Greg Marmalard: Remain calm! All is well!
D-Day: Ramming speed!

Flu pandemics have become kind of a hobby of mine, not out of morbid interest but because I work in an industry that has to anticipate and model the potential impact of such things and also because I’m part of the team at work responsible for coordinating and communicating responses to a campus-wide disruptions such as fire, earthquake, tornados … or large numbers of employees unable to come to work. As such we get information from groups such as the World Health Organization and from Risk Management Solutions (RMS), a company that does catastrophic risk modeling.

The information that I am receiving from these very credible sources suggests, coupled with what I know of the avian-flu scare, that there is some reason to be concerned but no reason to lose perspective. I’ll share the bad news and good news here, along with a hat-tip to a previous Presidential administration likely to go unmentioned in the media accounts.

All flu viruses — whether our annual garden-variety flu strains or the most deadly ones — arise from animals (like birds or pigs); the virus mutates (called antigenetic drift) as it comes into contact with other organisms and spreads by becoming more communicable each time. I don’t know how many of these strains never develop to where they can be communicable between humans, but I do know that at least one crosses that evolutionary finish line every year. Generally these are comparatively mild but the potential is always there for a nasty strain. Indications are that this current version (identified as an A/H1N1), while called a Swine Flu, is actually a combo platter of Swine and Avian Flus and of strains already found in humans — this makes it more communicable, but also means we’re likelier to have more natural resistance.

Good news:
A/H1N1 is not H5N1, nor has it reached pandemic status yet. While people are dying from this (none so far in the U.S.) the early projections, hampered as they are by limited data so far, suggest that if it becomes a pandemic it will a moderate one with a chance to become severe. As RMS notes:

A typical ratio of actual cases to those hospitalized is likely to be between 2 to 10. This would give a case load estimate of between 3,000 and 16,000 people infected, and would suggest that the virus virulence is between 3.4% and 0.6% Death per Case. As context, the 1918 pandemic had a Death per Case of 2.5%, so when case loads are properly counted this virus could turn out to be as virulent or worse than the 1918, but it is more likely to be of significantly lower virulence. It seems to be considerably more deadly than normal seasonal flu, which has a DpC of around 0.1% but evidently does not have a virulence anywhere near as severe as the H5N1 ‘avian flu’ virus in the outbreak of 2006-07, which had a DpC of over 50%. In general this is likely to be classed as a ‘Low Pathogenicity’ influenza virus.

Another positive, according to Tevi Troy in a commentary in today’s Wall Street Journal, is that concerns about an Avian Flu outbreak as early as 2004 has led to better preparedness today:

Under President Bush, the federal government worked with manufacturers to accelerate vaccine development, stockpiled crucial antivirals like Tamiflu, war-gamed pandemic scenarios with senior officials, and increased the Centers for Disease Control and Prevention’s (CDC) sample identification capabilities. These activities are bearing fruit today.

The Department of Health and Human Services (HHS) has already deployed 12.5 million courses of antivirals — out of a total of 50 million — to states and local agencies. In addition, CDC’s new capacities have allowed Mexican officials to send flu samples to CDC for quick identification, a capability that did not exist a few years ago. Collaboration between the government and the private sector on vaccines — which Mr. Bush and his HHS team actively encouraged — could potentially allow manufacturers to shepherd a vaccine to market within four months of identifying the strain and getting the go-ahead from CDC or the World Health Organization.
…
Another issue: Under the Public Readiness and Emergency Preparedness (PREP) Act of 2006, the government has the authority to issue “Prep Act Declarations” granting liability protection to manufacturers whose products were used in public-health emergencies. This helps encourage manufacturers to develop countermeasures. The government issued a series of such declarations in 2007 and 2008. They protected the development and use of influenza vaccines and pandemic antivirals, as well as anthrax, smallpox and botulism products. The Obama administration should consider granting more of them — if appropriate — in the weeks ahead.

So far it also appears that this strain responds to Tamiflu — there had been concerns that the next significant flu mutation might be resistant.

It’s also worth noting that early indications are that the Initial Virus Reproductive Number (RO) of this outbreak appears to be low, meaning that the number of people infected by the virus by exposure to someone who has it is containable. While they are still tracing the infectiousness of the cases in Mexico, it is so far thought to be below the 1.5 RO of the typical seasonal flu. While the public’s awareness of this flu has increased dramatically in the past few days, reports of the outbreak have been coming in for weeks, suggesting it is containable.

An RO exceeding 1.8, however, is considered “uncontainable”; the RO of the 1918 pandemic was 2.7, while 1957’s was 2.1 and 1968’s was 2.0.

Bad news
It’s too early to judge if there’s really bad news yet, but most of the deaths so far have been in the young to middle-aged adult population. This is a concern because this is typically the healthiest and most-resistant group to influenza — and also the group that had the highest mortality in the 1918 outbreak. While infants and the aged typically account for most flu deaths each year, a return of the Avian Flu could turn this expectation on its head. Part of the theory is that this group is less likely to take the initial onset of the attack seriously and simply try to work through it (even bringing it to work with them). By the time they realize they’re truly sick they may be irreversibly caught in the spiral of a cytokine storm where the body’s own immune system becomes over-stimulated and actually attacks itself, with death occuring in as little as 48 to 72 hours. If this reaction is part of the viral bundle now being handed out it could get ugly. So far, however, pathology of deaths from this flu are being described as “severe pneumonia” (a common cause of death initiated by the flu) and not indicative of a cytokine storm. This is something that is going to be watched closely, however, as things progress.

Also at risk, of course, is the economy — you know, the one that’s been so hale and hearty of late. If you recall the effect of the SARS outbreak a few years ago on the Toronto economy — airports and businesses shut-down, people afraid to leave their homes — the same thing could happen on a larger scale if this progresses. Currently the WHO is studying whether it should raise the pandemic alert from level 3 to level 4 or 5, which would trigger national pandemic response plans that include travel restrictions, border closures, prohibitions on public gatherings (such as sporting events) and would issue drugs to front-line health responders.

The US has declared a Public Health Emergency – one step below the implementation of its full pandemic response plan. Many other countries are likely to ramp up their response measures soon.

More information is available on-line from the World Health Organization and the Centers for Disease Control. You can also review the series of posts I did on Avian Flu a few years back as these are still relevant. As I wrote then: by all means, come to your own conclusions. At the least I think you’ll find this subject is food for thought – and prayer.

Update:

The WHO has raised the Pandemic Alert to Phase 5 (evidence of of significant human-to-human transmission). Phase 6 is the highest alert and describes a pandemic situation (featuring “efficient and sustained widespread human-to-human transmission).

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I’m resolved to be brighter and more bubbly this week, but I’ll pass this on from last Saturday’s The Writer’s Almanac for historical perspective:

It was on this day in 1918 that the first cases of what would become the influenza pandemic were reported in the U.S. when 107 soldiers got sick at Fort Riley, Kansas.

It was the worst pandemic in world history. That year the flu killed only 2.5 percent of its victims, but more than a fifth of the world’s entire population caught it, and so it’s estimated that between 50 million and 100 million people died in just a few months. Historians believe at least 600,000 people died in the United States alone. That’s more than the number of Americans killed in combat in all the wars of the 20th century combined.

No one is sure exactly how many people died, because it wasn’t even clear at the time what the disease was. One of the strangest aspects of the pandemic in this country was that it was barely reported in the media. President Woodrow Wilson had passed laws to censor all kinds of news stories about the war, and newspaper editors were terrified of printing anything that might cause a scandal.

So as the flu epidemic spread across the country, the newspapers barely commented on it. In large cities, people were dying of the flu so rapidly that undertakers ran out of coffins, streetcars had to be used as hearses, and mass graves were dug. In the fall of 1918, doctors tried to get newspapers to warn people in Philadelphia against attending a parade. The newspapers refused. In the week after the parade, almost five thousand Philadelphians died of the flu. The flu might not have traveled as quickly across the country if troops weren’t being mobilized and shipped from base to base.

Among the writers affected by the flu pandemic was Katherine Anne Porter, who grew so sick with the disease that her family had already arranged for her funeral when she managed to recover. The novelist and critic Mary McCarthy got on a train with her parents on October 30, 1918. Her father died of the flu before their train reached Minneapolis. Her mother died a day later. The novelist William Maxwell lost his mother to the flu that year. He said, “It happened too suddenly, with no warning, and we none of us could believe it or bear it … the beautiful, imaginative, protected world of my childhood swept away.”

The 1918 flu is considered to be very close genetically to the current strain of avian flu decimating bird populations throughout Asia and now into parts of Europe. Go to this blog for daily updates and aggregations from a scientific (as opposed to sensational) point of view on what the avian flu is, what is known and what is being done about it.

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A normal but nasty strain of flu is circulating (see here and here ). It appears to run its course in a couple of days but with flu there is also a risk of getting a secondary streptococcal infection leading to pneumonia, bloodstream infections or meningitis, which can be deadly. In fact, with concerns about an avian flu pandemic it is worth noting that many of those who died in the 1918 Spanish Flu outbreak (to which the avian flu is closely related genetically) actually died from pneumonia that set in with the flu.

While pneumonia has been effectively treated with antibiotics in the past, the disease is becoming more resistant. The strongest protection now may come in the form of pneumococcal vaccinations. These won’t prevent the flu virus, but can stop secondary pneumococcal infections from taking advantage of an already weakened victim. The Minnesota Department of Health does an excellent job of providing information about pneumonia shots as well as information on how this can affect the impact of the avian flu.

(HT: Z-Plus Partners Blog).

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Three people have died and 12 others have been infected in an outbreak of avian flu in Turkey this week; the dead, all children from the same family, are the first bird flu deaths outside of Asia. While the relationship between the dead children has raised concern that the virus may be transmmitted from human-to-human, the evidence still suggests this is a case of animal-to-human infection, as reported by the BBC News:

Mehmet Ali Kocyigit, 14, and his two sisters Fatma, 15, and Hulya, 11, have all died this week.

Tests carried out in a UK laboratory confirmed that Mehmet Ali and Fatma died from the H5N1 strain, which has killed more than 70 in south-east Asia and China.

The children’s family kept poultry at their home in Dogubeyazit, close to the Iranian border in Van province.

All four children developed symptoms including a high fever, coughing and bleeding in the throat.

Doctors said they had been playing with the heads of chickens who had died of bird flu.

There is concern by health officials that the concentration of victims may suggest, however, that a strain of H5N1 is circulating that is easier to pass to humans. While this is not the human-to-human mutation required that could lead to a pandemic, it is a serious concern for populations in close proximity to infected (or potentially infected) poultry. Since January 2004, more than 140 cases linked to bird flu have been reported to WHO. More than half the patients died. The WHO is concerned by developments in Turkey but not ready to raise the global alert level at this point, according to spokesperson Dr. Maria Cheng:

Cheng said at this point the WHO isn’t contemplating changing the global pandemic alert status from the current Phase 3 (no or rare instances of person-to-person spread) to Phase 4, where small, localized clusters of cases indict limited human-to-human spread – a development that would suggest the virus is adapting to a human host.

“We’re still at a very preliminary stage in the outbreak investigation. And to move from (Phase) 3 to 4 we’d have to see a substantial change in the virus to know that it’s becoming more adapted to human transmission,’’ Cheng said.

She added that at this point, the WHO doesn’t think the virus is passing from person to person in Turkey.

“Our hypothesis is that we know that this is an area where people raise chickens and that there tends to be a lot of contact between people and chickens,” she said.

“So I think our working hypothesis is that they contracted disease through common exposure. But at the same time we can’t rule out human-to-human transmission.”

Two concise but very informative posts by Revere have appeared here and here on the public health blog Effect Measure that provide a useful update on the situation in Turkey and the possible implications.

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Could the outbreak of the H5N1 virus (avian flu or bird flu) in 57 people in Indonesia be the harbinger of the global pandemic that has had experts throughout the world very concerned for years?

Let’s hope not, but this community of scientists, researchers and doctors is watching developments very closely and holding their breath. At stake, literally, are millions of lives around the world including, by one conservative estimate, 1.7 million in the U.S. (Note: my day job puts me in contact with people who have to concern themselves with projecting this risk, and I’ve helped write articles on this topic for risk management publications. I’ve posted on this subject in this blog here, here and here.)

You can read those posts for an overview, or do your own research (there’s plenty of it out there now) or visit this blog which is aggregating the latest details and research on a daily basis. Here, however, are the pertinent details:

The reason the H5N1 virus has created so much concern is because it is genetically very similar to the virus that created the famous 1918 Spanish Flu pandemic that is generally believed to have killed between 20 and 40 million people world-wide (one modern estimate puts the total at 100 million, however). The impact today could be even more devastating considering the world is much more densely populated now and people are many times more mobile, which could promote the rapid spread of the pandemic.

Despite the genetic similarity, an H5N1 vaccine has yet to be developed. The flu has already killed millions of birds in Asia, and led to the preventive slaughter of millions more domestic fowl. So far – and this is important – the virus has passed to humans only through animal to human contact; it has yet to take a form that allows it to pass from human to human (more potentially good news on this this in a few more paragraphs). Flu viruses, however, are very unstable and mutate easily; every influenza that affects humans – such as the strains that appear annually – began in animals and followed this path. The easiest way for the virus to mutate is to come in contact with a human or animal that already has another strain of influenza active in its body and for the two viruses to become recombinant. (Pigs, for example, have been shown to be able to host both H5N1 and “human” influenza and H5N1 has started to turn up in pigs and tigers in Asia.)

H5N1 infection so far have been mainly in Southeast Asia where many people live and work in close proximity to birds and other animals susceptible to being carriers. Approximately 40 percent of people who have contracted the virus have died.

Here’s why the current cases in Indonesia are significant: Indonesia, unlike other asian countries, refrained from wholesale slaughter of commercial and domestic flocks of poultry thought to be harboring the virus, which might explain the outbreak. While there is still no confirmation of human-to-human transmission, the number of people infected there within a short timeframe is troubling. Also, this spring there were several small outbreaks in Vietnam in “pods” of people. The course of the Spanish Flu was for a few isolated cases in the spring, followed by a quiet summer and then a rapid spread the in the fall.

On a bit more positive note, some virologists think there may be some natural barriers keeping the virus at bay in humans, as noted here:

1. Its viral replication in human cells may be inefficient. There may be too few viral offspring emerging from infected cells to create a big “viral load” that can be spread through coughing or sneezing, as the human flu virus does so well.
2. The avian virus is unable to lock on effectively to human cells, or more accurately certain types of human cells. The spike that enables it to lock on to the cell receptor is the wrong shape.
3. Avian viruses’ natural home is the gut of birds, where the temperature is a balmy 37 degrees Celsius. The human respiratory tract, though, is 33 degrees to 34 degrees Celsius. That coolness could have an impact on how well the virus reproduces.
4. Bird viruses are well adapted to evading the immune system of birds by skirting the molecular tripwires that unleash antibodies and white blood cells that destroy invaders. But they do not yet have this in humans.

This may be good news, but the spread of H5N1 to species other than birds (again, documented in pigs and tigers), and the ability of other influenza strains to make the jump to humans, still raises major concerns.

For a comprehensive look at the havoc a pandemic could create medically, politically and economically, and what can be done to reduce the risks and ultimate impact, I highly recommend you read this article by Dr. Michael Osterholm. Just because the risk is almost mind-bogglingly surreal to consider doesn’t mean it can’t happen. After all, a year ago how many people could have conceived of a tsunami big enough to devastate half a dozen countries, or a hurricane wiping out 80 percent of a major metropolitan area in the U.S.?

Update:

Here’s a report from CNN that suggests that H5N1 is resistant to Tamiflu (oseltamivir), the leading antiviral drug that countries are trying to stockpile as a first line of defense until a vaccine can be developed.

Also, Senator Bill Frist weighs in. A key quote from his Op-Ed:

(HT: Avian Flu – What We Need to Know)

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