November 29, 2004
Next Influenza Pandemic Will Kill Millions

Shigeru Omi of the World Health Organization says we are overdue for the next big flu pandemic.

"I believe we are closer now to a pandemic than at any time in recent years," said Shigeru Omi, regional director for the Western Region of the World Health Organization (WHO).

"No country will be spared once it becomes pandemic," he told a news conference on Friday.

"History has taught us that influenza pandemics occur on a regular cycle, with one appearing every 20 to 30 years. On this basis, the next one is overdue.

"We believe a pandemic is highly likely unless intensified international efforts are made to take control of the situation,"

Southeast Asian farming practices make mixing of influenza viruses across species much more likely.

Chickens, ducks and other animals are often allowed to roam freely on small Southeast Asian farms, and often come into close contact with wild animals and with family members.

Some animal health experts have been promoting so-called "closed-system farming," in which poultry are raised in a sealed environment where they face minimal exposure to outside infections. But the system is likely to be prohibitively expensive for many poor farmers.

One worrisome development is the spread of the H5N1 virus into more species in Southeast Asia. The thinking is that this spread gives the virus greater opportunity to coinfect a pig that also has a human-compatible flu infection so that the two viruses can exchange genetic code and produce a lethal virus that is human-compatible.

Klaus Stohr says the next pandemic is a matter of when, not if.

"There is no doubt there will be another pandemic," Klaus Stohr of the WHO Global Influenza Program said on the sidelines of a regional bird flu meeting in Bangkok, Thailand.

"Even with the best case scenario, the most optimistic scenario, the pandemic will cause a public health emergency with estimates which will put the number of deaths in the range of two and seven million," he said.

Note that the 7 million deaths figure assumes a less lethal virus. A more lethal virus with a potency similar to the 1918 outbreak could kill tens of millions.

Stohr says there is insufficient global vaccine production capacity.

The world's total capacity for flu vaccine now is only 300 million doses, and it would take at least six months to develop a new vaccine to fight a pandemic. The WHO wants to get "all issues on the table," monetary and scientific, that prevent getting more vaccine more quickly, he said.

...

The United States is the only nation that has commissioned work on potential pandemic bird flu vaccines, Stohr noted. The National Institutes of Health has given Aventis Pasteur and Chiron Corp. contracts to produce prototype bird flu vaccines that are expected to be ready for human tests late this year.

While strain H5N1 is the main fear strains H9N2 and H7N7 have also broken through to human populations and killed small numbers of people in recent years. So we can not be certain which strain to target.

A pandemic bird flu virus would require two vaccine shots for adequate protection.

A pandemic vaccine would need to protect against only one strain of flu virus -- the newly emerged one -- rather than three strains, as is the case with the annual flu shot. However, because nobody on Earth would have underlying immunity to the new strain, people would need to get two shots to be protected.

This means that there is only enough capacity to produce vaccine for about 150 million people. However, there is reason to hope that intradermal (rather than the standard intramuscular) delivery of standard flu vaccine would allow only one fifth of a normal dose to be used in place of the standard full dose. A new paper just out in the New England Journal of Medicine, "Dose Sparing with Intradermal Injection of Influenza Vaccine", found that intradermal injection allows vaccine doses to go 5 times as far in young adults.

Results Subjects who received an intradermal injection with one fifth the standard dose of influenza vaccine had increases in the geometric mean HAI titer by a factor of 15.2 for the H1N1 strain in the vaccine, 19.0 for the H3N2 strain, and 12.4 for the B strain on day 21, as compared with respective increases by a factor of 14.9, 7.1, and 15.3 for the intramuscular injection of the standard dose. Seroconversion and seroprotection rates were similar in the two groups on day 21, ranging from 66 to 82 percent and 84 to 100 percent, respectively. Local reactions were significantly more frequent among recipients of intradermal injections than among recipients of intramuscular injections, but such reactions were mild and transient.

One worrisome note on this study: If doctors start to routinely use fractional doses of flu vaccines then that will reduce the demand for flu vaccine production and that, in turn, will lead to a reduced capacity to make influenza vaccine. Then we will approach a pandemic with no more effective production capacity than we have now.

Not only is vaccine production capacity limited but also it takes 6 months to develop and manufacture a new strain of flu vaccine.

Klaus Stohr says the vaccine production period can be shortened by advanced preparation but he is assuming that he knows which strain to target.

"It will take six to eight months before a company has all the paperwork done and the testing [to get the vaccine licensed]," he said.

"That can be shortened to perhaps two to three months if the paperwork and testing is done now.

The lag time for producing vaccine is a problem that needs to be solved by the development of a new method for producing vaccine. The use of fertile chicken eggs to grow vaccine is the biggest bottleneck. The development of a better method for producing vaccine would also likely result in a more rapidly scalable production technology as well. The development of the ability to grow vaccine in cell culture would allow faster scaling in part because cells can be grown much more rapidly than fertilized egg production can be scaled up.

The vaccine production problem is not going to get solved any time soon. This argues for the need to look at other ways to respond to a new flu strain which has pandemic potential. Methods to slow the rate of spread of a dangerous flu are needed. Far better methods could be developed to slow the speed of spread of an outbreak and many of these methods could be very low tech and cheap.

For example, children are major spreaders of influenza in schools. Well, how could schools be managed (short of shutting them down which would be very effective but a large burden to working parents) to reduce the spread of diseases? Here is one idea: Imagine transparent plastic dividers between aisles of chairs so that cough spray could not travel between rows and kids could not as easily touch each other. This could be extended to dividers between rows with some sort of ceiling contraption for raising the plastic dividers like blinds are raised. It is a cheap response. But this response requires lead time for buying and installing the dividers. So this would best be done before a pandemic flu strain emerged.

Another idea: conduct more studies on how influenza virus spreads. What percentage of flu spread happens through airbone droplets versus physical contact between people versus touching of contaminated surfaces? What locations (types of occupations, schools, etc) are where most flu cases are spread? The public should be supplied with excellent information at the start of an outbreak so that living patterns and daily routines can be adjusted to reduce risk of transmission.

Some adjustments to reduce transmission risk are pretty obvious. People could go shopping later at night to reduce the number people in a store at any one time. Businesses could allow more people to work at home or to work at off hours. Better filtration systems could be installed in buildings to remove airborne particles from the air more rapidly. Public places could require covering of mouths and noses to reduce the discharge of cough particles into the air.

Share |      Randall Parker, 2004 November 29 11:19 AM  Dangers Natural Bio


Comments
Robert Silvetz said at November 29, 2004 1:54 PM:

Question: Am I correct in inferring that we are between 3 and 4 cycles overdue for a pandemic?

And if that's the case... why have we not seen a pandemic? And would the forces, whatever they may be, that have prevented pandemics for 3 to 4 cycles not continue?

The last 100 years, are different, from from what has gone before... World Wars, intermingling of populations, worldwide air travel and commerce, sanitation etc etc etc.

Thoughts?

Randall Parker said at November 29, 2004 2:07 PM:

Robert,

The argument has been made that the overdue pandemic has been averted by massive kill-offs of infected chickens, isolation of humans infected by very deadly influenza strains, and other public health measures. In other words, virus strains that would have caused pandemics have been prevented from doing so. This argument seems plausible to me.

Suppose that is the case. Will it continue to be the case?

In the longer run as Southeast Asia industrializes that will cause changes in farming practices to make farming practices more like US practices. This will reduce the ability of viruses to hop between species. But at the same time, air travel makes it easier for a pathogen to quickly travel large distances and spread rapidly. Of course also at the same time we have advances in diagnosis and treatment, vaccines, public health tracking with computers, and other technological advantages. So one should not expect old historical cycles to continue.

Therefore you bring up a very valid point. But does that mean the next pandemic will continue to be avoided? We will find out for certain in the fullness of time.

Tman said at November 29, 2004 3:02 PM:

Randall,


In light of the point made by Robert, I have a question for you- which is a more immediate and pressing danger- asteroid/NEO strike or flu pandemic?

Randall Parker said at November 29, 2004 3:27 PM:

Tman,

I think it is hard to calculate probabilities on either a kiler asteriod or a killer influenza. I haven't posted on this yet but I recently came across a paper that provides evidence for a lower risk from asteroid impacts than has previously been believed. See this paper.

Regionally destructive collisions with impact energy greater than 4×1018 J (~200 m diameter) strike the Earth every 56,000±6000 yr. Collisions in the range of the Tunguska event (4–8×1016 J) occur every 2000–3000 yr. These values represent the average time between randomly spaced impacts; actual impacts could occur more or less closely spaced solely by chance. As a verification of these impact rates, the crater production function of Shoemaker et al. (1990, Geological Society of American Special Paper 247) has been updated by combining this new population model with a crater formation model to find that the observed crater production function on both the Earth and Moon agrees with the rate of crater production expected from the current population of NEOs.

Previously some group had argued that the risk of a Tunguska impact at around once every 400 years. Which claim is more accurate? Heck if I know.

A new NASA infrared telescope to be launched in 2008 may find as many as 100,000 additional asteroids. Though it is not clear how quickly it will find them since the telescope will also be used for looking at very distant objects. Since a significant portion fo the $208 million cost for that project will be one-off NRE costs it would be a lot cheaper to build a second one and dedicate it to looking for asteroids.

fly said at November 29, 2004 4:45 PM:

Re: Why no recent pandemics? My guesses.

Healthier food preparation standards and technology.
Better average health and nutrition of the world population.
Quicker response to detect and isolate infectious diseases.


Re: Technology to hinder disease transmission.

Public doorknobs, faucets, and buttons should be coated with antibiotic materials or operate without touching.

Virus proof masks should be stockpiled and made freely available during epidemics.


Re: Future technology.

Fast response to create a vaccine and quick means to scale up vaccine production.

A broad-spectrum drug that targets critical viral metabolic pathways.

Immune system enhancements that significantly improve the body’s ability to fight off infection.

Richard said at November 30, 2004 8:44 AM:

As to spreading in schools,

Pretty well impractical as many, if not most, desks in schools are moveable so they can form circles and squares. Putting them in line and making partitions would take a financial and cultural effort that people will probably not care to make until they are dropping like flies.

It is not just Grades 1 through 12. Kids in preschool through kindergarten are always on the rug, in story circle and playing together. Kids from six weeks through grade 6, at least are in daycare, a very septic environment. You think Heather and Caitlin
(or their spouses) are going to give up their meaningful jobs as branch manager to stay at home? They probably can't because of a mortgage.

Engineer-Poet said at November 30, 2004 9:32 PM:

I was going to suggest a relatively simple and cheap regimen of dust masks impregnated with anti-virals (you could make your own masks with a spray bottle of anti-viral stuff, like the zinc that kills rhinoviruses) and gloves; if people don't transfer stuff to each other it's much harder for the virus to spread.

And then you reminded me of kids.  They monkey-wrench the whole idea (appropriate for monkeys ;-).  Isolating them from each other is probably impossible, but is there any way that we could isolate e.g. classroom groups from each other?

There might be a legal way around the mortgage issue; it's certainly going to be cheaper to pay for people to stay home than to bury even a small fraction of the population, and having the framework to do this ahead of the pandemic so that prophylaxis and quarantine can work would pay huge dividends.

Randall Parker said at November 30, 2004 10:33 PM:

E-P,

Yes, kids strike me as the hardest problem.

But think like an engineer. We can't create a perfect design. But anything that will improve things on the margins will reduce the spread of the disease. Kids will end up coming into some contact with each other. But how to reduce it?

A few ideas off the top of my head:

1) Have different grades or classes come in on different days and times of days. Just plain reduce the number of kids in a school each day.

2) The plastic partitioning that I've already suggested. Though on reflection I see problems with the kids seeing the blackboard. What they need is a mini-electronic blackboard per aisle. Or per seat.

3) Require them to wear gloves.

4) Give them masks that are full face masks perhaps with Halloween appearances. The unique appearances would make it easier to tell them apart. The masks could even have their names on their foreheds. Remember touching of hand to face is one way that viruses get into bodies.

5) Portable air filter systems in each class to remove airborne particles rapidly. Though there'd likely be a shortage of such items perhaps they could be build from fans and the appropriate kinds of cloth? Remember, large particle removal would be better than no particle removal. Though perhaps air circulation increase in the room would be worse and it would be better to let cough particles drop to the floor.

6) Make kids each lunch in classrooms. That way they do not all come together in the cafeteria. The cafeteria could make sandwiches and other simple food for distribution.

7) Add porta-potties to school grounds and assign them by classroom. That way germs couldn't travel between classrooms.

8) Stagger trips out to the playground. Cut back on the length of playground period. Make kids in the playground stay separated by classroom.

9) Use smaller and more busses to reduce the number of kids exposed to each other during transportation.

Engineer-Poet said at December 1, 2004 4:09 AM:

My off-the-cuff appraisal:


  1. This effectively puts parents on part-time work schedules, without completely isolating the kids.  This might be worse than doing nothing, imposing costs without yielding much if any protection.
  2. Two words:  fire code.
  3. I can't see second-graders keeping gloves on all the time, let alone preschoolers, but trials wouldn't be all that expensive to run.  Using rhinoviruses as a proxy for flu would let us check the efficacy.
  4. Clear plastic masks with anti-viral gauze filter elements.
  5. You can't give each seat a separate sanitized air flow, so you might as well forget it.
  6. Health code may prohibit this; do you want to deal with vermin problems in the whole school, or have people eating in biology lab, chemistry lab or the shop rooms?
  7. Having children outside the building except for recess would be a problem.  Probably easier to have antibacterial UV lights in bathrooms which are triggered off by motion sensors, though expense would still be a big issue.
  8. That might work, but you'd need to mandate gloves to reduce transmission via playground equipment.
  9. Purchasing buses and hiring drivers would be next to impossible.  This looks like a non-starter.

Richard said at December 1, 2004 5:48 AM:

I don't know how many of you have kids or deal with the school system, but as a home schooling father who took his kid out of the system because of the sheer silliness of it, getting anything done that represents real progress is well nigh impossible. Look at the forces at work:

Teacher's unions-my dad was a union man and his union did a good job at its task, getting more money for less work. Okay at the phone company, disaster at the public school.

Parents-In truth, they look at school as daycare and want their kids to be entertained. They have no idea what education is.

School Committees-they may go along, as spending money is what they do, but they will have no conception of why or how so anything can be slipped by them for good or ill.

The students themselves-it may have been decades ago, but I as a non scholar (though avid reader of history, so kind of an honorary nerd) remember it well. Other than a nerdy few, almost all kids are there to socialize with each other. They are going to stay in their little partioned rows only if manacled (not a bad idea for some of them).

Don't even think about college students. For most of them, it is just advanced daycare. Does one really think that an announcement by an assistant dean of an inpending pandemic is going to bring about a drop in the number of keggers.

Of course after the infirmaries start to fill up, folks will be willing to put up with anything. If you really think the pandemic is coming soon, invest in bubble suits to be sold on tv. It does not matter if they are effective, you will be set for life, if you live through the crisis.

Patri Friedman said at December 1, 2004 9:50 PM:

I consider the WHO a rather unreliable source. The WHO exists to combat global diseases. Therefore they have an incentive to greatly exaggerate the threat of global diseases. (Just like Homeland Security dept. and terrorism, or the CDC and domestic infectious disease). Look at the ridiculous fuss they made about SARS, which killed less people in its months-long run than the flu or TB or malaria kill every few days.

Patrick said at December 2, 2004 12:38 AM:

As someone who works in infection control engineering, I'll step right in here.

1. The most effective way of reducing disease spread, even of lung type diseases like SARS, is getting people to wash their hands. Simple changes to public toilet layouts make big differences in terms of population rates of infection.
eg. Toilet doors should open out. That way you dont need to grab the handle to leave, thus reinfecting your clean hands. Most toilets are designed otherwise for reasons that never stand up to scruitiny. This costs NOTHING to implement for new toilets, and maybe 20 minutes to change for existing toilets.
Toilet wash basins should have self turning off taps, so you don't need to touch the taps after washing.
Never use cloth towels, use disposable paper or hot air.
Have more washbasins, with clean, full soap dispensers.


2.Public transport is bad mmmkay? At least as far as infection control is concerned. A bus or crowded train is a real hotspot. Not much you can do about this, it isn't so much the unit size as the crowding.

3. Childcare is bad too. Once again, not so many simple solutions. Maybe if childcare involved more running around in a sportsfield and less rolling around on the floor. If kids bring food from home rather than the American style of it being supplied in a cafeterria, then that removes one source of spreading.

4.Open the windows and get some fresh air. This may be an issue in cold countries.

5.Once people get scared, masks ARE easy to implement, but they are mainly to stop YOUR germs from being coughed and sneezed into the air, rather than protect you from other people's germs. Gloves are more successful in protecting yourself.

Randall Parker said at December 2, 2004 11:34 AM:

Pat,

1) Are there any devices that can be used to quickly clean the hands of a few hundred kids in a grade school? I picture them all coming off the bus heading into class. Are liquid antiseptic gel dispensers in each classroom the best way to go?

2) How to make public transport less bad?

3) Are there types of materials for gloves that make it hard for germs to survive on their outer surfaces?

Randall Parker said at December 3, 2004 10:01 PM:

E-P,

Yes, kids strike me as the hardest problem.

We can't create a perfect design. But anything that will improve things on the margins will reduce the spread of the disease. Kids will end up coming into some contact with each other. But how to reduce it?

A few more ideas off the top of my head:

1) Have different grades or classes come in on different days and times of days. Just plain reduce the number of kids in a school each day.

2) The plastic partitioning that I've already suggested. Though on reflection I see problems with the kids seeing the blackboard. What they need is a mini-electronic blackboard per aisle. Or per seat.

3) Require them to wear gloves.

4) Give them masks that are full face masks perhaps with Halloween appearances. The unique appearances would make it easier to tell them apart. The masks could even have their names on their foreheds. Remember touching of hand to face is one way that viruses get into bodies.

5) Portable air filter systems in each class to remove airborne particles rapidly. Though there'd likely be a shortage of such items perhaps they could be build from fans and the appropriate kinds of cloth? Remember, large particle removal would be better than no particle removal. Though perhaps air circulation increase in the room would be worse and it would be better to let cough particles drop to the floor.

6) Make kids each lunch in classrooms. That way they do not all come together in the cafeteria. The cafeteria could make sandwiches and other simple food for distribution.

7) Add porta-potties to school grounds and assign them by classroom. That way germs couldn't travel between classrooms.

8) Stagger trips out to the playground. Cut back on the length of playground period. Make kids in the playground stay separated by classroom.

9) Use smaller and more busses to reduce the number of kids exposed to each other during transportation.

Tj Green said at December 5, 2004 4:43 PM:

Communication is a powerful weapon against disease.When the AIDS virus was discovered,the response,in the west,was instantaneous.Our world seems to be changing,it works together to defeat harmful pathogens.The bird flu had evolved human to human transmission.Health workers are doing a remarkable job of containment.They are risking their lives to save ours,shouldn`t we be protecting them,by developing better vaccines?

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