise:

HHS Pandemic Exercise

[snip]

The decision to include the flu forums and Internet bloggers in this exercise was a bold one.   I'm not sure that they know quite what to make of  us yet, but they obviously believe they can't ignore us. 

We are, in their words, `The New Media', and they are working out ways to work with us. 

 

 

As an Influenza Pandemic Blogger and Cyber Flu Community Addict I was nothing short of thrilled to see that the federal government recognizes the internet as something not easily ignored or dismissed and acknowledged the community as having a legitimate "place at the table".

 

Although we cyber "Flu Obsessed" are a small virtual community we can be vociferous, cantankerous, and downright self righteous at times. HHS's first experience with dealing with the Cyber Flu Community was during their Pandemic Flu Leaders Blog, on which DemFromCT and Fla_Medic were Flublogia's blogger representatives as well.

During that first intrepid online experiment there were times that members of Flublogia were so raucous and vitriolic that I found myself actually embarrassed, and for those that don't know me – that's pretty hard to accomplish. There are places within "the community" that I spare myself the aggravation of visiting (out of politeness I will refrain from mentioning them specifically). I find, alternately, their censorship or their "conspiracy theory" nature to be just too much for the Critical Thinking Libertarian region of my brain.

 

Flublogia, the Online Cyber Flu Community, is not without its faults. As such I am appreciative of the government's cautious trepidation in opening the door to us. I applaud their understanding that we are a "force" that isn't going anywhere any time soon so accommodation will, it is greatly hoped, benefit everyone.

During a pandemic, especially the early stages, information dissemination will be vital. At times of crisis and emergency the public's appetite for information is ravenous and insatiable and the traditional press has become sloppy. We in Flublogia, faults and all, do a remarkable and rapid job of "self-policing" in general when measured against the "traditional press". Additionally, we have been around long enough now to be a "known commodity", so while I understand the government's trepidation I am hopeful they are not paralyzed by it and the caution it inspires. Time will tell.

 

As it happens, while I have been composing this entry, I have been listening to CSPAN's program Tonight, Washington where the topic is Influence of foreign media on global issues. The juxtaposition of questions of purpose, credibility, sources, and dissemination between the "traditional" and the "new" media may be serendipitous and coincidental but at the same time informative of the terrible hurdles the government will have to surmount if and when the time comes to actually disseminate credible and timely pandemic information to the public.

I do not envy them their task.

 

SZ

Informed Seats and My Favorite Chair

As I have said a few times over the life of this blog, and more frequently on the flu forums, I believe in what I label the "Viral Tsunami" theory of a pandemic of a wholly avian version of H5N1 that gains the ability to transmit from person to person, H2H for brevity's sake. For my more recent postings supporting this see here and here. Those two posts and this one draw heavily from the UK's recently released National Framework for Responding to an Influenza Pandemic (pdf download here).

In order to qualify as a Viral Tsunami, by my definition, an influenza pandemic would have to have a high Clinical Attack Rate (CAR) and a high Case Fatality Ratio (CFR), as well as encompass a single wave of illness. There is strong belief that the CAR will be between 30-35% of the population and CFR will be no worse than ~2.5%. Because there is strong belief in this scenario as the upper limit of potentials, those figures represent the worst case scenario in so many plans. In addition, I must say, there are many plans that use numbers lower than these as their "upper limits".

 

Part of what the experts in influenza have been doing since 1997, more feverishly since 2003, is studying H5N1 and what makes it so different from what they are used to seeing and dealing with. I have quoted this statement many times from one of the Reveres of EffectMeasure:

"The depths of our ignorance in this age of sophisticated molecular biology is truly impressive."

A lot of basic research is being conducted, or minimally, dusted off and reviewed afresh in light of human infections of H5N1, and at nearly every turn, we discover something else that they didn't know or have to rewrite what they thought we knew.

Part of this journey of exploration and research is aimed at hypothesizing, as informed and scientifically based as is possible, what a pandemic of H5N1 would be like. Unfortunately, many of our experts, scientific and otherwise, base their "guesses" and assumptions on the pandemic of 1918, the last severe pandemic and the only one we have any semblance of empirical data to review. That is, if said experts even credit the possibility of a severe influenza pandemic at the beginning of the 21^st century.

 

CAR, a major component, utilizes a number known as R₀, the basic reproduction number. From Wikipedia:

In epidemiology, the basic reproduction number of an infection is the mean number of secondary cases a typical single infected case will cause in a population with no immunity to the disease in the absence of interventions to control the infection. It is often denoted R₀. This metric is useful because it helps determine whether or not an infectious disease will spread through a population.

If an infectious disease has an R₀ of less than 1.0 it will burn itself out, if greater than 1 it will continue to spread if not mitigated. The UK PanFlu Framework assumes an R₀ than they believe will range from somewhere between 1.4 and 2.2. It is useful to understand that at 2.0 cases will double every one or two days, at 4.0 they would quadruple, etc, on up the scale.

The assumptions of 1.4 – 2.2 R₀ are frightful enough, to say nothing of difficult to address. The same assumptions assume community mitigation measures will have a significant effect on the CAR and R₀, a very reasonable assumption. Modeling suggests the dramatic difference between a local outbreak with and without mitigation:

A lot rides on our plans, the actions we prepare ourselves to take, the plans our leaders civic and governmental leaders will institute on our behalf.

 

What if planning assumptions are wrong?

A reasonable question. We are all pretty much flying by the seat of our pants, some with more well informed seats to be sure, but it is always worthwhile to remember that we cannot know with certainty what the next pandemic will look like. Only in hindsight, or at best as we are struggling in the midst of it, will we know the CAR/R₀/CFR. However, even though we do not have definitive numbers to plug into the all-important variables we do have an ability to extrapolate the unknowns with what we do know, and just about every week what we do know expands.

Expanding knowledge base case in point:

PLoS ONE. 2007; 2(11): e1220.

Published online 2007 November 28. doi: 10.1371/journal.pone.0001220.

A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

John D. Mathews, Et al.

Background

The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R₀ from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R₀.

Data and Methods

On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions.

Findings

We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R₀ of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R₀ in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population.

Interpretation

Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed.

The paper, which includes much more valuable information than I have included in this post, demonstrates that a case can be made for an immunologically naïve population the R₀ will likely be much higher than the planning assumptions. An R₀ greater than 2 will be difficult enough to mitigate and manage, the implications of an R₀ greater than 5 are nothing short of staggering. Fair warning, the R₀ is not the only staggering gem this paper will yield, but they will have to wait for their own post.

Thanks to a knowledgeable reader who was thoughtful enough to take the time to gather, highlight, and briefly explain implications of research, some reaching back 30 years, and sending it along to me, I have an appreciation of this paper's implications that I did not previously have.

One of the areas this reader is exploring is heterosubtypic immunity, while I do not specifically address this in this post, as it deserves its own, it is the core concept of the above paper. For all you intrepid googlers out there a search on "T-cell heterosubtypic immunity influenza" will yield support for what follows in this post.

 

I have assumed a significantly high R₀ and CAR because H5N1, should it gain pandemic H2H ability as an avian influenza, will be novel to human beings. Furthermore, I have been laboring under the belief that 1918's H1N1 had its lower CAR/CFR and cohort specificity because of prior exposures to it, or a close relative.

The epidemiological evidence, such as it is, supports the theory of prior exposure. Now I have been presented with a new (to me) theory explaining 1918's CAR/CFR and cohort specificity: heterosubtypic immunity. My conundrum is that while I am quite partial to the prior exposure/circulation theory, being comfortable with it, like my favorite chair, this theory is supported by more than epidemiological hints and suggestions, akin to nothing more substantial than circumstantial evidence in a criminal prosecution, it is supported by scientific findings.

Scientific findings that still leave us extrapolating into a future pandemic of a yet unknown pathogen, we are still left guessing, but every once in awhile, our seats get a little better informed as we fly by them.

 

SZ <grateful to a thoughtful reader laboring to inform not only themselves but also others along the same path>

Vindication—of Sorts II

Thursday I snuck in my Viral Tsunami theory when most weren't looking. Today I'd like to expound on it a bit. I realize that by just tossing it "out there" it looks even loonier than what it is, although I admit, it's still pretty loony by the standards of accepted wisdom.

See my post Vindication—of Sorts for the accepted wisdom of Pandemic Influenza if you are unfamiliar with it (though I find that impossible).

A/H1N1 was, as best we can determine, an Avian Influenza A virus that had somehow gained the ability to infect humans and be transmitted to other humans, all the genes were avian in origin. It was not a "human" influenza A virus, the sort we get every year, year in—year out. It had an average CFR (Case Fatality Ratio) of 2.5% as best we can determine (yep, there's that phrase again, one I use with regularity).

A/H5N1 is an Avian Influenza virus; all genes are avian in origin. See the Taubenberger paper mentioned a bit farther down for why this is an important distinction when it comes to pandemic influenza.

J Gen Virol 88 (2007), 3094-3099; DOI 10.1099/vir.0.83129-0

Origin of highly pathogenic H5N1 avian influenza virus in China and genetic characterization of donor and recipient viruses

Muhammad Mahmood Mukhtar et al.

 

ABSTRACT

Genetic analysis of all eight genes of two Nanchang avian influenza viruses, A/Duck/Nanchang/1681/92 (H3N8-1681) and A/Duck/Nanchang/1904/92 (H7N1-1904), isolated from Jiangxi province, China, in 1992, showed that six internal genes of H3N8-1681 virus and five internal (except NS gene) genes of H7N1-1904 virus were closely similar to A/Goose/Guangdong/1/96 (H5N1) virus, the first highly pathogenic avian influenza (HPAI) virus of subtype H5N1 isolated in Asia. The neuraminidase (NA) gene of Gs/Gd/1/96 had the highest genetic similarity with A/Duck/Hokkaido/55/96 (H1N1-55) virus. The haemagglutinin (HA) gene of Gs/Gd/1/96 virus might have originated as a result of mutation of H5 HA gene from A/Swan/Hokkaido/51/96 (H5N3-51)-like viruses. The PA gene of H5N3-51 virus had the highest similarity with Gs/Gd/1/96. This study explains the origin of first Asian HPAI H5N1 virus in Guangdong by the reassortment of Nanchang (close to Guangdong) and Hokkaido (Japan) (H1N1-55 and H5N3-51) viruses. Genetic characteristics of donor and recipient viruses were also studied.

A graphic representation of the author's conclusions on where the genes for HP H5N1 came from (credit: the above paper and authors)

As shown, the genetic makeup of HP A/H5N1 is entirely avian at this time, coming from ducks, swans, and geese via reassortment events.

No one knows the why behind HP A/H5N1's incredible virulence, that's a mystery they are still trying to figure out. Of the WHO confirmed human cases ~60% die, many of them with medical attention. Unfortunately, we are struggling to try to understand while being hobbled with lack of autopsy findings. When we do get news of autopsies the news is far from comforting, as these new findings out of China published in The Lancet attest:

The Lancet 2007; 370:1106-1108

DOI:10.1016/S0140-6736(07)61490-1

Comment

Pathology of human H5N1 infection: new findings

Wai Fu Ng and Ka Fai To 

 

[snip]

 

The pathogenic mechanisms of this highly fatal infection remain unclear. The concentrations of inflammatory mediators related to an innate immune response in fatal cases were higher than in non-fatal cases. High concentrations of cytokines in the blood and the innate immune responses might contribute to pathogenesis.3,4,9 In the adult patient who died on day 9 of disease in Gu and colleagues' report, the finding of sparse infected pneumocytes in the lungs contrasted with the severe and widespread histopathological changes of diffuse alveolar damage, which is consistent with a late phase of viral eradication in an immunocompetent host. [Emphasis added]

 

Though viral load was far less than expected damage from the human immune response was massive. Whatever it is about HP H5N1 the human lungs do not like it at all, even small amounts of infected pneumocytes appeared to trigger the cytokine storm leading to ARDS which is highly fatal, as it was in this case. The body kills itself in the attempt to kill the viral invader.

We have a highly lethal virus, no questioning that. Many believe, even many experts, that for H5N1 to gain human-to-human transmission it must give up most of its lethality, but there is no sound scientific basis to believe it, much less officially act upon it.

September 2006 WHO report:

Influenza Research at the Human and Animal Interface

[snip]

One especially important question that was discussed is whether the H5N1 virus is likely to retain its present high lethality should it acquire an ability to spread easily from person to person, and thus start a pandemic. Should the virus improve its transmissibility by acquiring, through a reassortment event, internal human genes, then the lethality of the virus would most likely be reduced. However, should the virus improve its transmissibility through adaptation as a wholly avian virus, then the present high lethality could be maintained during a pandemic.

We may not understand the why behind the lethality but that does not change the fact that it is highly lethal. And while there is no way of knowing with certainty what the properties of a pandemic strain of H5N1 would be, it is foolish, in the extreme, to ignore the possibility that a wholly avian H5N1 , though adapted to humans, would retain much of its current lethality.

 

So, that's the support for my supposition of a highly lethal PanFlu H5N1. Why do most experts believe otherwise? Mostly because 1918 H1N1 had an average CFR of 2.5%, although variable by location and cohort, the overall average is estimated at 2.5%. Logically the expert assumption does not make sense, do we assume all cars perform like a 1966 Volkswagon Beetle? Perhaps if that were all we have ever been exposed to but I'm sure Lamborghini and Ferrari would argue the validity of the measure. A Straw man argument to be sure, but how else to make the point: you cannot judge all by one.

To use the phrase that has gained some traction in Flublogia: When you quantify all severe influenza pandemics by 1918 you judge all future events by a data set consisting of one datum. Should your curiosity be piqued and you are not yet familiar with why 1957 and 1968 influenza pandemics are not valid comparisons see 1918 Influenza: The Mother of All Pandemics Taubenberger et al.

In my previous post I stated that the UK SAG report chose to base their recommendations on the one wave model, not the more generally accepted three-wave model. Again, three waves is often viewed as de rigueur for modeling and planning purposes. I have always discounted the three wave model because of our three times greater world population, mass transit, and the existence of large-to-mega-cities.

The only way I can see a multi-wave pandemic is if we can mitigate the effects down to 5 – 10% of the population being infected, known as CAR, or Clinical Attack Rate.

Again, drawing upon the UK's SAG modeling, they model the CAR at 50%. However, buried in their findings paper OVERARCHING GOVERNMENT STRATEGY TO RESPOND TO PANDEMIC INFLUENZA ANALYSIS OF THE SCIENTIFIC EVIDENCE BASE

Issued by: Civil Contingencies Secretariat Cabinet Office is this little gem:

 

4.35 The value of the basic reproduction number R₀ currently being used by other countries planning for a pandemic ranges from 1.4 – 3.5, although the scientific basis for the value selected is not always clear. Pandemic modelling has tended to work on the basis of R₀ 1.8 to 2.534. Based on expert views in SAG, the UK's assumption for R₀ has been close to 2. The general consensus is that a future pandemic would be expected to have an R₀ in the range 1.4 - 2.2. Depending on the detailed model used, this could lead to a national infection attack rate of the order of 80%.

 

 

4.36 The combination of an 80% infection attack rate and a figure of 67% for the proportion of these showing clinical symptoms (based on the higher estimates from surveys of those in previous pandemics and outbreaks of seasonal influenza) suggest an upper limit for the national clinical attack rate of the order of 50%35. While such a figure would be extreme for the national epidemic, planning to this figure also allows for variation in local infection transmission rates which may generate local attack rates in excess of the national average in some areas.

 

³² Assuming that in a pandemic situation initial immunity in the population is negligible.

³³ Based on comparisons with the epidemic in the United States.

³⁴ Because models are fitted to actual historical data, the variation in different model results for different estimates of Ro is less than might be assumed given the spread in the numerical estimates of Ro. The range of Ro-s used within a particular model is, however, significant.

³⁵ In special circumstances however, for example enclosed communities, a much higher figure closer to 90% has been observed in previous pandemics.

But above these two paragraphs is this one:

4.26 This case fatality ratio is based only on cases that have come to medical attention, and medical intervention has often been late. Theoretically, there might be cases of infection without serious symptoms that therefore go undetected. This would reduce the case fatality rate. However, as more countries institute monitoring of people in the vicinity of an avian outbreak of H5N1 and fail to detect asymptomatic infections and as more population surveys from H5N1 endemic areas fail to reveal asymptomatic infections, this seems so far unlikely.

It the last paragraph they admit to the unsettling fact that we just haven't found the number of asymptomatic infected H5N1 people that were assumed to be out there. Not that they aren't out there, somewhere, we just haven't found but a few, and they have been aggressively searched for.

Therefore, if the UK's scientific findings support the assumption of a CAR of between 50 and 85% then it's safe to further assume those will be sick people, and thus far, a majority of the sick have died.

 

For my reasoning of a CAR of 70 – 90% and the supporting R₀ I will expound in the next posting as this one is already far too long, even for me.

 

As succinctly as I could manage for a mish-mash of supporting data my Viral Tsunami theory, which is made up of following:

• One wave of infection
• A CAR of 70 – 90%
• A CFR that remains high, although ~1/2 of its current 60%.

   

 

So, while I may be a LOON, I am not the only one who has lain out the evidence for the possible horror this would visit upon humanity. However, even though I do feel a certain vindication that others have spotted the discrepancies of official statements, assumptions and plans, I take no comfort in my vindication.

 

SZ

 

Vindication—of sorts

I have long spouted off, sometimes quite "energetically", my opinion that PanFlu planning assumptions tend to be naïve and ill informed. Of late I content myself with gratitude that officials have come to realize that a severe influenza pandemic is possible even in the 21^st century, something that was not a broadly accepted fact two years ago.

 

What constitutes a "severe influenza pandemic"? The well-trodden statistics of at least 30% of the population becoming ill and at least 2% of the ill dying represent the CDC's (the Centers for Disease Control-US) threshold for a Category 5 (severe) pandemic. For the United States that would be 90 million ill and 1.8 million deaths—or more. As I said, these are well-trodden figures. Perhaps too trodden. Do they even register anymore?

 

In the interest of full-disclosure, I admit that I subscribe to the Viral Tsunami theory of an H5N1 influenza pandemic, a theory that is in direct opposition to "accepted wisdom" (or lack thereof).

Accepted wisdom: CAR (Clinical Attack Rate) = 30%, CFR (Case Fatality Ratio) ≤ 2 – 2.5%, R₀ of 2 – 3 (Basic Reproductive Number), and three successive waves of local epidemic presentation per geographic location.

Viral Tsunami: CAR = 70 – 90% (based on a truly novel human pathogen, which A/H5N1 is at this point in its genetic makeup), R₀ of 3 – 9, CFR = 30%, and a single wave.

Again, in the interest of full-disclosure: Only a few of my Fellow Flubies believe the Viral Tsunami is even possible, and none believes it the most likely PanFlu scenario, or at least none have been brave enough to publicly state it where I have had the opportunity to read it if they do. A dichotomy of sorts: Flublogia is stuffed to the brim with folks who believe, down to their very marrow, that we face a catastrophic PanFlu event, and yet their measure of catastrophe is based solely on the CFR, usually somewhere around 100%, but beyond that, they pretty much reside squarely within "accepted wisdom".

 

Prior to the actual PanFlu event, should one happen, no one knows with certainty what the CAR/CFR/Wave characteristics will be

The UK released its National Framework for Responding to an Influenza Pandemic today (download pdf options here).

[snip from the Forward]

The extent of the uncertainties associated with pandemic influenza is a major challenge for emergency planners and some elements of the UK response will need to be initially implemented with incomplete information and in the context of an evolving picture. The various assumptions, presumptions and response measures outlined in the framework will therefore need to be reviewed and, where necessary, changed as the pandemic develops, further information becomes available and impacts are better understood. The threat itself is also evolving, our knowledge and understanding are improving and new countermeasures are being developed. Response arrangements need to be progressive and we will constantly review and update the framework itself as additional information becomes available.

[snip from Introduction]

Although it is highly likely that another influenza pandemic will occur at some time, it is impossible to forecast its exact timing or the precise nature of its impact. This uncertainty is one of the main challenges for policy makers and planners.

[snip section 2.3]

An influenza pandemic can occur either in one wave, or in a series of waves, weeks to months apart. To inform preparedness planning, a temporal profile based on the three pandemics that occurred in the last century and current models of disease transmission has been constructed (see Figure 1).    `

My vindication comes from the UK's choosing to frame their planning assumptions and recommendations on the one wave model, a huge difference from most planning assumptions: Thirty percent infected spread over discontinuous "waves" for ~18 months.

Now imagine 1.8 million US deaths, the vast majority of which occurring between 2 and 3 weeks time, utilizing the "accepted wisdom" scenario for a severe pandemic as far as CAR/CFR are concerned.

 

I sit here hoping that "accepted wisdom" is correct and I will be judged a LOON of the first order for even entertaining the possibility of a "viral tsunami".

 

SZ

Civil Foul: Not Adequately Informed, Trained, Equipped

 

Some days it is utter torture to have a "day job", and today was one such day. When the news hit the wires that a police department in North Wales was being sued by one of their own over how an outbreak of Avian Influenza was handled by the police and the resultant disease I sat up and took immediate note.

In some respects police work is akin to a "family business". Having been one, being married to a retired officer, the daughter and sister of others, and finally, the mother of a patrol officer, I am naturally interested in most things law enforcement. But when law enforcement also crosses into Avian Influenza/PanFlu I am more than idly curious.

Bird flu officer to sue North Wales Police

Nov 2 2007 by Roland Hughes, Daily Post

A POLICE officer who stood guard outside a farm at the centre of the bird flu outbreak fell ill and are now suing North Wales Police.

There is confusion on my part as to whether there are one or two officers involved. The early stories on the internet indicated two, and the wording of this sentence, as well as a few others, still show what might be "echoes" of that earlier release.

The officer is claiming compensation for inadequate training and a failure to provide them with protective clothing.

A constant issue within law enforcement departments is training. Any well run department has ongoing training for its personnel. Ongoing training can, and should, cover firearms (of course), self-defense, civil and vicarious liability issues, legal issues and changes in criminal law, and in America at least, "sensitivity" training. These are the minimum issues addressed on a rotating training schedule throughout the year by departments that concern themselves with the welfare of their officers and the communities they serve.

Professional departments concern themselves with the wellbeing of their officers. In modern law enforcement it costs a lot of money to properly train a police officer, and when an officer finds him or herself on a department that doesn't take the necessary steps to safeguard their life and health, with proper training and proper equipment, those officers tend to quickly go someplace where they do and that big chunk of training budget expended is lost to that department. Yes, police departments are like any private business; the bottom line counts and funds are not limitless.

But an equally driving motivation is vicarious liability. One of my husband's division assignments was that of Commander of Training, so I am reasonably informed on at least the broad brush stroke issues that I speak. And while any police officer is in constant danger of civil lawsuits, as the Commander of Training being named in a civil action for some "lack" on his part was always an encumbrance to the security and safety of our very home.

Two members of the officers' family also fell ill – and are understood to be included in the landmark legal action lodged against the force.

Wales' first-ever case of bird flu was confirmed on a smallholding near Llanfihangel Glyn Myfyr, Corwen, in late May this year. The outbreak was confirmed as H7N2, a less pathogenic strain of the virus than the deadly H5N1, which struck at a Suffolk turkey farm and is circulating in Asia.

Police immediately set up a 1km cordon around the farm to restrict movement, with officers preventing access and looking after the owners, Barbara Cowling and Tony Williams.

But while officers wore their usual police uniforms, public health staff attended in full protective gear.

Both Ms Cowling and Mr Williams showed flu-like symptoms, but tested negative for the illness.

However, the officer showed similar symptoms soon after visiting the farm, with two family members, including a child, following suit.

Doctors are understood to have indicated the policeman did show symptoms of non-human flu, although public health officials yesterday said not all tests had been completed.

The officer felt he were not given adequate training in how to act in the event of a bird flu outbreak.

I am torn between being excited about the issue of information, training, and protection of and from Avian Influenza being brought to bear on departments worldwide and my sense that I should be outraged over a civil suit for what is, in essence, a case of "the flu". Is some other wife sitting at home worried about losing her home in a civil action over "the flu"?

The Larger Threat demands that police departments inform and provide protection for their officers when faced with the dangers of Avian Influenza, and that is especially true when H5N1 is involved, although this particular incident involved H7N2.

Compared to the cost of some standard equipment issued or made available to police officers, the cost of PPE (Personal Protective Equipment: masks, gloves, bio-suits) are downright cheap. The fact that officers were deployed to the scene of a known biohazard without the proper protection is comparable to sending a police officer out without bullets, Barney Fife aside.

Asked about the legal action, a North Wales Police spokeswoman said: "We can confirm that representation has been made to our legal department.

"The matter is still currently under investigation and therefore it would be inappropriate to comment further."

The North Wales Police Federation, which would support the officers' cases, chose not to comment on the case when contacted by the Daily Post.

Public health chiefs said a total of 17 people showed flu-like symptoms in the wake of the outbreak, and a similar case at another farm near Pwllheli days later.

Chris Lines, of the National Public Health Service for Wales, said it was still not known exactly how many people fell ill, and whether those illnesses were down to the bird flu outbreak.

He said: "We are awaiting the results of serology tests. Essentially, some months after someone has fallen ill, it is a test we can do which shows antibodies you have in your blood.

"If you did indeed suffer the illness, then you will have developed the antibodies. But the tests will take some months to do."

Mr Lines would not confirm whether police officers were among those who had been tested.

 

I will watch this case with great interest, both out of general curiosity and because of very personal reasons. I may be an ex-cop but I am the mother of cop, and mother trumps just about everything.

 

SZ

H5N1: A Reminder of the Threat

Will the threat from H5N1 ever go away? Not until we either solve the problems with our influenza vaccine or we suffer a PanFlu event from it.

H5N1 is getting further and further entrenched in our wild water fowl, and has shown up in other wild birds as well. As long as it is in our wild water fowl it will continue to show up in our domestic poultry flocks on occasion.

No one knows with certainty that H5N1 will ever cause a human pandemic. Strong arguments have been made that since it hasn't yet it never will. People who say that are just as foolish as those who say that it will with equal certainty. Although it is my opinion that the ones who are certain it will are closer to the truth than those who say it won't.

After reading FM's blog entry today, A Predilection For The Young, I was once again reminded of my continual failure to understand how anyone can just blow off the threat as if it doesn't exist except in the heart and minds of the few Flu Obsessed. If you haven't yet read this seminal piece from one of our preeminent PanFlu bloggers please do so, and share it with as many people as you can place it in front of. Although what he writes is emotionally disturbing, at least it was for me, it is of vital importance that what he says is understood, and taken with the seriousness that it deserves.

SZ

Update #1: The 111th Case in Indonesia

Today the machine translations of the Indonesian press (thanks to the hard working folks at FluWiki) report that the father of this little three year old has refused hospital treatment and removed him from their care.

According to one of the machine translated articles the child was sent with medication (Tamiflu), instructions for care, and he is being checked on once a day by local health care personnel.

So, it really does appear that we have had a mild case of H5N1. Egypt has seen several, but not this mild.

The world needs viral samples from this child, as well as a serious effort to attempt to pinpoint his route of infection.