A Journey Through The World of Pandemic Influenza

Zambia: Possible Pneumonic Plague

An interesting bit of news surfaced today that, while infectious disease oriented, it doesn't have anything to do with PanFlu. My thanks to Dutchy @ Flutrackers.com. I ask that it be noted that pneumonic plague has not been definitively identified, the finding is said to be preliminary.

Zambia mystery disease could be pneumonic plague: official

8 hours ago

LUSAKA (AFP) — A mysterious disease which broke out in the south of Zambia, killing four people, is now suspected to be pneumonic plague, the health ministry said Friday.

Ministry of health spokesman Canicius Banda said preliminary findings indicate that the disease that has killed four people and affected over 60 patients could be pneumonic plague but the findings were not yet conclusive.

"Our preliminary findings point to pneumonia plague," Banda said.

Four people died and 64 others were put under quarantine last week following the outbreak of the disease in Namwala, a small town in a southern province of Zambia.

Banda said the movement of people in the area had been banned with immediate effect in order to contain the disease, which had symptoms of vomiting and backache.

Medical experts had also begun spraying all the houses in the area to get rid of fleas and rodents suspected to be spreading the disease.

The government has also urged people in Namwala to be calm after word went round that the disease could be the deadly Ebola virus, prompting panic.

"We have carried out the tests and it is not Ebola. People should not panic, the situation is under control," Health Minister Brian Chituwo said.

Pneumonic plague, which is fatal if left untreated, develops when plague bacteria infect the lungs, and can cause a public health emergency due to its high degree of contagion.

 

 

Yersinia pestis (plague) comes in three forms: Bubonic, pneumonic, and septicemic; the most common being bubonic, and least lethal. Plague continues to occur in ~25 countries, even in our "modern" times.

 

The US will average a few cases a year in the Midwest. Eric York, an Arizona wildlife biologist died of a plague infection on the 9^th of this month as reported in USAToday.

Had the possibility of the Zambian disease outbreak been listed as bubonic plague I would have only taken a passing interest. My general interest in plague dates back more than a decade when I became aware of the emergence of antibiotic resistant plague on the African continent.

From The Guardian:

Drug-resistant form of plague identified

· Strain can now resist eight major antibiotics
· Discovery raises fears of devastating pandemics

Ian Sample, science correspondent

March 21 2007

[snip]

A multiple drug-resistant form of the plague, one of the oldest and most lethal diseases in human history, has been identified by scientists, prompting fears of devastating future outbreaks that cannot be contained by antibiotics.

Tests on a strain of the disease-causing bacterium, Yersinia pestis, taken from a 16-year-old boy in Madagascar revealed the organism has developed resistance to eight antibiotics used to treat the infection, including streptomycin and tetracyclin.

The bacterium is believed to have become resistant to drugs after swapping genes with common food bacteria such as salmonella, E coli and klebsiella, probably while being carried in the guts of fleas, which spread the disease by biting infected rodents.

The discovery has alarmed scientists who fear multiple drug-resistant strains of the plague may emerge in other countries, leading to highly dangerous pandemics which spread rapidly. Another serious concern is that drug-resistant strains of the organism may be collected by terrorist organisations and released into the air, causing widespread infection [all emphasis added]

The PLosONE paper referred to can be found here.

This map shows the geographic orientation of Madagascar and Zambia:

 

Just one more disease on the threat horizon…

 

SZ

Who Speaks and Holiday Weekend Miscellanea

I have spent a number of days nostril deep in tackling concepts of DNA, and by extension, RNA—influenza's genes are made up of RNA, as well as a more structured understanding of virology. As with much of what I do or know in my life it's "enough to get me in trouble" but not really enough to do me much good. Those of you who may have wondered why I wasn't on the forums that I am known to inhabit with such regularity that is the reason. Enforced "nose to the grindstone".

 

Who Speaks?

I write and participate on the flu forums under the pseudonym SophiaZoe, an iteration of my original pseudonym of ZoeSophia from back when IRC had its heyday, "Life's Wisdom". Since the inception of this blog two other "Sophia Zoes" have shown up with a web presence. That doesn't bother me in and of itself, obviously, I was drawn to the name so they may have been as well, or, it might actually be their name unlike my use of it. But I take a certain pride in "being unique" and I would abhor being mistaken for someone else, not to mention that the other SZs might not appreciate being mistaken for me.

 

Anonymity is an ongoing concern, both in general on the internet, and in the Cyber Flu Community specifically. Some have chosen to drop the comfort and security that anonymity affords and step into the public's view. Not many, but some. I gave up my anonymity back in the spring and haven't regretted the decision. What I have regretted is that I have a certain "web presence" under my pseudonym so even though I would like to switch to my real name I feel it is important to maintain SophiaZoe for the sake of continuity.

I will, however, content myself with "introducing" myself to all of you, as the next best thing.

Debi Brandon

48 years of age

Wife, mother, grandmother

 

The picture was taken with the crappy camera that comes with the Iphone. Honestly, it is so crappy that I don't understand why they even bothered to include it. Oh, and for the record: While I do have gray hair, which I wear with pride, it's not as gray as it appears in the photo, strange lighting and crappy Iphone camera. However, I thought it added a certain "air of distinction" and rather liked the effect so this is the picture I chose to share.

 

As it says in my "About" page on this blog I was a police officer back in my "younger days", I married a cop, I am the daughter, sister, and mother to others, past and present. I have seen heroic goodness, heart-rending tragedy, and frightful depravity; often the family conversations would curl the toes of most people. I exist in an insular and "unique world", and unavoidably, sometimes that "uniqueness" shines through.

My formal education was in Computer Science, but that was so long ago that technology has left me in the dust. Now when something goes wrong with one of my computers I turn to the Geek Squad—or buy a new one. Speaking of which: my "work-horse" laptop went to visit The Geek Squad and I am working on my "travel laptop", a Vista based machine. Vista—what a crappy OS—I spend more time re-booting than I do accomplishing anything.

While I will continue to post under the pseudonym of SophiaZoe, I did what to introduce myself, as I no longer feel that anonymity is necessary or especially helpful to the furtherance of PanFlu information exchange.

 

Debi (aka: SZ)

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

 

A Public Dialog (US) for PanFlu Vaccine Prioritization

The public is invited to participate in a "web dialog" on the HHS's PanFlu vaccine prioritization recommendation. The dates are December 4 – 6 2007 and the general information can be found on the tabbed sections of the home page.

Participation does require registration and some of the demographic information will be public. They are soliciting two types of participants: "Discussants" and "Observers".

I encourage everyone who is able to join in the "conversation". I hope to "see" you there.

 

SZ

WHO Fails to Sway Indonesia

Reuters released a tiny blurb a few hours ago: WHO fails to reach an agreement with Indonesia over sharing H5N1 viral samples. No surprise.

GENEVA, Nov 23 (Reuters) - Health officials have failed to reach agreement on a new system to ensure developing countries benefit more from sharing bird flu viruses used to develop vaccines, the World Health Organisation said on Friday.

"Nobody can fault you for not trying ... It is so close, yet so far away," WHO director-general Margaret Chan told the final session of a four-day meeting. (Reporting by Stephanie Nebehay; Editing by Jonathan Lynn)

It reminds me so much of Turkey's stand with the US when it requested that US troops be allowed to stage on their border, and launch an invasion from it into Iraq. Turkey kept telling us no because they wanted thus and so, and couldn't imagine that the US was in any position to deny whatever they requested, the US kept saying no because they couldn't imagine that such a good ally would deny us such a vital request. In the end, neither got what they wanted. Turkey was shocked the US turned down their demands, the US was shocked Turkey refused their request.

From this side of the issue I found the wording quite interesting. According to WHO the international body "failed to ensure developing countries benefit more from sharing viruses used to develop vaccines". Reading those words it is easy to interpret that the world does not want to share any of the scarce vaccines, which is simply not the truth.

Depending on whose figures you choose to read—and believe—the world will have between 500 million and 1.2 billion vaccines should the pandemic happen in the near future (1 – 3 years). The low figure is pretty much where we are now, the high represents a year or two out and if everything happens perfectly with new processes and adjuvants (still in trials and not yet approved). Therefore, I would assume the true figure rests somewhere in the middle of the two figures.

Indonesia has a population of ~250 million so that breaks down to either half or twenty percent of the entire world's yearly production of PanFlu vaccine.

Indonesia has complained that when it wanted to buy Tamiflu the "rich countries" had bought up all of the supply. Perhaps… but Tamiflu was supplied by Roche on a first-come-first-serve basis. Moreover, there is the simple fact that Roche donated 3 million Tamilfu treatment courses to WHO for rapid deployment. To say nothing of this little tidbit:

From USAToday 07Dec05:

[snip]

Tamiflu is not patent protected in some countries, including Indonesia. That means the drug can be made there without compensation to Roche. Indonesia has said it would make its own Tamiflu for domestic consumption.

This from People's Daily Online 16Dec05:

[snip]

Indonesia has sufficient stock of Tamiflu tablets for remedy as well as license from the Swiss drug maker Roche Holding for production of the tablets.

According to Health Minister Siti Fadillah Supari, Indonesia would produce anti-bird flu vaccine for human next year. "We will produce the vaccine in January and the vaccine can be marketed in December."

Indonesia is also nearly free from polio outbreak, after the country vaccinated over 24 millions youngsters nationwide in three rounds during the last three months.

The World Health Organization says that the drives have significantly decreased the development of the polio virus and recommended two more rounds soon, in order to completely reach the possible un-reached youngsters during the three rounds.

"We will continue [polio] (the immunization). All funds needed have been obtained, " Health Minster Siti Fadillah Sufari said, adding that 70 percent of the funds was donated by the World Health Organization (WHO), the United Nation Children of Funds and international rotary organizations, while the rest was from state budget.

"After March we will be free from polio," said Fadillah.

In addition, let us not forget the (USD) 10 billion for Tsunami relief in international aid, Indonesia being the recipient of much of that aid.

The country of Indonesia is a mess, there is no arguing it is a country in need of international aid, which it receives, as much of the world is generous to people in need.

I am in favor of free enterprise, capitalism, and all that; if you have something that someone wants there is generally an exchange of value, monetary or otherwise. However, at the same time I subscribe to the belief that when there is need those that can remedy the need should do so, most religions have the concept of "good works", some integrated as a required tenant. Indonesia has been the recipient of many "good works", governmental and NGO; it's Indonesia's turn to answer a call of need.

Roche gave up its patent so that Indonesia could manufacture a drug that the world is scrambling for; I applaud Roche for such action. Had they not I would be, and have previously, advocate for patent busting where Tamiflu is concerned. People's lives should not depend on a further fattening a corporation's coffers, not when there is no reasonable ability to pay.

The simple fact is the world needs the samples for monitoring changes not for pandemic vaccines. A pre-pandemic vaccine will be akin to a bucket brigade fighting a burning barn, better than nothing, and a slim chance of working. The world could just as well make up the less-than-perfect pre-pandemic vaccines from virus samples from Egypt.

Pandemic specific vaccines will come so late and to so few that the issue really isn't an issue at all. Should an influenza pandemic happen before 5 years have passed we will face it naked, or at least the vast majority of the world's citizens will. I will be just as lacking in vaccine as the average Indonesian. As will my husband, and daughter-in-law. Maybe, if we are very lucky, my grandbaby might get one around month 8 or 9 of the PanFlu—maybe. Oh, my son will get one when they vaccinate the First Responders/Law Enforcement—if he avoids infection long enough—and lives long enough. But given his dealings with the public and his age neither of those things are very likely.

No, Indonesia gets no sympathy or understanding from me.

However, the real issue is we need the virus samples to know what is happening with the virus itself. We need to know the changes the virus is undergoing in Indonesia. Is it moving closer to human adaptation—or farther away? Stasis in a virus is not to be hoped for so I do not even consider that a possibility. Is it time to pull out all the stops and gird ourselves for a pandemic or do we still have time? Only analysis of the virus itself will answer those questions.

Of course, I have said pretty the same things many times before. I admit the issue is a "hot button" with me. Mdm. Supari's rhetoric spawns mine, the difference is though, mine represent a few bits and bytes in cyber space, hers may well represent human lives, perhaps even lives that I treasure above my own.

Just as Turkey tried to extort a critical need, so too Indonesia. Perhaps Indonesia would be well served to look up what Turkey got for all of its intractable and exorbitant demands.

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

Thanksgiving in America

Today is the day we celebrate Thanksgiving in America. A day when most families gather around a table strained with weight of a feast lain before them. A day to offer thanks for our blessings.

 

To all of my readers in America: Happy Thanksgiving. I hope this day finds you surrounded by the love and laughter of friends and family.

To my Fellow Flubies: Aside from my own family, you are the greatest blessing that I count.

 

Please remember, as you gather in celebration, the firefighters, paramedics, police, doctors, nurses, deployed and TAD military personnel, who are away from their family and friends protecting and safeguarding ours.

 

SZ

Indonesian Viral Samples and WHO

I have addressed the issue of Indonesia and its refusal to share the H5N1 virus samples that WHO needs more times than I ever thought there would be need of, much less have the words for. However, this issue refuses to go away or find a resolution. My last post on the issue was just last week.

WHO convened a four day meeting in Geneva on Tuesday (20Nov07) to address Indonesia's claims and demands with respect to H5N1 viral samples and vaccine end products, the fifth such meeting this year.

Indonesia claims ownership of any H5N1 virus that exists within its borders. As reported in Reuters:

[snip]

Speaking at the start of a four-day meeting hosted by the World Health Organization (WHO), Indonesian Health Minister Siti Fadillah Supari said developing countries were being denied their "sovereign rights" over bird flu virus samples sent to the WHO, a United Nations agency.

"We must have equitable sharing of benefits arising from the use of viruses through a fair, transparent and equitable mechanism. It is the moral thing to do," she said. (Emphasis added)

A(H5N1) is a virus. A(H5N1) is not an invention or a product of manufacture. A(H5N1) is not an idea, or the product of talent or creativity. A(H5N1) is a virus, oh, and by the way, viruses do not even meet the biological requirements of a life form.

Put bluntly: The sovereign country of Indonesia did nothing to invent, create, manufacture A(H5N1), nor did any of its citizens. In fact, just the opposite, a great deal of effort and money has been expended by Indonesians to eradicate the virus, much of the funding, expertise, and equipment to do so was donated by the international community.

In my previous posting I quoted the WIPO (World Intellectual Property Organization) finding (PDF link) explaining the fallacy of holding Intellectual Property rights over a naturally occurring virus, and I won't belabor the point once again—although I am sorely tempted just to express my own personal indignation over this entire concept.

Now, as far as I'm concerned, Indonesia can KEEP the damnable virus, as long as they KEEP it within the confines of their nation's borders.

For the "moral" aspect, I will draw upon a few comments by some of the other major players:

Pacific News Center Correspondent 11.NOV.07
12:04 p.m. Avian influenza continues to worry the Asia Pacific region's health officials. "One of the greatest threats to the survival of the human race," is how Dr. David Nabarro, the senior UN Coordinator for Avian and Human Influenza, told told reporters in Bangkok, and that while "Nations have made progress in containing the virus' spread, there remain some problem areas." [Emphasis added]

Opening remarks at the Intergovernmental Meeting on Pandemic Influenza Preparedness
Geneva, Switzerland
20 November 2007

Dr Margaret Chan
Director-General of the World Health Organization

[snip]

The prospect of an influenza pandemic raises some very big issues for public health. For WHO, the biggest issue is the threat that an influenza pandemic poses for global health security.

Vulnerability is universal. A pandemic will, by its very nature, reach every corner of the earth, and it will do so within a matter of months. As I have said on several occasions: this shared vulnerability calls for shared responsibility, and collective action to fulfil [sic] that responsibility. In terms of the risk of disease, we really are all in the same boat.

[snip]

We must never lose sight of what a pandemic can mean under the unique conditions of the 21st century. SARS taught us how much the world has changed in terms of its vulnerability to the economic and social disruption caused by a new disease.

And SARS was by no means a global event. It was not a pandemic. SARS was largely a disease confined to the hospitals of wealthy cities.

Think of what may be in store. The last influenza pandemic began in 1968. At that time, airlines were not carrying more than 2 billion passengers each year, as they do today. HIV/AIDS was unknown in 1968. Tuberculosis had not resurged as a global threat.

At that time, in 1968, the world did not have the internet, which has spawned global interdependence in so many areas. This interdependence has greatly amplified the economic and social disruption that new diseases can cause.

Pandemics are recurring events. Countries need to brace themselves for a situation where up to 25% of the workforce may be ill at a given time. They have to brace themselves for a possible meltdown of basic municipal services and a slowdown of economic activity.

And this situation will be occurring globally. There will be no fortunate unaffected parts of the world.

[snip]

Analysis and comparison of viruses allows WHO to update reagents and test kits. This contributes to diagnostic precision and sharpens surveillance. The sharing of currently circulating viruses is the only way to monitor the emergence of drug-resistant strains.

But above all, the sharing of viruses is the foundation of risk assessment. The analysis and comparison of viruses give us the first clues, the first early warning, that the virus may be evolving in a dangerous way.

This is our key difference from the past – this capacity to pick up the signal that tells us to gear up our defences and prepare our populations. This is one of the biggest advantages of the advance warning we have been given.

[snip]

We have been given a unique opportunity in the form of an advance warning. We must not – I can say, we dare not – squander this opportunity. The stakes are too high.

How will history judge us, collectively, as an international community, as an agency like WHO, responsible for safeguarding international health security, or as individual countries? As I said, we have a shared responsibility to pursue collective security.

With this question, I also want to give you a challenge. This is now the fifth large meeting, held this year, concerned with the sharing of viruses and access to vaccines and other benefits. Millions of people outside this hall depend on us to make progress. [All emphasis added]

Heartfelt and impassioned pleas from people who carry a heavy burden.

Quoting again from yesterday's Reuters article:

Experts fear the constantly mutating virus could change into a form easily transmitted from person to person and sweep the world in months. A pandemic could kill millions of people, shut down businesses and overwhelm health care systems, they say.

What drives this fear and passion? The simplest answer it's all in the numbers.

Using round numbers:

There are six+/- billion of us

If 30% of us become ill that equals 1.8 billion

If 2% of the ill die that equals 36 million dead.

Those figures represent the Centers for Disease Control's (CDC) threshold for a severe pandemic, termed a Category 5 Pandemic on their severity scale of 1 – 5. And, just like with the Safer-Simpson scale for hurricane strength classification, which the pandemic scale was modeled on, there is a lot of severity above the threshold, but once that threshold is breeched it becomes, in many ways, academic. Catastrophic is—catastrophic.

Further reducing human beings to numbers and percentages: Every 1/10^th of 1% of six (+/-) billion equates to six (+/-) million Men, women and children. Living, breathing, laughing, loving and loved, souls.

Those figures (human beings) would drive heartfelt impassioned pleas from my lips as well. Dr. Chan is correct when she framed the issue, not in pre-pandemic or pandemic vaccines, but in seeing this monster come at us. Again, the hurricane analogy is apropos: with several days warning generally afforded for a hurricane people have the opportunity to get out of harm's way. Without knowing a hurricane is coming loss of life is needlessly compounded, even for a moderate hurricane. Pandemics are no different.

In order to see what is (or is not) headed our way pandemic wise viral samples from every human occurrence must be analyzed and vetted by the scientific community. Indonesia has a moral obligation to participate in the scientific early warning system; or to use Mdm. Supari's own phrase: "it's the moral thing to do".

SZ

Pandemic Mitigation II

Last night I addressed pandemic mitigation from a general, community level (here), tonight I would like to discuss the issue on an individual level.

There are 300 million +/- people in the US and according to the 2000 US Census 69% percent of us live in areas that have a population of 50,000 or more, in 3,629 urban areas. For a breakdown of percentage by state see here. I was quite surprised to learn that my state (SC) is the least urban density in the nation—a good thing in a moderate to severe pandemic.

 

Using official estimates of what could be anticipated for a severe pandemic a 30% CAR (clinical attack rate) and 2% CFR (case fatality ratio) we can glimpse into our crystal balls and see what might be in store for our states and our cities.

For my area, the city, (Charleston), has 425,000+/- residents. That would mean that my city would see roughly 127,500 PanFlu illnesses and 2,550 illnesses directly attributed to those illnesses. Were I to figure it for the entire area, known locally as The Tri-County the figures are as follows: 603,500 residents, 181,050 PanFlu illnesses, and 3,621 PanFlu deaths.

Of course, we have no way of knowing what the CAR/CFR of the next pandemic will be, should one occur, but currently H5N1 has a cumulative CFR of just over 60%. Assuming a pandemic of H5N1 for my purposes here, a drop of 90% in the current CFR would still leave us dealing with a CFR of 6%, and that would translate to 7,650 deaths for my city and 10,863 for my entire area. When I type "deaths" and you read "deaths", it is important to remember that those numbers represent people: men, women and children. In the case of the figures I quoted those are my neighbors, co-workers, friends and family members.

 

I went through all the effort to type all of the above out because I feel it is important to be crystal clear about what I am addressing in this entry, what we, as individuals, can do to reduce our chances of being included in our community's statistics.

 

So, what can we reasonably do to protect ourselves? Until we have a vaccine released to our demographic/cohort, (for a draft guidance of vaccine priority sees here), we will have to rely on Non-pharmaceutical Interventions—NPI's.

• Keep your children out of school no matter what your school's official policy is. Not only are children the most efficient spreaders of influenza, schools are over crowed and perfect amplification points for any infectious disease.
• Maintaining social distancing: 3 feet or more.
• Frequent hand washing
• Avoiding touching our faces
• Avoiding touching common surfaces: anything someone else may have touched. Both influenza A and B viruses survived for 24-48 hr on hard, nonporous surfaces such as stainless steel and plastic but survived for less than 8-12 hr on cloth, paper, and tissues. Measurable quantities of influenza A virus were transferred from stainless steel surfaces to hands for 24 hr and from tissues to hands for up to 15 min. Virus survived on hands for up to 5 min after transfer from the environmental surfaces. J Infect Dis. 1982 Jul;146(1):47-51
• Use alcohol based hand sanitizer liquid or gel any time you touch a common surface
• Work from home if at all possible
• Stay home if possible (known as SIP or Shelter in Place by Flubies)
• Minimize physical contact
• Wear a mask: N95, surgical, homemade (in order of effectiveness and difficulty of obtaining during a pandemic) My blog entry for the CDC's offering on a homemade mask here, and a discussion thread about masks, as well as tossing around ideas on mask workarounds in general on P4P here.
• Stay home if you become ill with any illness; you will not know if it is PanFlu or not for a day or three and you do not want to be out spreading germs.

   

 

Will doing these things guarantee you will not get PanFlu should we suffer a pandemic? I cannot give you a definitive yes to that question, but they will reduce your chances of becoming infected, and short of an effective vaccine, that is probably the best we will be able to manage—reduce our chances of becoming infected. An aside: For the latest release on the steps and timeline involved in producing a PanFlu vaccine see the WHO's PDF here; the pandemic is likely to be over before we have an effective vaccine.

 

 

Here's hoping none of us end up as a PanFlu statistic.

 

SZ

Pandemic Mitigation

I received an email from a long time Fellow Flubie last night that brought to light something that I have been woefully silent on, Non-pharmaceutical Interventions or NPI's for brevity's sake.

Two things drive the severity index of a pandemic: CFR (Case Fatality Ration) and CAR (Clinical Attack Rate-% of population symptomatically ill). See the CDC's (The Centers for Disease Control) influenza pandemic severity graph:

Generally the CAR for pandemic influenza is estimated at 30%, the figure represented in the CDC's severity index graphic, the fine print is that it is likely to be 30% or higher in the general population. Many statements on likely CAR leave off the or higher part.

The clinical disease attack rate will likely be 30% or higher in the overall population during the pandemic. Illness rates will be highest among school-aged children (about 40%) and decline with age. Among working adults, an average of 20% will become ill during a community outbreak. (PandemicFlu.gov)

These figures are estimates of what the percentage of ill will be with no community mitigation strategies.

Policy Review

Nonpharmaceutical Interventions for Pandemic Influenza, National and Community Measures

World Health Organization Writing Group

[snip]

Transmission Characteristics of Influenza Viruses

 Most information on transmission of influenza viruses is based on older experimental studies, inference from observations during outbreaks, and studies with other objectives, especially the assessment of vaccine or drug efficacy. These sources have substantial limitations: investigations often used different methods, involved small numbers of persons, and reflected the behavior of influenza A and B viruses in seasonal rather than pandemic settings (the level of preexisting immunity in populations is substantially higher in seasonal epidemics). For this reason, data from young children, who presumably lack prior exposure and therefore immunity to influenza, may better reflect illness and viral shedding patterns of pandemic disease. The "infectiousness" of patients is virtually always inferred on the basis of viral shedding from the upper respiratory tract rather than from directly observed transmission, but the relationship between nasopharyngeal shedding and transmission is uncertain and could vary. Detailed studies of lower respiratory tract virus loads, particularly relevant to small-particle aerosol transmission during coughing and sneezing, are not available. In many studies, the preexisting influenza antibody status of study participants is not reported, even though this factor is critical in influencing illness and viral shedding patterns. In controlled studies, in which susceptible study participants are typically screened for preexisting influenza antibody by hemagglutination inhibition assays to the challenge virus, the routes of infection and the challenge virus can differ. Other factors that differ among studies are the age and preexisting medical conditions of study participants and the timing of specimen collections for virus testing.

 

We look to our experts to give us their best estimates based on what is known and they do a fairly good job of it. Granting that, however, it is important to us, as individuals, to understand that the estimates are nothing more than informed guesses. No one, no matter their level of expertise or field of specialty knows, with certainty, what proportion of our population will become ill.

 

Given that we could reasonably assume 30-50% of our community could be actively infected with a pandemic strain of influenza (non-mitigated) and the likelihood of having access to vaccines in time to do the majority of us any good at all is slim—at best—it is incumbent upon us, as individuals, to understand mitigation strategies and accept personal responsibility for utilizing as many as we are capable of employing.

 

So, what are the mitigation strategies?

 

There are two levels of pandemic influenza mitigation strategies: Community and personal.

Community mitigation strategies:

 

The anticipated benefit of early and effective community mitigation:

If we interpret the CDC's graph with the following graph we can glean a clearer picture of direct and dramatic benefits.

Graph Credit:

J. R. Soc. Interface

doi:10.1098/rsif.2007.1218

Published online

Individual space–time activity-based modelling of infectious disease transmission within a city Yong Yang, Peter Atkinson and Dick Ettema

 

Existing under the community mitigation strategies will be inconvenient and possibly quite constrictive, but if we prevent our medical resources being overwhelmed and our critical infrastructure from being shut down due to lack of personnel we all benefit. If we prevent our own, or a family member's, illness we benefit personally.

From the Interim Pre-Pandemic Planning Guidance:

The goals of the Federal Government's response to pandemic influenza are to limit the spread of a pandemic; mitigate disease, suffering, and death; and sustain infrastructure and lessen the impact on the economy and the functioning of society. Without mitigating interventions, even a less severe pandemic would likely result in dramatic increases in the number of hospitalizations and deaths. In addition, an unmitigated severe pandemic would likely overwhelm our nation's critical healthcare services and impose significant stress on our nation's critical infrastructure.

 

We'll all be in the soup together and it will take us all doing our parts. We are not helpless and have been given valuable guidelines about what we can expect and what will be expected of us. And even if the pandemic is worse than what has been officially promulgated the benefits will still play—they will just be even more important.

 

SZ