Pandemic Flu

[mugwump]

The Institute of Medicine/National Academy of Science released a letter report on H5N1 pandemic modeling that highlights some of the questions asked here.

Basic inputs into any pandemic model are the infectivity rate (how many catch it), the attack rate (how many who are infected get sick), the mode of infection (aerosols, surface contamination, food, etc), mean time between cases (elapsed time between on infection and the ones produced by it), and mean transmission rate (related to infectivity rate: how often will an infection be passed on).

Please note I'm going quickly here and these terms have nuanced definitions that sometimes escape me, but the gist is this: we don't know much of anything about these critical inputs when it comes to flu in general and H5N1 in particular.

"All models lie, some models are useful." So are the models useless? Well, are mortars useful? It's an apt analogy. By plugging in a range of assumptions, these guys can bracket the problem with best case and worst case. As more data come in, they correct the model and fire another round. The time lapse between corrections can be frustrating, but at least the models help clarify what we don't know (questions are sometimes more important than answers).

On first reading, some of the models support quarantine, masks, respiratory etiquette, etc. as useful in "flattening the curve", the current mantra in public health circles.

I do know for a fact that a couple of these guys have prepped for 3 months of total isolation. ("Food: check; water: check, pocket protectors: check...")

[jasonglh]

Interesting first person account from one of the survivors of the 1918 Flu pandemic:

Link

The city began shutting down. The federal government staggered its hours to limit crowding on the streets and on streetcars. Commissioners overseeing the district closed schools in early October, along with playgrounds, theaters, vaudeville houses and "all places of amusement." Dances and other social gatherings were banned.

The commissioners asked clergy to cancel church services because the pandemic was threatening the "machinery of the federal government," The Washington Star newspaper reported at the time. Pastors protested.

I wonder how America would react to such restrictions in 2007?

[The Reaper]

Originally Posted by jasonglh

Interesting first person account from one of the survivors of the 1918 Flu pandemic:

Link

I wonder how America would react to such restrictions in 2007?

Natural selection.

Those who ignore it can die, and then traffic should be much easier for the rest of us.

TR

[jasonglh]

From the tail end of this article

The president also signed a bill to create a new agency within the Health and Human Services Department to oversee the development of medicine and equipment to respond to a bird flu pandemic or a bioterrorism attack.

"It will increase our preparedness and response capabilities for public health emergencies by increasing our medical surge capacity, strengthening our public health infrastructure, and clarifying the responsibilities of federal officials," Sen. Edward Kennedy

A bit of what the bill does is here:

Linky


I love the last bit:

The bill does not identify any likely technology candidates for the new disease outbreak network, but critics call current HHS disease surveillance systems under management of the Centers for Disease Control and Prevention a “money pit.” They say the systems lag behind CNN news reports in real-time monitoring of disease outbreaks.

Sounds like the Brits have their act together on this already. The bill gives the Department of Health and Human Services two years to build a network that would detect catastrophic disease outbreaks. I hope we have 2 years. :blink:

[InTheBlack]

Came across a "family pack" of N95 mask & stuff that includes goggles.

Kinda makes sense; your tear ducts allow entry to your nose...

[InTheBlack]

I think the article has serious flaws in its premise. Its no surprise that the rich have a lower chance of dying, from any cause. To say that overall death rates will be lower because income is higher is just wrong. The disparity between high and low income is probably greater in 2006 than it was in 1918, which means that the lower end will have relatively LESS access to scarce medical resources than in 1918.

The H5N1 pandemic might cause economic collapse by breaking the "just in time" supply chain.

Deaths occurring from the social upheaval need to be counted as well as direct infection fatalities.

Sorry I don't have the URL:
>>>
World Death Toll Of a Flu Pandemic Would Be 62 Million
Study Examined 1918-19 Outbreak

By David Brown
Washington Post Staff Writer
Friday, December 22, 2006; A03

snip

The extra deaths ranged from 0.2 percent of the population in Denmark to 7.8 percent in the Central Provinces and Berar region of India -- a 39-fold difference.
snip

If a modern Spanish flu killed all its victims in one year, it would more than double global mortality. About 59 million people now die each year.

snip

Murray and his colleagues analyzed the death patterns and deduced that about half the variation from region to region was explained by differences in per capita income. For every 10 percent increase in income, a person's risk of dying during the pandemic fell 10 percent.

Why the poor were so vulnerable is unknown. It could have been that many were already ill with parasites or other illnesses or lacked micronutrients such as Vitamin A and zinc that are essential to immunity.

To estimate the effects of a modern Spanish flu, the researchers applied the 1918-1920 death rates to the current world population broken down by income, sex and age. They came up with a range of 51 million to 81 million deaths, with a median of 62 million.

Even though the world's population is three times what it was during the Spanish flu pandemic, the estimated mortality of a modern Spanish flu isn't three times what it was in 1918. That is mainly because per capita income is higher now -- and the higher the income, the lower the risk of dying of influenza.

The illness caused by the 1918 virus was largely untreatable. There were no antiviral drugs, no mechanical ventilators to help people breathe and no antibiotics to treat bacterial pneumonias that often set in after the viral infection. All are available now and would reduce the death toll, though some interventions would be in sort supply during a pandemic.

[mugwump]

Originally Posted by InTheBlack

I think the article has serious flaws in its premise...

Well, it is what it is, a statistical analysis of death rates from three periods: 1) the three years prior to the 1918-1919 pandemic years, 2) 1918 and 1919, and 3) the three years after the pandemic. The report is good at analyzing the inputs it uses -- my problem is with the inputs and the context, the "smell test."

Let's just look what the report says. If a pandemic hit and the outcome was as predicted in the article, it would be no walk in the park. Doubling the excess death rate over two years (as the paper predicts) glosses over the fact that the excess deaths would occur in waves, with each wave producing eight time to ten times the normal death rate in a region. It might average out as a 200% increase, but a 1000% increase in each of three 4-week spans would be devastating economically and psychologically.

That most deaths would occur in the third world and southern latitudes is no surprise. We don't need statistical predictions, the history of the 1918 pandemic tells us that. At the very beginning of this thread I cited reports from India that indicate up to a 10% excess death rate -- staggering.

The smell test: The paper tries to present what might happen to the world if a "Spanish Flu" pandemic hit us now, and they come up with 51 to 81 million excess deaths. In 1918 there were 12 cities with a population of 1 million and today there are over 500. Over a billion people now live in cities and are classed by the UN as living below the poverty line. The total world population is over 3 times higher now.

So, some facts: 1) the consensus figure for excess deaths from flu in 1918-19 was 100 million deaths 2) population has tripled since then 3) the vast majority of that population growth is in the demographic group the paper cites as the most at risk: southern latitudes and living below the poverty line 4) much of this increased population lives packed together in high-density cities. Given all this, how do they predict 51M to 81M deaths?

Assuming no antivirals, primary medical care, or vaccine for the vast majority of the world's population (a safe bet) my back-of-the-envelope calculations come up with 300M deaths, assuming no change in mortality from 1918 (not a safe bet) and no massive die-off in AIDS patients (not a safe bet).

Now throw in social/infrastructure effects.

I think the best course is to just not have a pandemic.

[jasonglh]

In ICU we have a cross training relationship with ER so back in early Nov I spent the better part of a day working the triage desk of our ER. I would wager 50% of the patients that came in wrote flu like symptoms on the triage slip. Now non of these idiots actually had the flu but they wanted to get something to fix it none the less. I remember thinking that day that if there were a pandemic or the deadly avian flu we would need the riot police to maintain order outside the ER. Can you imagine the ignorant masses lined up outside scared to death by the media demanding the Tami flu we probably wont have? Maybe I just have little faith in the general public but I am having visions of the villagers with torches banging on the gates of Dr Frankensteins castle.

[mugwump]

We had a knifing at the local Best Buy over the last Playstation 3 when it was first launched. I don't know what it'll be like when they believe their lives are on the line, but it can't be good.

[The Reaper]

Promising, if we avoid the pandemic till it is ready.

TR

http://www.dailymail.co.uk/pages/liv...n_page_id=1774

The vaccine to cure every strain of flu
by FIONA MacRAE

Last updated at 22:20pm on 28th December 2006

Join the debate » British scientists are on the verge of producing a revolutionary flu vaccine that works against all major types of the disease.

Described as the 'holy grail' of flu vaccines, it would protect against all strains of influenza A - the virus behind both bird flu and the nastiest outbreaks of winter flu.

Just a couple of injections could give long-lasting immunity - unlike the current vaccine which has to be given every year.

The brainchild of scientists at Cambridge biotech firm Acambis, working with Belgian researchers, the vaccine will be tested on humans for the first time in the next few months.

A similar universal flu vaccine, being developed by Swiss vaccine firm Cytos Biotechnology, could also be tested on people in 2007 - and the vaccines on the market in around five years.

Importantly, the vaccines would also be quicker and easier to make than the traditional jabs, meaning vast quantities could be stockpiled against a global outbreak of bird flu.

Martin Bachmann, of Cytos, said: "You could really stockpile it. In the case of a pandemic, that would be a huge advantage.

"If you were to start making a traditional vaccine at the start of a pandemic, there is no way there would be enough."

The Government believes a bird flu pandemic is inevitable, killing 50,000 people in Britain alone.

However, it acknowledges that the bug could be much more lethal - infecting one in two people and claiming more than 700,000 lives.

Normal winter flu can also kill, claiming up to 12,000 lives a year in the UK.

Although a vaccine exists, constant changes in the virus's appearance have until now made it impossible to create just one flu vaccine. Instead a new vaccine is put together each year to protect against the particular strains circulating at that time.

In addition, the virus used in the jab is grown in hen's eggs - a time-consuming process that yields just one shot of vaccine per egg.

The new jabs would be grown in huge vats of bacterial 'soup', with just two pints of liquid providing 10,000 doses of vaccine.

Current flu vaccines focus on two proteins on the surface of the virus. However, these constantly mutate in a bid to fool the immune system, making it impossible for vaccine manufacturers to keep up with the creation of each new strain.

The universal vaccines focus on a different protein called M2, which has barely changed during the last 100 years.

The protein is found in all types of Influenza A, including the current bird flu and the virus that caused the 1918 Spanish flu pandemic which killed up to 50 million across the globe.

Normally, such vaccines would have to go through at least five years of human tests before going on the market. However, if a bird flu pandemic occurs before that, they could be made more quickly available.

Zurich-based Cytos, which is also developing anti-smoking and obesity vaccines, has showed that its version of the jab stops mice dying from a dose of flu strong enough to kill them four-times over.

The vaccinated animals were also spared the fever that normally goes along with flu.

Although it is too early to say what the effect would be in humans, an initial course of two or three shots could provide long-lasting immunity, topped up with booster shots given every five to ten years.

Dr Ashley Birkett, of Acambis, said: "It wouldn't be that one shot protects for life but you would need fewer doses over your lifetime."

In addition, the jabs could be produced in vast quantities and stockpiled ahead of a flu pandemic - or even given to people in advance.

In contrast, a traditionally-produced vaccine, matched to the specific strain of flu, would not be available until around six months after the start of the pandemic.

The new vaccines only protect against influenza A - the version of the bug responsible for pandemic flu and the most severe cases of winter flu.

However, it may also be possible to create a similar jab against influenza B, which causes a milder form of winter flu.

Professor John Oxford, Britain's leading flu expert, said the development of a universal vaccine was the "holy grail" of flu research.

He added: "If you get a M2 vaccine which protects against the whole caboodle in the same vaccine, the possibilities are huge."

But, others cautioned that there is no guarantee that the jabs would be as effective in humans as it has been in animals.

Virologist Professor Ian Jones, of the University of Reading, said: "It is an encouraging technique which may have a role to play but it is too soon to assume that it will translate into a universal vaccine in the human population."

Dr Jim Robertson, a vaccine expert from the government-funded National Institute for Biological Standards and Control, said the main advantage of a universal jab would be lasting immunity.

"If it works, it will be lovely," he said. "The best result would be that it would last for a long, long time."

Dr Ron Cutler, an infectious diseases expert from the University of East London, said: "Continual protection would be a tremendous advantage against flu."

He cautioned however, that there is no guarantee that the M2 protein will not mutate in the future - meaning the jab will have to be regularly reformulated.

[mugwump]

Things are still chugging along -- heavy avian activity and several human clusters in SE Asia and N Africa -- but still no truly alarming trends.

There's a suspected six-patient cluster of family members plus neighbors in Indonesia. The index case is the 14 year-old boy reported in the MSM. The following is Toggletexted from an local source (cite):

Six patients are currently treated in the Friendship Hospital, Jakarta East, till Monday (8/1).

They experienced the sign of the deadly illness.

The six patients generally still have relatives's relations.

Ramli was treated three days set after being stated positive contracted bird flu.

Followed by the mother, the brother, as well as his three neighbours, this morning.They lived in the Rawabebek region, Angke, Jakarta North.

Avian H5N1 is exploding across flocks in southern Viet Nam and there are additional reports coming out of Egypt and Nigeria. South Korea has gotten close to eradicating avian flu after truly draconian culls of poultry, swine and dogs, but still no cigar.

The report we were discussing here around 20ish of December that predicted 20-100 million deaths has been pretty roundly slagged as wildly optimistic. This is fairly representative:

The number of people that could die in a flu pandemic that matches the 1918-20 outbreak will be "very scary" and far higher than the 62 million deaths forecast by a recent study, an adviser to the White House said on Monday.

"I think that number is a very optimistic number if we are talking about a 1918-wide pandemic today," Rajeev Venkayya, Special Assistant for Biodefense to President Bush

There were two small clusters late in December in S Viet Nam and Egypt which are widely believed to have been falsely declared negative. NAMRU-3 is reportedly developing a new diagnostic test to detect mutated strains in Egypt.

[mugwump]

This is no more than was reported here yesterday, but it's interesting that the NYT appears to be Toggletext'ing local reports, or grazing through blogs and forums to get their news. [cite]

A new human cluster of avian flu cases could be emerging in a suburb of the capital, Jakarta, according to Indonesian news reports. One case of H5N1 flu, the country’s 75th, was confirmed by the Health Ministry over the weekend; it was in a 14-year-old boy who had reportedly buried a flock of backyard ducks that died suddenly. He was alive but using a respirator to breathe. A local radio station and news outlets said six other people from the same town — at least three of them related to him — were hospitalized with flu symptoms in Jakarta, being treated with Tamiflu and awaiting test results. Indonesia has failed to get its poultry epidemic under control since it emerged in 2005.

[mugwump]

It looks like Japan has poultry H5N1 for the first time in three years. Korea still can't stamp out its infections. Avian H5N1 has exploded across the Mekong delta in VN and the first human infection has been reported there. More than 70% of all tested chickens in China have asymptomatic H5N1 (due to shoddy vaccine use). I heard from a guy who knows a guy in Nigeria who says hundreds of flocks in southern Nigeria are having die-offs, although only one flock is officially reported. Not really news, but the take-home is that this virus is endemic throughout Asia and Africa and will never be eradicated.

On the human front there are reports of three clusters around Jakarta, with six teens admitted with severe respiratory distress and bloody sputum, but no test confirmation, today. NAMRU-3 released the sequences for the Nile delta cluster in Dec '06 and there are mutations considered "disquieting." The Qinghai isolates there appear to have "fixed" another mutation needed for the virus to go pandemic in humans (maybe, maybe not, see next paragraph) and have picked up another mutation that makes it more similar to H3 and type B influenzas, both highly transmissable in humans.

A new paper in Nature casts doubt on the whole alpha-2 / alpha-6 sialic acid receptor theory. That's the one where they say birds have receptors in their guts and humans scattered only deeply in the lungs, which is why H5N1 is poorly transmitted in humans. Turns out that's all crap, humans have oodles of receptors high in the respiratory tract (nose, throat) for H5N1 and massive quantities of viruses are shed from there in human infections. Something else is going on to prevent efficient transmission. Turns out we don't know very much about this virus at all.

The bad news from the Nature article is the implication that all aerosols, including the largest, would be infective if the final mutations are picked up. The bet 'til now was that only the tiniest aerosols could make it deep into the lung where the receptors were thought to be. It's still thought that that flu viruses are expelled most efficiently in those larger droplets you've seen in the famous "sneeze" photographs. Those droplets tend to get caught in the nose, where we now know we have many H5N1 receptors. Bad juju.

Note to self: buy more masks.

ETA the Nature cite: Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract

[mugwump]

Niman's web site is reporting 20 suspect cases in and around Jakarta, discusses the NAMRU-3 findings in the Nile delta cluster viruses, and apparently corroborates the Nigeria avian flu explosion rumor.

http://www.recombinomics.com/News/01...Jakarta_3.html

http://www.recombinomics.com/News/01...ia_Spread.html

Take everything (including my posts) with a grain of salt -- Niman once declared the pandemic had started in 2005 -- but he's generally ahead of the curve. He peruses the blogs and local news sources and posts useful summaries. He's a very good scientist as well -- you can tell by how many people he pisses off when he's right.

[mugwump]

Something has changed in the situation in Indonesia.

There are currently over 30 suspect human H5N1 cases per local media reports and there have been two additional deaths since 00:00 13Jan2007 local time. Clusters of up to seven family members are reported. So far the old pattern of family clusters appear to be holding and there is no evidence of human-to-human transmission up to this point. There are reports of symptoms suggestive of cytokine storm (ARDS, profuse hemorrhaging, bloody vomitus, death) along with unusually shortened incubation period and relatively short time from initial symptoms to death.

Possible explanations for the sudden spike in cases are a large increase in poultry infections (meaning more opportunities for bird-to-human contact and B2H transmission) or a mutation in the virus that makes B2H transmission more efficient. This is pure speculation on my part, by I'd vote for the mutation. There has been no culling in Indo and no effective controls have been put in place to mitigate poultry infections, so my thinking is that every "tail of poultry" (as they call them in Indo) that can be infected, already was by the beginning of 2006.

The point of concern here is not the current number of B2H (if that's truly the mode of infection) infections per se, but the opportunity that each human infection presents for this virus to further mutate in a way to allow efficient H2H transmission. Each human case is a mixing vessel that can allow recombination with other flu types the patient might be co-infected with.

Although there is a health care worker currently suspected of having H5N1, he is part of a 7-member family cluster and is not currently suspected of having contracted the infection via H2H (although he is the index case in the cluster, apparently, so who knows). There are no reports other HCWs infected, nor of social disruption typical in ongoing pandemics (refusal to transport patients to hospital, shunning of families of patients, etc.) and the infections, as I said earlier, seem to be confined to smallish clusters among family members.

No one knows where this will lead, and it's still entirely possible that there is some species barrier in this virus that will prevent it from breaking out. That said, NAMRU-3 in Egypt has recently seen some scary mutations in human cases there, and I wouldn't rule out NAMRU-2 in Jakarta reporting something similar as well.

Given the recent simulations that suggest "sheltering-in-place" (voluntary complete quarantine) and strict travel controls could flatten the curve of infection rate, I think it would be prudent to review your plans for pulling family members home just in case. I suspect the feds might quickly impose some fairly draconian travel restrictions if things break out.