2007 February 03 Saturday
2 Mutations Made 1918 Pandemic Dangerous

Two amino acid changes in a surface binding protein are enough to make yjr 2928 killer pandemic strain of influenza hard to transmit.

Experts at the Centers for Disease Control and Prevention have shown that a molecular change in the 1918 pandemic influenza virus stops its transmission in ferrets that were in close proximity, shedding light on the properties that allowed the 1918 pandemic virus to spread so quickly and potentially providing important clues that could help scientists assess emerging influenza viruses, such as H5N1.

The study, which is published in the Feb. 5 issue of Science, showed that a modest change of two amino acids in the main protein found on the surface of the 1918 virus did not change the virus's ability to cause disease, but stopped respiratory droplet transmission of the virus between ferrets placed in close proximity. The experiments were conducted with ferrets because their reaction to influenza viruses closely mimics how the disease affects humans.

The 1918 influenza strain killed tens of millons of people. The interest in studying the 1918 strain is driven in part by fear that the avian flu H5N1 might mutate to cause a similar big killer human pandemic.

But do not panic. This result does not mean that H5N1 bird flu is only 2 mutations away from causing a massive human pandemic. Bird flu probably has additional mutations that make it more suited to spead in birds than in humans.

To spread and cause illness, the influenza virus must first bind to host cells found in humans and animals. The Science study suggests that the hemagglutinin (HA), a type of protein found on the surface of influenza viruses, plays an important role in the 1918 virus's ability to transmit from one host to another efficiently. This research suggests that, for an influenza virus to spread efficiently, the virus's HA must prefer attaching to cells that are found predominately in the human upper airway instead of cells found predominately in the gastrointestinal tracts of birds. Other changes may be necessary as well. Current H5N1 viruses prefer attaching to avian cells, suggesting the virus would need to make genetic changes before it could pass easily between humans.

What I want to know: Will increased knowledge of what makes influenza strains more lethal get used more to reduce the spread of influenza than it will get used by crazies to make lethal strains? Initially I expect this knowledge to be more useful on the side of good. But in the longer run biotechnologies will make the creation of custom virus strains easy for amateurs.

Advances in microfluidics will enable the development of beneficial treatments including full body rejuvenation therapies. But as microfluidic chips become cheaper and the software for controlling these devices becomes more powerful and easier to use individuals in personal labs in their own bedrooms or cellars will be able to develop customized lethal pathogens.

Reasons for optimism? First off, most people do not want to die. The internet enables large numbers of people to contribute solutions to problem. If malicious biological script kiddies start tossing out killer pathogens into the world's population the number of people who will organize to develop defenses will far exceed the number generating killer pathogens. Also, those fighting for the defense will probably be much smarter than those who are malicious. I am expecting people who feel they have low status to tend toward malicious acts.

But will sheer numbers of smart brains be sufficient to defeat malicious makers of dangerous pathogens? Or will defense against designer pathogens run into difficult problems similar to the relative difficulties of stopping versus delivering nuclear bombs? My fear is that the defensive side will be the more difficult.

When it comes to natural pathogens I expect human brains controlling computer simulations and automated equipment to near totally defeat them. Biological evolution won't be able to keep up with computers and microfluidic devices. So we'll reach a point where most of the remaining big killer pathogens cease to rack up big death tolls..

By Randall Parker    2007 February 03 11:51 AM   Entry Permalink | Comments (1)
2006 November 18 Saturday
H5N1 Flu Strains Mutate For Easier Human Spread

Yoshiro Kawaoka and colleagues at University of Wisconsin in Madisonj have found that some strains of H5N1 bird influenza have mutations that increase their ability to bind to human cells.

Two mutations in the viral hemagglutinin surface protein independently enable H5N1 influenza A virus to bind to human receptors, researchers report in Nature this week.

That's not good news. Avian influenza is highly lethal for infected humans.

Two mutations found in human patients increase binding of the virus to human cells.

Whereas viruses from chickens and ducks could only recognize avian receptors, some viruses from human patients could recognize both human and avian cell receptors. "Once we identified the differences between the isolates, we narrowed down the specific changes that make avian H5N1 recognize the 2,6 receptors," Kawaoka explained. The changes were just two mutations, at positions 182 and 192 on the hemagglutinin sequence.

Half the 250 people known to have been infected by H5N1 have died. If the virus mutates into a form that is transmitted easily between humans while still retaining much of its current lethality you would be well advised to buy a lot of supplies and avoid contact with other humans for several months while a vaccine gets developed.

A highly lethal H5N1 would probably become less lethal with time since less sick people will get around more and spread the disease more widely. So you are also better off avoiding the disease in the early months in hopes that if eventually exposed you'll get a less lethal version.

It is also possible that antibodies taken from infected people who recover could be extracted and used as treatment for those who get it later. So, again, don't be the first one on your block to get a pandemic influenza virus.

In a few years the risk from H5N1 or any other influenza strain will go down due to development of faster means to scale up and produce vaccines. Also, better drugs will be found for suppressing the excess inflammation response by which more deadly influenza strains probably kill.

By Randall Parker    2006 November 18 01:05 PM   Entry Permalink | Comments (1)
2006 October 13 Friday
Bird Flu Vaccines Cross-Strain Benefit

Bottom line: If you got a vaccine shot from one strain of H5N1 bird flu and then later got a different vaccine shot for a different strain of H5N1 bird flu you'll get a stronger immune response from the second shot. That means if you got vaccine to an old H5N1 strain now and then an avian flu pandemic happened and you get a vaccine shot for the killer pandemic strain you'll get a strong immune reaction and better resistance because you had the earlier shot of a different strain. Vaccination by one strain of bird flu increases the immune response to a later strain of bird flu.

Officials were able to track down 37 people who agreed to take part. Each had received two shots as part of the vaccine study in 1998 against the form of the virus that had emerged in Hong Kong. Earlier this year each was again vaccinated with another shot targeting a different form of bird flu, the variant that swept through Vietnam in 2004 and 2005. Their immune response to the second shot was compared to the response in people who received shots for the first time in 2005. More than twice as many people who also received the shot in 1998 developed a protective antibody response against bird flu compared to people who had never been immunized against bird flu previously.

"We studied a relatively small group, so that certainly, this issue needs to be studied more thoroughly in a larger group of people," said John J. Treanor, M.D., professor of medicine and director of Rochester's Vaccine and Treatment Evaluation Unit. "If the findings hold up, then it might open up a number of options beneficial for planning. One might consider giving a priming shot to members of the community who would be a central part of the response if a pandemic were to occur, such as health care workers. You'd have people who were prepared as much as possible in advance."

The work is being presented at IDSA by research fellow Nega Ali Goji, M.D., who did the study with Treanor

The work addresses one of the features of bird flu that makes a potential pandemic so hard to fight: Like human flu viruses, bird flu mutates constantly, and by the time a vaccine has been produced to protect against one form of bird flu, it's very possible that another form, requiring a different vaccine, will have emerged that can move from person to person.

The results of the new study are similar to what doctors already know about giving "regular" flu shots. Every year millions of adults get an updated flu shot every year – one shot is enough, because their immune systems "remember" previous forms of the flu and help make the new shot each year effective. But small children who have never seen the flu before typically need two shots, a primer and a booster. The results from the new study indicate that, like small children who receive a regular flu shot, adults who have never encountered bird flu would benefit from a booster shot.

The two vaccines used in the study target viruses belonging to different "clades" or viral families. Both are H5N1 bird flu viruses, but the Hong Kong strain from 1997 belongs to clade 3, while the Vietnam strain from 2004 belongs to clade 1. Goji and Treanor found that the shot targeting clade 3 helps the body maximize the immunization against a virus in a different clade, clade 1. In other words, using the vaccines that are available now might help improve the response to the vaccines developed for a future strain of bird flu.

Very likely vaccination against some existing strain of H5N1 avian flu would also increase immune response to an infection by a future pandemic strain of avian flu. This means your odds of survival from a pandemic infection would be increased if you could only get yourself vaccinated against an existing known strain of bird flu.

These results argue for mass producing a bird flu vaccine using known strains. If such a vaccine was available I'd go get a shot. Partial immunity would be much better than boxes of N95 face masks.

By Randall Parker    2006 October 13 09:35 PM   Entry Permalink | Comments (1)
2006 October 02 Monday
1918 Influenza Death Toll From Excessive Immune Response

H5N1 avian flu might have the potential to mutate into a killer epidemic. So an understanding of how the most lethal modern flu epidemic killed its victims may yield information that'll help protect us. Reconstructed 1918 Influenza viruses delivered into lab mice in biosafety level 3-enhanced laboratory at the CDC in Atlanta caused run-away inflammation that explains the lung damage seen in 1918 flu victims.

Unlike typical seasonal flu, which strikes hardest at the very young, the elderly and those with compromised immune function, the 1918 flu disproportionately killed young people in the prime of life. Modern analyses of 1918 flu victim autopsy samples show extreme and extensive damage to lung tissues. This observation gave rise to the hypothesis that the 1918 flu virus infection provoked an uncontrolled inflammatory response leading to rapid lung failure and death.

To test this idea, Dr. Tumpey infected mice intranasally with one of four types of flu virus: human seasonal flu virus from a strain that circulated in Texas in 1991; lab-made viruses containing either two or five of eight viral genes from the 1918 virus; or a reconstructed virus containing all eight 1918 flu virus genes. Lung tissue from three infected mice in each group was removed on days 1, 3 and 5 post-infection and processed to destroy any virus. The mouse genetic material (RNA) was then extracted from these lung samples and sent to the University of Washington team for analysis.

Drs. Katze and Kash and colleagues examined the mouse RNA using microarrays to determine which genes were activated when exposed to each of the four viruses. This analysis showed that the immune response to the reconstructed 1918 virus containing all eight flu genes was much greater than to any of the other viruses with all eight genes, says Dr. Katze. In particular, genes involved in promoting inflammation were strongly and immediately activated following infection by the reconstructed 1918 virus. "We clearly see a dramatic and uncontrolled immune response in the mouse lungs as early as one day following infection with the reconstructed 1918 virus," he says. A complete understanding of the host's response to the 1918 flu virus, adds Dr. Katze, requires use of a fully reconstructed virus.

If the H5N1 bird flu virus mutates into a form easily transmissible between humans it might cause death by the same general mechanism. If that turns out to be the case then many of those who get infected and manage to recover are probably going to live with some permanent damage to their bodies. Severe inflammation is going to leave behind damaged and scarred tissue.

If a highly lethal flu pandemic breaks out your best bet is to isolate yourself for months while vaccine production gets ramped up. Whether you go into solitary isolation or as part of a family, group of friends, or small job work team, cut yourself off from the chains of transmission of the virus. If you need to go to stores or meetings use N95, N100, or P100 face masks. Avoid touching surfaces. Try to avoid going in-doors with people who are not in your personal isolation group.

If you want to prepare for a pandemic here are my top suggestions:

  • Have at least 3 months of food and of anything else you would use over a period of a few months.
  • Stockpile some N95 and N100 face masks.
  • Build up your savings. Be able to pay the rent or mortgage and other bills for months without going to work.
  • If you have a lot of money get a self-contained place you can retreat to that is in a rural area.

If you can isolate yourself you won't get infected. It is as simple as that.

The longer we go without a flu pandemic the less the risk of an eventual pandemic killing any of us. Drugs that prevent extreme inflammation response will be found. Methods to scale up vaccine production more rapidly are on the way too. In 10 years I do not expect pandemic flu strains to pose a major threat to industrialized countries. We'll have the biotechnologies needed to protect ourselves pretty rapidly from deadly strains of influenza.

By Randall Parker    2006 October 02 04:54 PM   Entry Permalink | Comments (3)
2006 July 26 Wednesday
Potent H5N1 Avian Influenza Vaccine Developed

GlaxoSmithKline (GSK) has developed a vaccine for H5N1 flu that is potent in much lower doses than previously tested H5N1 vaccines.

In a clinical trial, 80% of volunteers who received two vaccine doses containing 3.8 mcg of antigen with an adjuvant (a chemical that stimulates the immune system) had a strong immune response, the British-based company said in a news release. A typical dose of seasonal flu vaccine is 15 mcg.

"This is the first time such a low dose of H5N1 vaccine has been able to stimulate this level of strong immune response," GSK Chief Executive Officer J.P. Garnier said in the news release.

By comparison, an H5N1 vaccine developed by Sanofi Pasteur induced a good immune response in 67% of volunteers who received two 30-mcg doses with an adjuvant, according to findings reported in May. The US government is stockpiling the Sanofi vaccine.

Garnier called the GSK vaccine a breakthrough because, with the effectiveness of the low dose, a given amount of antigen will go much further than it would otherwise.

"The meaning of this is that we are going to be in a position, starting later this year, to produce hundreds of millions of doses of an effective pandemic vaccine, so this is a big breakthrough," Garnier said on BBC Radio, as reported today by Agence France-Presse (AFP).

World influenza vaccine production capacity is too low in event of a deadly pandemic flu outbreak. A vaccine that is potent in such a small dose greatly expands the number of doses of vaccine that could be made in a year in response to a deadly pandemic.

Other vaccines against H5N1 are much less potent.

Previous attempts to produce a low dose vaccine had been unsuccessful, with required doses as high as 180 micrograms. Companies then tried adding an adjuvant – a chemical which stimulates the immune system and increases the potency of a vaccine. But, again, results were disappointing.

We need newer and far more easily scaled vaccine production technologies. The lead time for vaccine production is several months. The production capacity is low because only a small fraction of the world's population gets vaccinated for the flu in typical years. A better vaccine production method would be faster and scale up rapidly with easily produceable capital equipment.

By Randall Parker    2006 July 26 10:55 PM   Entry Permalink | Comments (0)
2005 September 27 Tuesday
Dogs Face Deadly H3N8 Influenza From Horses

As humans face the growing possibility of a deadly flu pandemic our four legged friends demonstrate just how much they have in common with us. A deadly influenza strain that has jumped from horses to dogs is producing headlines similar to what we can expect to see when the next human influenza pandemic hits. The horse influenza H3N8 has mutated and jumped to dogs and killed greyhounds in 7 states.

The virus, which scientists say mutated from an influenza strain that affects horses, has killed racing greyhounds in seven states and has been found in shelters and pet shops in many places, including the New York suburbs, though the extent of its spread is unknown.

...

The virus is an H3N8 flu closely related to an equine flu strain. It is not related to typical human flus or to the H5N1 avian flu that has killed about 100 people in Asia.

Fido, Spot, and Rover are in danger. But humans can control the spread of a canine influenza outbreak a lot more easily than they can control a human outbreak. Humans travel greater distances and congregate together a lot more. While Rover is at home in the backyard waiting for people to come home and barking plaintively through the fence at dogs getting walked Johnnie is at grade school fighting with Billy, Bobby, Biff, and Brett on the playground and passing pathogens around in the process. His sister Jill is playing pattie cakes with Suzie and Taylor and passing along germs too. Johnnie's Dad is flying back from a business meeting in Singapore with regional manangers from Thailand, Canton, and Indonesia. Mom is at Pilates with a bunch of other women all touching the same floors, door knobs, and railings with their sweaty skin. Or maybe Mom is carrying on an affair with another law firm partner. Oh, and Mom's sister is waitressing at a busy packed restaurant to work through law school.

Humans have been exposed to this virus from horses for a long time with no reports of cross-overs into humans.

There is no evidence that it has spread to humans, or that it ever will. But at a Monday press conference, federal officials said they are monitoring the health of exposed dog owners -- because a virus that jumps species once could do it again.

...

"We have never been able to document a single case of human infection with this virus,'' said Ruben Donis, a researcher with the federal Centers for Disease Control and Prevention and principal author of the study.

But a virus that has managed to hop into dogs might now be closer to human compatibility. Anyone have scientific reasons to think this might be the case?

The CDC says don't panic even though it appears to kill 5% to 8% of dogs..

"We are going to monitor all cases of human exposure, but at this point there is no reason to panic," said Ruben Donis of the federal Centers for Disease Control and Prevention in Atlanta. Donis noted that it has been known for about 40 years that the virus causes the flu in horses, with no reports of its infecting humans. Tests also indicate it is sensitive to antiviral drugs.

...

Although the mortality rate from the new flu virus remains unclear, so far it appears to kill 5 to 8 percent of infected dogs.

Well, what a human-centric attitude. Don't panic? Imagine a pandemic flu virus that killed 8% of humans was in the lose. Oh wait, the CDC would still say there is no reason to panic. But that only makes sense. There's never any reason to panic. Panic is a maladaptive response. But sometimes desperate measures are called for. Just stay level headed.

Since the dog flu is responsive to Tamiflu and amantadine I see this as yet another reason to stockpile Tamiflu. Fido's life might depend on it. What if a human pandemic breaks out, you stay totally healthy, but Fido comes down with a bad case of the flu? I can tell you right now that those human-centric public health authorities aren't going to let you get any Tamiflu for Spot or Scooby Do. No way. You have to stock up ahead of time if you want to protect your dog during a human flu pandemic.

Continue to walk your dog and let neighborhood packs congregate.

The C.D.C., which is tracking the disease, issued no official recommendations. But Dr. Crawford urged pet owners to continue to walk healthy dogs, visit dog runs, use boarding kennels and otherwise let animals congregate.

But, Dr. Crawford added, owners should "use common sense," including isolating dogs with any symptoms of respiratory disease for up to two weeks and alerting a veterinarian's office before taking in a sick dog for treatment.

But we need continued press coverage of this problem. Dog owners need to know when H3N8 comes to their neighborhoods.

Update: Dr. Brad Fenwick thinks the mortality rate is lower than Crawford's estimate.

Dr. Brad Fenwick, vice president for research at the College of Veterinary Medicine at Virginia Polytechnic Institute, said he thinks mortality from this flu is even less than estimated by Crawford. If infected dogs are treated, mortality can be much lower, Fenwick said in a telephone interview.

From the CDC press conference: Dr. Ruben Donis:

So what about the implications for public health? We must keep in mind that this H3N8 equine influenza virus has been in horses for over 40 years. In all these years, we have never been able to document and single case of human infection with this virus. So that is something that I want everybody to take note of so to dispel, you know, major panic. That's not to say that there isn't any risk. We are going to monitor all cases of possible human exposure, but, this point, there is no reason to panic.

Dr. Cynda Crawford:

Only a minority of dogs, a small number of dogs, experience complications such as pneumonia, just like the humans infected with influenza, certain populations of humans are more prone to development of pneumonia. And it's a small number of humans compared to everyone else.

So that is the same with canine influenza virus. It's a small population of dogs that will develop complications, most likely bacterial complications and these dogs do need to be--have their treatment supervised by a veterinarian.

In addition, since not all dogs will show a clinical syndrome, showing that they have a respiratory infection, there is a minority that are infected with the virus, but will not show clinical signs to announce to everybody that “I am sick.” And it is very difficult to find these dogs in the dog population. And we're working on a more rapid means of identification.

If bacterial infection sets in as a complication that obviously can get treated by antibiotics. Also, Tamiflu and amantadine can slow the virus itself.

By Randall Parker    2005 September 27 02:05 PM   Entry Permalink | Comments (12)
2005 September 19 Monday
United States Orders French Bird Flu Vaccine While Indonesian Cases Suspected

George W. Bush has decided to order an experimental French avian flu vaccine.

At the United Nations on Wednesday, President Bush proposed an "international partnership" to combat the disease, and the United States announced last week that it had placed orders for $100 million worth of a promising but technically unlicensed vaccine that is under development by the French drug maker Sanofi-Aventis.

If it was up to me I'd take money away from Bush's massive Gulf Coast mini-Great Society boondoggle (why subsidize rebuilding in a flood plain where hurricanes will hit again and again?) and use it instead to develop better influenza vaccine production technologies and other measures to protect against the inevitable next influenza pandemic. Why subsidize the movement of people back into harm's way when we could instead fund research that would remove people from harm's way? But my knee jerk use of rational analysis keeps placing me outside of the emotional mainstream.

We are overdue for the next big influenza pandemic and it is just a matter of time till the pandemic happens.

"We know we're overdue for an influenza pandemic strain, and we know it will occur, but we don't know when or even exactly what virus will cause it," said Dick Thompson, a WHO spokesman. "It is possible that the virus won't be H5N1 at all or that this virus will change in a way so that the vaccine under development doesn't work against it."

Thompson added that government orders for unproven vaccines still are worthwhile because they provide incentives for companies to do vaccine development work against H5N1. That makes sense. The companies will be further up the learning curve on H5N1 and will also have more vaccine production facilities in place available to switch over to a different vaccine variant once the exact pandemic strain emerges.

The backdrop to these statements is the avian flu news from Indonesia. Indonesia has 4 dead from the H5N1 avian flu strain and birds all over the Indonesian islands have the flu.

The developments highlighted Indonesia's continuing struggle against bird flu, which is endemic in chicken flocks across the sprawling island nation and has killed four humans since July, the most recent being a 37-year-old woman who died nine days ago.

3 Indonesian children have suspected cases of H5N1 avian influenza.

Three Indonesian children are suspected of having been infected with bird flu, a health official said, while the Jakarta zoo remains closed over an outbreak of the disease.

'There are now three suspected cases of bird flu infection, all children,' said Sumardi, the health ministry's acting spokesman.

Unlike other (and rather poor) countries in the region Indonesia says it doesn't have the money to do massive culls of commercial poultry populations which have bird flu.

Apriyantono later told reporters his ministry had requested more funds to handle the outbreak, but said the government had little money to conduct a mass slaughter of poultry or birds.

"Depopulation will need a huge amount of funds. This year, we need more funds for avian influenza to do research, surveillance and selective depopulation."

The WHO would support recommendations by the World Organisation for Animal Health and by the U.N. Food and Agriculture Organisation (FAO) for a mass cull in Indonesia, Petersen said.

I'd love to know what the cost of a huge domestic bird depopulation would cost in Indonesia. Suppose the US withdrew from Iraq and used some of the money against domestic avian flu in poor countries. How many weeks of fighting in Iraq would yield enough money to pay for a cull of infected birds in Indonesia, Cambodia, and Laos?

WHO regional director Shigeru Omi says poor Asian farmers are a weak link for stopping an avian flu pandemic.

The WHO regional director for Western Pacific, Shigeru Omni, said at the opening of a WHO conference in New Caledonia that poor Asian farmers are a weak link in the fight to contain the disease. He said these farmers are reluctant to report bird flu outbreaks because of a lack of financial incentives to do so.

WHO says countries should hold a mass culling when an outbreak occurs, but some nations refuse. Indonesia has launched a vaccination drive for poultry, but has carried out only limited culling because it lacks the money to compensate farmers.

When the pandemic comes it will cost industrialized countries trillions of dollars. Why not spend a small fraction of that up front to reduce the odds of the pandemic in the first place? As one of the B-52s women singers once sang "I'm just asking!".

World Health Organization (WHO) Indonesia country representative Georg Petersen says that farmers living in close proximity to their chickens makes the spread of avian flu to humans hard to control. At the same time an Indonesian government official says Indonesians should just accustom themselves to getting sick from H5N1 avian influenza.

``The problem with this country, as in many Asian countries is that a large portion of the chickens are raised by farmers in their backyard and even within the cities, people are raising chickens and this is very difficult to control,'' Petersen said.

Indonesians ``will have to be prepared to live together with bird flu, as it has with dengue,'' agriculture minister Anton Apriantono told reporters while visiting Pasar Cempaka Putih, a traditional market that sells live poultry in central Jakarta today. Dengue, which causes, fevers, rashes, headaches, muscle pain and sometimes death, is an annual occurrence in Indonesia.

Bottom line? Your own considerable future risk of getting killed by an H5N1 avian influenza pandemic comes from an attitude prevalent in Third World countries that lots of disease sicken and kill people so why get worked up about just one more infectious disease?

By Randall Parker    2005 September 19 02:06 PM   Entry Permalink | Comments (10)
2005 September 02 Friday
France Prepares For Avian Flu Pandemic

France is taking bigger steps than most Western countries to prepare for a potential avian flu pandemic.

French newspaper Liberation said the government had already acquired 5 million doses of the antiviral drug Tamiflu, produced by Swiss pharmaceutical giant Roche, and was planning to raise the level to 14 million by the year end.

France has a population of over 60 million people. Not all the population would get sick. 14 million Tamiflu doses might be enough if many steps were taken to reduce the rate of transmission of the flu virus.

The French government is also negotiating contracts to produce large stocks of flu vaccines. But pre-stocking flu vaccines might not work since the avian H5N1 viruses in birds are still mutating. If a viable strain emerges in humans it might look antigenically very different than any strain used now to base a vaccine on.

The French government is also purchasing a couple hundred million face masks.

The number of protective face masks in stock would be increased to 200 million by the start of next year from 50 million.

One wonders how long these masks would last. The 3M N100 and P100 masks last for 150 hours. However, most masks last for about an order of magnitude less time. Therefore individuals out in public all day would need many masks to get through the length of time of a pandemic.

By Randall Parker    2005 September 02 01:44 PM   Entry Permalink | Comments (34)
2005 August 05 Friday
Acambis Attempts Universal Flu Vaccine

Acambis thinks they might have a way to build a universal vaccine against the new flu strains that pop up each year.

Cambridge, UK and Cambridge, Massachusetts – 4 August 2005 – Acambis plc (“Acambis") (LSE: ACM, NASDAQ: ACAM) has commenced development of a potentially breakthrough new influenza vaccine that could offer permanent protection against influenza and may also offer protection against influenza pandemics. Influenza vaccines are currently administered annually.

Acambis has entered into a research collaboration and licensing agreement with the Flanders Interuniversity Institute for Biotechnology (“VIB"), a Belgian research institute.

Acambis and VIB will work together to develop a vaccine against both A and B strains of influenza, using Acambis' influenza A vaccine candidate that it acquired from Apovia earlier in the year and additional technology licensed from VIB. Apovia is a US biotechnology company and started development of the influenza A vaccine candidate in 2000, having originally licensed the technology from VIB. Walter Fiers, emeritus professor of Molecular Biology at the University of Ghent, is an inventor of the patent rights licensed from VIB.

The aim of the research collaboration would be to generate a ‘universal' vaccine candidate that would protect against both A and B strains of influenza and, more importantly, would not require annual changes to the formulation. This contrasts with current influenza vaccines that need to be changed, generally each year, to cope with genetic drift, mutations that occur in influenza strains circulating in nature, as well as major genetic shifts that can result in influenza pandemics. The need to change vaccine formulations each year results in delays in initiating vaccine coverage.

Unforunately it sounds like they are not far enough along to offer anything against the H5N1 avian flu strains should avian flu manage to mutate into a form that spreads easily between humans in the next few years.

The appeal here is not just the universality of the vaccine. Their use of baterial fermentation technology addresses the big problem of slow production and poor scaling of today's chicken egg-based influenza vaccine production technology.

The initial vaccine candidate against influenza A is currently in pre-clinical development. It is manufactured using recombinant bacterial fermentation technology, which aims to provide time and cost efficiencies compared with traditional egg-based production methods.

They haven't yet proven their vaccine will be universal but they are hopeful.

Walter Fiers, Professor emeritus, University of Ghent and VIB, said:

“The research and pre-clinical development carried out so far supports the promising potential of a universal, M2e-based influenza vaccine. In view of the conservation of the M2e structure, vaccination against all human influenza virus strains may become possible, even before new epidemics or pandemics have started to spread. Moreover, the vaccine is a recombinant protein with a defined chemical structure which can be rigorously characterised and produced on a large scale. We are pleased to collaborate with Acambis in the further development of this promising vaccine."

Could this vaccine save us from avian flu? If avian flu breaks out into a pandemic could this approach be scaled up rapidly without clinical trials? Even if the vaccine would be risky in an emergency where the alternative is a decent chance of dying from a killer flu a rapid deployment of this vaccine might be worth the risk.

By Randall Parker    2005 August 05 10:05 AM   Entry Permalink | Comments (4)
2005 August 04 Thursday
Prompt Response Might Stop Avian Flu Pandemic

We have some bad news and we have some possibly good news.

If Asian bird flu mutates into a form that spreads easily between humans, an outbreak of just 40 infected people would be enough to cause a global pandemic. And within a year half of the world’s population would be infected with a mortality rate of 50%, according to two studies released on Wednesday.

And yet, the models show, if targeted action is taken within a critical three-week window, an outbreak could be limited to fewer than 100 individuals within two months.

This result comes out in a pair of papers published in Nature and Science by teams of British and American researchers.

Neil Ferguson, a professor at the Imperial College in London and lead author of the Nature paper says that if the pandemic happens half the world's population could be infected within a year.

Prof Ferguson said if nothing was done, half the world could be infected within a year. But a stockpile of Tamiflu, along with a policy of closing schools and workplaces, could have more than a 90 per cent chance of stopping a pandemic virus.

Bummer dudes. If I survive I'll probably have a much smaller readership. Could all my readers please plan in advance and buy provisions to allow themselves to flee to isolated cabins for a year? I don't have a big marketing budget to attract new readers. So you guys and gals have got to be careful and stay alive. Oh, and stop smoking, get more exercise, eat better food, lose weight, and don't drink and drive.

During the pandemic using cellular broadband on broadcast towers you'd still be able to read me from your mountain cabins while I hole up in a cabin of my own. Note to self: Buy a cabin with a water well and a bunch of solar panels and batteries and in sight of a cellular internet modem tower. Stock it with lots of pop corn, Total cereal, and other vital necessities.

The American team also found that early intervention with antivirals and quarantines has the potential to stop a pandemic.

Another team from Emory University in Atlanta, the US, led by Dr Ira Longini, simulated an outbreak in a population of 500,000 in rural Thailand, where people mixed in a variety of settings, including households, schools, workplaces and a hospital.

Provided targeted use of antiviral drugs was adopted within 21 days it would be possible to contain an outbreak, they found, as long as each infected person was not likely to infect more than an average of 1.6 people.

If it was more infective than this, household quarantines would also be necessary, they said.

But among the many reasons such a strategy might fail is the possibility that the outbreak strain could develop esistance to the anti-viral drug Tamiflu (chemical name oseltamivir).

Another problem is that the earliest victims must be identified promptly.

Professor Ferguson then considered what would happen if Tamiflu were given rapidly to everybody within a 5km (3.1m) or 10km radius of an infected person, and measures were taken to reduce contact by closing schools and workplaces.

These approaches will contain an outbreak, but only if Tamiflu is given swiftly, preferably within 48 hours of a case being diagnosed. Prevention must begin before more than 30 to 40 people are infected, and 90 per cent must take the drugs they are given.

Well, imagine that the early victims are in Laos or Cambodia or Burma (all quite plausible) and since large areas of those places are pretty primitive what if nobody of importance notices for weeks? Also, to enforce household quarantines and other measures one needs a fully functional government with plenty of public health workers. Well, in some parts of the world government is dysfunction or effectively non-existent.

Even with prompt response we'd still have to get lucky.

"If we end up with a pandemic like [previous catastrophic pandemics], we'll have a lot of people dead," said study team member Elizabeth Halloran, professor of biostatistics at Emory University in Atlanta, Georgia.

Halloran added that the simulations show that it should be possible to contain an outbreak at its source. But the results are unpredictable. "We have shown in these simulations that—even given the same [hypothetical] situation—sometimes when we intervene it's successful and sometimes it's not," Halloran added.

Bottom line: Do not count on this approach working even if the political will and resources are available to execute the containment strategy.

The experts are aware that success of a prompt containment strategy depends on many "ifs".

"The models show that if you combine well-directed, targeted treatment with some social interventions like closing schools, ideally together with some vaccination, it's conceivable you'd be able to stop the epidemic," said Anthony S. Fauci, chief of infectious diseases at the National Institutes of Health, which funded much of the work through its National Institute of General Medical Sciences.

But the odds of success are tempered by many "ifs," Fauci and others warned.

Here's one problem with this strategy: A reluctance to commit resources. They assume a few million doses of Tamiflu available and some panel or person authorized to employ it. Well, as it stands now the WHO is reluctant to raise the warning level for a pandemic because raising the level causes stuff like the use of Tamiflu stocks. They know if they use it prematurely they will basically shoot their guns but without ammo to reload. So there is going to be a bias against committing resources until absolutely certain. Well, how to determine that a strain that has pandemic capability has finally emerged and how to do that very quickly?

Suppose that the WHO and national governments got together 10 million or 20 million Tamiflu doses. Then public health officials could afford to commit resources against each potential outbreak before being absolutely sure. Would this work? Maybe. But then again, maybe widespread use of Tamiflu would help select for Tamiflu-resistant strains.

But there's another problem: The H5N1 strains that are popping around in animal populations could mutate into a human pandemic capable form more than once. We might need to stop it 2, 3, 4, or 5 times. Are we going to get that lucky? Heck if I know. But I'm not optimistic.

I think governments and public health officials ought to consider the rapid development and widescale delivery of vaccines to populations in Southeast Asia right now. Even if the vacines would be only partially effective against some future avian flu strain the ability to slow the spread of a new strain using partial immunity might give the containment strategy a much better chance of working.

My joking aside, this is serious business. Lots of us could die. We ought to be doing orders of magnitude more to avoid getting killed by an avian flu pandemic. Think about it. Complain to your elected representatives. Buy the sorts of supplies you'd need to survive a major societal disruption.

Update: Even a slowing of the pandemic would provide more time for vaccine development and production.

"Our findings indicate that we have reason to be somewhat hopeful. If -- or, more likely, when -- an outbreak occurs in humans, there is a chance of containing it and preventing a pandemic. However, it will require a serious effort, with major planning and coordination, and there is no guarantee of success," said coauthor Elizabeth Halloran of Emory University.

"Early intervention could at least slow the pandemic, helping to reduce morbidity until a well-matched vaccine could be produced," she said.

The danger of avian flu is that the virus could develop into a new strain that could be transmitted among humans. The virus might mutate, or it might jump over to a human already infected with the flu and then mix, or "reassort," with the human flu virus. Because humans would have little or no immune protection against this strain, it could potentially cause a massive pandemic.

"There were three influenza pandemics in the 20th century alone. The threat of another pandemic, related to avian influenza, is real and very serious. Fortunately, as the new study shows, for the first time in human history, we have a chance of stopping the spread of a new influenza strain at the source through good surveillance and aggressive use of public health measures," said Katrina Kelner, Deputy Editor, Life Sciences, at Science.

The effectiveness of containment depends on quick decisions to do targeted antiviral drug use, a fairly low multiplier for how many others each infected person passes the virus on to, a high level of use of antiviral drugs, and effective quarantine measures.

They found that targeted use of antiviral drugs could be effective for containment as long as the intervention occurred within 21 days and the virus' reproductive number (which represents the average number of people within a population someone with the disease is able to infect) had a relatively moderate value of roughly 1.6.

A process of administering antiviral drugs to the people in the same mixing groups as the infected person, called TAP for "targeted antiviral prophylaxis," could contain the outbreak as long as it reached 80 percent of the people targeted. A related strategy, GTAP, for "geographically targeted antiviral prophylaxis," which targets people within a certain geographic range of the initial case, produced similar results as long as it achieved coverage of 90 percent.

Vaccination before the outbreak, even with a vaccine that is poorly matched to the actual virus strain, increased the effectiveness of TAP and GTAP.

For even higher viral reproductive numbers, household quarantines would also be necessary to contain the virus. A combination of TAP, prevaccination and quarantine could contain strains with a reproductive number around 2.4. A value of 2.4 is relatively contagious, though some other viruses such as measles are substantially higher. In all cases, early intervention would be essential.

We can't have a wonderful long future if we die first. Future rejuvenation therapies are useless to anyone who dies from bird flu next year.

Update: Do not expect Western governments to allocate sufficient vaccines and drugs to implement the early preemption strategy to stop an outbreak.

Would the United States, Europe and Japan be willing to donate their precious vaccine supply to mount this long-shot defense? This is perhaps the biggest unanswered question in pandemic flu planning -- and one likely to be answered only at the moment of truth.

Officially, it is a possibility.

"If it was done in consultation with the WHO [World Health Organization] -- and with other governments that would make contributions, as well -- we would be more likely to consider it," said Gellin at HHS. But observers both in and out of the government said, not for quotation, that they doubt the U.S. government would ever send a significant amount of its vaccine stockpile overseas.

Production of a sufficient supply of vaccine could take years. The economic disruption of a pandemic will be enormous. I am expecting an economic depression. The threat of terrorism will seem tiny by comparison.

Also see my previous posts "Yet Another Avian Flu Preparedness Warning Report" and "More Warnings On Avian Flu Danger To Humanity".

By Randall Parker    2005 August 04 05:32 PM   Entry Permalink | Comments (13)
2005 June 27 Monday
Yet Another Avian Flu Preparedness Warning Report

Trust for America’s Health joins the list of organizatons warning about the potential danger of an avian flu pandemic in humans. PDF format)

WASHINGTON, June 24, 2005 – Trust for America’s Health (TFAH) today released state-by-state projections that found over half a million Americans could die and over 2.3 million could be hospitalized if a moderately severe strain of a pandemic flu virus hits the U.S. Additionally, based on the model estimates, 66.9 million Americans are at risk of contracting the disease. The study also found that the U.S. currently only has stockpiled 2.3 million courses and has placed orders for an additional three million courses of antiviral pharmaceuticals (produced as Tamiflu by Roche Pharmaceuticals), which would likely be available in 2006. This would be enough to cover 5.3 million Americans, leaving over 60 million who could be infected and would not be able to receive medication before an effective vaccine to combat the flu strain is identified and produced.

TFAH’s numerical projections are included in a new report, “A Killer Flu? ‘Inevitable’ Epidemic Could Kill Millions.”

“This is not a drill. This is not a planning exercise. This is for real,” said Shelley A. Hearne, DrPH, Executive Director of TFAH. “Americans are being placed needlessly at risk. The U.S. must take fast and furious action to prepare for a possible pandemic outbreak here at home.”

“The Government Reform Committee has held several hearings over the last few years to let people know that the flu is not something to take lightly,” said U.S. Congressman Tom Davis (R-VA), Chairman of the House Government Reform Committee. “TFAH's report clearly demonstrates that the emergence of a pandemic flu could exact a tremendous toll on U.S. health and economic stability. In order to identify problem areas and prioritize planning and response efforts, the Committee will hold a hearing next week on the threats posed by a potential flu pandemic.”

Dr. Hearne will be testifying Thursday, June 30th, before the House Government Reform Committee on U.S. preparedness for pandemic and annual flu. Some of the TFAH report’s other findings include:

  • While estimates find that over two million Americans may need to be hospitalized during a pandemic outbreak, the U.S. currently only has approximately 965,256 staffed hospital beds.
  • The U.S. has not adequately planned for the disruption a flu pandemic could cause to the economy, daily life, food and supply distributions, or homeland security.
  • The U.S. lags in pandemic preparations compared to Great Britain and Canada based on an examination of leadership, vaccine development, vaccine and antiviral planning, health care system surge capacity planning, coordination between public and private sectors, and emergency communications planning.

TFAH provides a series of detailed recommendations to help ensure the U.S. is better prepared regardless of whether a pandemic occurs as soon as this year or in several years. With a crisis looming, the U.S. plan for the pandemic should be finalized and the President should designate an official with authority to coordinate the U.S. response across federal agencies. Other top level recommendations include taking:

  • Immediate steps of outbreak tracking, stockpiling medical supplies, and developing emergency communications plans;
  • Intermediate steps of stockpiling additional antivirals and developing surge capacity plans for hospitals and health care providers; and
  • Longer range steps to increase vaccine production and the development of new technologies for vaccines.

I figure, humans being humans, we'll have a big pandemic and millions will die and only afterwards all the recommendations about building more rapid vaccine production technologies, stockpiling of medical supplies, and better methods of reducing human-to-human transmission will be implemented. The warnings coming from infectious disease experts and others are being discounted as the standard exaggerated doom and gloom fare of coming disasters.

The full report projects a high economic cost from a pandemic. (PDF format)

The estimated economic impact of a pandemic flu outbreak in the U.S. today, based on projections from the relatively mild 1968 flu epidemic, would be $71.3 to $166.5 billion due to death and lost productivity, excluding other “disruptions to commerce and society.”6

Note the real possibility that the avian flu could have a higher lethality rate than the 1918 flu. So the economic costs, number of hospitalizations, and total deaths could be much greater than the estimates provided above.

Some countries could be politically destabilized by the effects of a flu pandemic. Though I'm going to go out on a limb here and guess that in Africa with so much disease already a flu pandemic might seem like nothing out of the ordinary.

The U.S. would be impacted by the global implications as soon as a pandemic outbreak occurred in any part of the world due to the interdependence of economies. Sectors, such as hospitals and the health care system, which rely on supplies manufactured in other parts of the world, including Asia, would feel immediate repercussions and supply shortages. Travel restrictions, possible limitations on public gatherings and events, and other measures taken to limit the spread of disease would also have rapid and far reaching repercussions. Since a pandemic could likely result in political and economic destabilization, particularly in developing countries, it poses serious national security concerns for the U.S.

Those who think the threat of the avian flu is overblown need to learn about the larger historical context: Influenza pandemics have occurred regularly in human history and statistically speaking we are overdue for the next one.

Based on historical trends and projections, virologists and epidemiologists predict a new flu pandemic will emerge three to four times each century.8 Health officials around the world are troubled by the severity of the “avian flu” circulating in Asia, which scientists refer to as the H5N1 flu strain. They fear this avian flu could become the next pandemic for humans. The regional director of the WHO for the Western Pacific region stated in February 2005 that the “world is now in the gravest possible danger of a pandemic.”9

We currently run the risk that the avian flu will not only be the next pandemic but that it will be much more lethal than the average pandemic.

The economic disruptions of a pandemic would reach the United States rapidly due to the interdependent nature of economies.

The U.S. has not assessed or planned for the disruption a flu pandemic could cause both to the economy and society as a whole. This includes daily life considerations, such as potential school and workplace closures, potential travel and mass transit restrictions, and the potential need to close stores resulting in complications in the delivery of food and basic supplies to people. Daily life and economic problems would likely emerge in the U.S. even before the pandemic flu hit the country due to the global interdependence of the world economy.

Put aside for the moment the medical issues (e.g. virus manufacture, acute patient care, drug production, medical supplies shortages, and so on). Think about the problem at the level of human organization to reduce pathogen transmission in ways that minimize economic disruption. We have the potential to develop and find ways to carry out economic functions with less human-to-human exposure. The development of procedures and products, the training of work forces, and the purchase of key pieces of capital equipment could reduce the amount of human contact involved in most types of economic activity. This would simultaneously reduce the rate and extent of spread of the pandemic virus and reduce the size of the economic disruption caused by the virus.

The rate of infection of the population might be between 25% and 50%. But with better economic organization and practices human-to-human contacts and transmission could be greatly decreased.

  1. The WHO has estimated that there would be a “contraction” rate of 25 percent for this flu strain. This means they warn that countries should be prepared for approximately 25 percent of their populations to get sick from the pandemic virus. Other scientists have estimated that up to 50 percent of countries’ populations could become infected.
  2. The current strain of the avian flu is viewed as significantly more lethal than the 1968 pandemic flu strain. A high-level pandemic, such as the 1918 pandemic, is considered to be six times more lethal than the 1968 flu.19 The projections below reflect a mid-level estimate of a three times higher rate. These numbers are reflected in the “Projected Dead” column in the table below. The range of estimates, from low level to high level severity death rates, can be found in Appendix A.
  3. Due to the severity of the avian flu strain, experts also believe that it would result in a much higher hospitalization rate than estimates using the 1968 strain. The estimates below, in the “Projected Hospitalizations” column, reflect a mid-level estimate of a three times higher rate. A more virulent strain of flu, changes in medical care and treatment procedures, and an aged population are all factors behind this projection. The range of estimates, from low level to high level severity hospitalization rates, can be found in Appendix A.

For Americans who become infected their odds of getting anti-viral medication will be less than 1 in 12. For people on most other countries their odds will be much lower. For anyone who has stockpiled your own personal Tamiflu supply your odds of getting anti-viral treatment are excellent - unless you tell too many people about your stockpile and someone steals it.

As of May 2005, the U.S. has stockpiled 2.3 million courses of the antiviral medication Tamiflu, which could be used as a treatment in the event of an outbreak, and intends to order approximately three million more with funds recently appropriated by Congress to total 5.3 million. The WHO is currently estimating that an avian flu epidemic could impact 25 percent of countries’ populations.

In the U.S., this means it could affect nearly 67 million individuals, based on FluAid projections and population numbers. With the current level of the U.S. Tamiflu order, over 61.5 million Americans who could be infected would not receive antiviral medication. If the U.S. orders additional courses of Tamiflu, they would not be available until 2007, unless production capacity significantly changes.

The Brits have ordered enough Tamiflu anti-viral drug to cover a quarter of their population. If the US government decided to do so it would have to wait till 2007 to have the needed number of doses.

Several other countries have already ordered enough Tamiflu to protect between 20-25 percent of their populations in case of an outbreak. The U.S. is already behind in the queue to place an order for the medication, for which there is a single manufacturer worldwide -- Roche Pharmaceutical, which is located in Switzerland. In testimony before the U.S. House of Representatives Health Subcommittee of the Energy and Commerce Committee, the medical director for Tamiflu of the Roche company explained that historically they have not produced the levels of Tamiflu required for global stockpiling. To help accommodate the growing concerns and orders, they have increased production of the antiviral nearly eight-fold since 2003.42

On March 1, 2005, the British government announced that it was taking steps to procure 14.6 million courses of Tamiflu.43 This procurement would cover 25 percent of the British population, the rate WHO has recommended.

Given the current and projected production capacity, if the U.S. did place a large order for Tamiflu, Roche has testified before Congress that it could be the end of 2007 before they could deliver enough to the national stockpile for 25 percent of the population. Thus, antiviral treatment will only be an effective part of the U.S. response if a pandemic does not occur for several years and, of course, if the pandemic strain is responsive to antiviral medications.

This wll create a real problem for the British: People from other countries will try to sneak into Britain in order to be better protected in case they get sick.

The $58 million the US Congress has appropriated for avian flu preparedness is chump change.

The recently enacted emergency supplemental appropriations legislation made available $58 million for the purchase of influenza countermeasures for the Strategic National Stockpile, including, but not limited to, antiviral medications and vaccines. These funds are most welcome, but TFAH believes that Congress should provide additional funds during the FY 2006 appropriations cycle to continue to build the nation’s antiviral stockpiles from the current level of two percent of the U.S. population to cover a higher percentage of the population.

Does the United States have enough medical supplies to handle a large surge in patients?

Does the National Strategic Stockpile Include ALL Necessary Medical Supplies That Will Be Necessary to Respond to a Pandemic? In addition to stockpiling antivirals and vaccines, when they are available, the U.S. must also stockpile critical medical supplies such as masks, gloves, gowns, bed linens, and all other equipment needed to assure that hospitals and other health care providers are properly protected when the usual supply chain is disrupted either abroad or in the U.S.

Let me answer that question: Of course not! This is all the more reason to avoid getting sick in the first place. If you could go live in a cabin in the mountains for a couple of years and see no one other than those who initially travel there with you then you could avoid getting sick and therefore avoid dying.

We also need an enormous amount of face masks and other paraphernalia that the general population will use to avoid transmission of the pandemic influenza strain in public places.

You might need to wait as long 18 months from the time the pandemic begins before you can be vaccinated against the virus.

Is There a Rapid Response Plan to Develop, Test, and Produce a Vaccine? It will take an estimated six to nine months after a pandemic emerges to develop a vaccine. Questions of how to rapidly review and test the vaccine once it is created remain, including concerns about speeding the approval process by the Food and Drug Administration (FDA), liability protection for vaccine manufacturers, and what type of preservative will be used in the vaccine. In addition, industry representatives have suggested that current production capacity is insufficient to meet the demand for a pandemic influenza vaccine, and that it could take 12-18 months to meet appropriate production levels.26

We need to get beyond the old fashioned fertilized chicken egg technology for growing influenza viruses for vaccines. Newer and faster technologies for making vaccines would go far to reduce the size of the disruption and the number of deaths from a flu pandemic.

We also need better ways to reorganize just about every job and economic function in society so that fewer people have to come in contact with each other while they are working, going to school, going shopping, or receiving services.

If a half million or more Americans were at risk from some type of terrorist attack billions of dollars would be thrown at the problem. We should do the same with the avian flu threat. Avian flu is far more likely to kill you in the next 5 years than anything terrorists might accomplish. Our preparations for it should be commensurate with the scale of the threat it poses.

By Randall Parker    2005 June 27 05:17 PM   Entry Permalink | Comments (11)
2005 June 17 Friday
More Warnings On Avian Flu Danger To Humanity

Foreign Affairs has a series of articles coming out in their July/August 2005 edition on the threat posted by the Avian Influenza H5N1 strain. Michael Osterholm makes the argument that governments have not sufficiently prepared for the possibility of a bird flu pandemic in human populations.

What should the industrialized world be doing to prepare for the next pandemic? The simple answer: far more. So far, the World Health Organization and several countries have finalized or drafted useful but overly general plans. The U.S. Department of Health and Human Services has increased research on influenza-vaccine production and availability. These efforts are commendable, but what is needed is a detailed operational blueprint for how to get a population through one to three years of a pandemic. Such a plan must involve all the key components of society. In the private sector, the plan must coordinate the responses of the medical community, medical suppliers, food providers, and the transportation system. In the government sector, the plan should take into account officials from public health, law enforcement, and emergency management at the international, federal, state, and local levels.

The full articles are not yet available online. But you can read longer excerpts if you click through.

In the same Foreign Affairs issue Laurie Garrett is interviewed on how the avian flu could kill hundreds of millions of people and cause trillions of dollars in economic losses.

Q: If an outbreak does occur, what is the state of preparedness planning between nations, across regions, among departments and ministries of individual governments and throughout the non profit sectors?

Planning is abysmally inadequate, given the likely severity of a pandemic caused by a human-to-human transfer of a virus as virulent as the current H5N1 strain.

Q: Without adequate preparations, what would be the likely toll of such a pandemic globally and in the United States?

The answer depends on the virulence level of the pandemic virus. The 1918 strain, which killed 50 to 100 million people, only killed about two to three percent of the people it infected. The H5N1 strain now in circulation kills 100 percent of the birds it infects and has killed more than 50 percent of the people known to be infected so far. If it manages to mutate into a human-to-human form, and retains even half its current virulence, the death toll would be in the hundreds of millions. The WHO issued a report a few months ago putting the estimate at eight million and has since retracted that estimate, preferring far higher reckonings.

Q: How serious might be the economic, social and political impacts?

One Oxford University computer model, assuming a virus with low virulence, put global losses at two to three trillion dollars. The Oxford team concluded that it is impossible to guess the catastrophic economic toll of a high virulence strain.

Trillions of dollars add up to a serious amount of money. Major killer pandemic have occurred within the lifespan of some people still living. The most famous pandemic in modern times occurred in 1918 with 20 to 50 million killed from a much smaller world population. The avian flu cases recorded in humans to date killed at least half of those infected. A world pandemic of such a lethal strain would make the 1918 outbreak seem mild in comparison.

In a separate article Garrett underscores the unpredictability of avian flu's future path.

According to the March 2005 National Academy of Science's Institute of Medicine flu report, the "current ongoing epidemic of H5N1 avian influenza in Asia is unprecedented in its scale, in its spread, and in the economic losses it has caused."

In short, doom may loom. But note the "may." If the relentlessly evolving virus becomes capable of human-to-human transmission, develops a power of contagion typical of human influenzas, and maintains its extraordinary virulence, humanity could well face a pandemic unlike any ever witnessed. Or nothing at all could happen. Scientists cannot predict with certainty what this H5N1 influenza will do. Evolution does not function on a knowable timetable, and influenza is one of the sloppiest, most mutation-prone pathogens in nature's storehouse.

We do not know the probability for an avian flu crossover into the human population that would develop the abiltiy to cause a massive pandemic. We do not know what the fatality rate would be from such a pandemic. Political leaders have reacted to this uncertainty by doing very little. The public has done the same.

Osterholm points out that food distribution networks do not have large reserves of stored food.

He saved his most flatly worded warning, however, for a news conference organized by the Council on Foreign Relations, which publishes the respected journal. In an interview from Washington following the briefing, he repeated his blunt message of how dire things would be if a pandemic starts in the short term.

"We're pretty much screwed right now if it happens tonight," said Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Osterholm said the "just-in-time" delivery model by which modern corporations operate means food distribution networks don't have warehouses brimming with months worth of inventory.

Most grocery store chains have only several days worth of their most popular commodities in warehouses, he explained, with perhaps 30 days worth of stock for less popular items.

Anthony Fauci says the emergence of a deadly pandemic is just a matter of time.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the threat of a deadly pandemic is growing.

"This is not going to go away," Fauci said during a forum on the issue Thursday at the Council on Foreign Relations. "Get rid of the 'if.' This is going to occur."

Some fairly cheap things could be stockpiled in advance. High quality face masks seem the most obvious. Given that governments look set to fail to make adequate preparations you might want to buy your own stockpile of high quality particulate filtering face masks. On Google Froogle check out 3M N95 models which can go for less than $1 USD per mask when buying boxes of 20 or more. Note that those masks last for only several hours (forget the exact amount of time). A possibly more cost effective choice is the 3M N100 models which cost more but last for 150 hours. The 3M P100 models also last 150 hours.

One drug might help. Seriously consider getting a Tamiflu prescription and store the package unopened.

How and when should I take TAMIFLU?
TAMIFLU should be taken twice daily (once in the morning and once in the evening) for five days. TAMIFLU can be taken with or without food. As with many medicines, if taken with a light snack, milk, or a meal, the potential for stomach upset may be reduced. You should complete the entire treatment of ten capsules, even if you are feeling better. Never share TAMIFLU with anyone, even if they have the same symptoms. It is important that you begin your treatment with TAMIFLU as soon as possible from the first appearance of your flu symptoms.

Tamiflu comes in 10 and 30 tablet amounts. The 10 tablet amount is enough for 1 person. If you are not living alone or have other people you'd want to help in event of an outbreak then keep in mind that the 30 tablet size costs much less per tablet. In the United States you are looking at perhaps $70 to $80 USD for the 10 tablet amount for a single person and perhaps $190 for 30 tablets (and don't skimp by buying from the more questionable online vendors - go brand name). Canadians living in price controlled socialism get to pay less (and get to live off of the labors of market price paying Americans). But once the big crunch comes don't expect to be able to pay even current American prices if you can find Tamiflu at all.

If you think that come a crisis Tamiflu production will rapidly scale up think again. While research a previous post on avian flu I found an expert who claims it would take 18 months to scale up Tamiflu production. Higher demand from governments to stockpile Tamiflu would help make more available. But don't count on governments. If you can afford to then protect yourself and your loved ones.

If you can afford to stockpile food and have the room to store it then buy a lot of dried and canned food. Keep in mind that if you think you are going to eat the food eventually then the money won't be wasted.

If money is no object here is my deluxe version of what to do:

  • Stockpile about 50 or 100 times more Tamiflu than you or your family could use. You can use it to barter if food and other distribution systems break down. Or you can use it to help every friend, acquaintance, and business associate you have. Want to get great deals from a supplier? Give him some Tamiflu and save his life. He'll remember.
  • Stockpile thousands of 3M N100 and P100 face masks. Again, they will make valuable barter material. Or you can give them away to people who do work for you.
  • Stockpile a couple of years of dried and canned food in a dry cool place. I'd also suggest a couple hundred pounds of salmon filets so you can eat healthy even as the supermarkets go empty.
  • Buy a house in the country so that you can avoid contact with other people.
  • The country house should be self sufficient. That means it should have a well, two or three electric generators, and enough fuel to run the electric generators for several months. Photovoltaics in the roof and/or a windmill for electric power would be prudent.
  • If you have to stay in the suburbs make sure you have an extremely well sealed house and high quality filters on air brought in from outside. Though the odds are pretty low you'll get sick from a neighbor's cough.
  • Whether in the country or suburbs make sure your house can function without maintenance for years.
  • Stock your house with whatever else you might need for 2 or 3 years (e.g. seeds and fertilizer for the garden).
  • Be extremely ready to drop everything and isolate yourself with less than a single day's notice. Avoidance of exposure is the best defense. The news says an outbreak is ripping through Tokyo or Shanghai or Calcutta? Time to quit going to work and head for the country or at least stay in your suburban home.
  • If you need to travel to get to a hideaway best to have a lot of gasoline in a small towed trailer to make the trip since you won't want to fly and even exposure at a gasoline station is best avoided (and under panic conditions you can't count on finding gasoline to buy anyway).

Isn't survivalism fun? Though if your country hideaway doesn't have DSL don't expect me to visit.

If you aren't rich but have some money to spend then at least consider some cheaper measures you can take now such as purchase of high quality face masks and Tamiflu. If you live in an apartment with central air you might want to get HEPA air filters for your apartment. If you live in a city but can afford a cheap small piece of country land you could park a cheap travel trailer on it. Don't expect to be able to buy most of these things when the pandemic starts.

If your work lends itself to use of a home office then set one up in advance. Even if your employer does not currently allow working from home make sure you have the basic supplies of a computer, broadband internet connection, and other materials. When a pandemic starts employers will become much more flexible about working conditions than they are now. Any person who can avoid entering the office during a deadly flu outbreak is one less person who might infect the boss.

My guess is that in Western industrialized countries the first year of an avian flu outbreak will bring millions of deaths. But by the second year the mechanisms for how to operate societies while minimizing human-to-human contact will be well worked out. Also, by the second season an increasing number of people will have been vaccinated or will have survived infection. So more people will be able to safely move around and carry out the tasks that involve more human-to-human contact.

The economic and human losses from a highly lethal flu pandemic could be greatly reduced with aggressive advanced preparation by governments and industry. But until the public at large becomes concerned I don't expect governments to do much about it. If biological scientists and medical doctors think this threat deserves greater preparation efforts then a lot more scientists and doctors ought to write op/eds and letters to the editor. Too few people are sounding the alarm. Until that changes you are on your own.

Back during the early Cold War era many people took steps such as building fall out shelters to protect themselves against nuclear war. Today we face a danger whose probability of coming true might well be higher than the chance of nuclear war during the Cold War. Yet few people are taking any steps to protect themselves from a highly lethal pandemic because pandemics do not evoke dramatic images. Infections do not create huge visible blasts. Our buildings and other physical structures are left unharmed by a virus. So governments and individuals do far too little to prevent or defend against a massive killer outbreak that could kill many more people than all the wars of the 20th century.

The other odd thing about the lack of preparation for the avian flu is the larger effort being made to protect against bioterrorism. At this point in time in the year 2005 I think we are at far greater risk from a new natural killer influenza strain produced by Darwinian natural selection than we are from a man made strain produced in a laboratory. Yet in the West we have become so accustomed to controlling and defeating the will of nature that we fear more what other humans can do than what nature can throw up at us. I see this as a premature shift in emphasis. Perhaps 20 years or 30 years from now we will face greater threats from bioterrorism than from natural pathogens. But I think right now we are still living in the twilight of the era when natural selection is more likely than terrorists to produce a new deadly pathogen strain.

Also see the special avian flu articles from Nature.

Nature's editorial on avian flu makes clear they think too little is being done.

If the next pandemic were to arise five years from now, there would have been breathing space to stimulate our drug and vaccine industries to limit the damage it would cause. But that requires urgent action now. As matters stand, a vaccine against a pandemic flu would not be ready until at least six months after a pandemic starts. Too late: by then the worst of the pandemic would already have happened.

A vaccine that can be produced more quickly demands a research effort akin to that for a strategic military weapon, not business as usual. We also need to be able to produce enough of such a vaccine to cope with the surge in demand during a pandemic. At present, the entire world production capacity can produce only enough doses for 450 million people. To stimulate an increase in capacity, we need health policies that boost demand for existing flu vaccines in ordinary years. The same goes for antiviral drugs.

But the worst-case scenario is that a pandemic starts within two years. We would have no vaccine and few drugs, and we would be dependent on governments and the WHO to try to extinguish the first outbreaks at source. That's why the first priority must be to prevent a pandemic emerging in the first place, by extinguishing the disease in animals.

Time for action

Unfortunately, the current situation does not bode well for the abilities of governments and international agencies to cope with this challenge. We should be monitoring in almost real time the genetic changes in the avian and human viruses that could herald the emergence of a pandemic strain, for example. But there is no international funding to help affected countries build decent and sustained surveillance programmes. And while outside researchers want data from affected countries, they aren't engaging enough in the meaningful collaboration needed to build trust and open sharing. The international community is not offering incentives, such as drugs for the Asian countries that would be in the front line of a pandemic. Combine this with the fact that countries are reluctant to share the few data they have because their analysis could affect their trade and economies, and the current mess in surveillance is hardly surprising.

If I was King I'd allocate $20 billion per year in the United States for preparations against avian flu. But I'm not King and neither is anyone else. So instead I'll just give you my warning: We ought to do orders of magnitude more than we are currently doing to get ready for the next highly lethal influenza outbreak, whenever it might come.

By Randall Parker    2005 June 17 04:42 PM   Entry Permalink | Comments (56)
2005 April 13 Wednesday
Dangerous 1957 Influenza Strain Accidentally Sent To Thousands Of Labs

What, me worry?

A dangerous strain of the flu virus that caused a worldwide pandemic in 1957 was sent to thousands of laboratories in the United States and around the world, triggering a frantic effort to destroy the samples to prevent an outbreak, health officials revealed Tuesday.

Because the virus is easily transmitted from person to person and many have no immunity to it, the discovery has raised alarm that it could cause another deadly pandemic if a laboratory worker became infected, officials said.

...

The virus, known as an H2N2 strain, killed one million to four million people worldwide in 1957 and 1958, including about 70,000 in the United States.

The world population is a lot bigger today. So the potential death toll from outbreak of the same strain could be much higher.

Meridian Biosciences distributed the virus in order to give labs a strain to use for practice testing for flu.

In this case, the kits and samples were designed for groups that assist labs with proficiency testing. Dr. Jared Schwartz, an official with the College of American Pathologists, said Meridian was told to pick an influenza sample and chose from its stockpile the deadly H2N2 strain, which it had received from a "germ library" in 2000.

The College of American Pathologists has said it sent 3,747 kits to various U.S. labs.

At the moment I'm writing this the Meridian Bioscience web site is suspended. My guess: A rarely visited web site was suddenly swamped by a huge number of visitors coming to see what Meridian has to say about their potentially deadly error.

If an outbreak does not happen as a result of this error we might benefit in the long run from the publicity surrounding the error. There is an obvious question that ought to be asked at this point: Which other companies, academic, and government labs already have the 1957 strain or other past killer influenza strains? If you would have asked me before this story broke to guess at how many organizations had the 1957 H2N2 strain I would have guessed a few government labs and maybe a couple of academic labs. Now I'm guessing at least hundreds of labs already had it even before Meridian's latest distribution. The same applies to other past killer strains.

Meridian and the World Health Organization think the risk of outbreak is low.

"While a few H2N2 laboratory acquired infections have been documented in the past, the likelihood of laboratory-acquired influenza infection is considered low when proper biosafety precautions are followed," Meridian said in a statement. "The risk for the general population is also considered low." The WHO also has said the risk of an outbreak is slight.

Klaus Stohr of the World Health Organization says that the CDC doesn't classify this pathogen as so dangerous that its distribution should be restricted.

Stohr said the company which sent out the virus samples - Meridian Bioscience Inc. of Newtown, Ohio - abided by current U.S. regulations.

"At the moment, H2N2 is classified as a BSL2, or biosafety level 2, pathogen," he said. "They are allowed to (send it out as part of a test kit).

"They sent it properly packaged, they informed the recipient, they only became aware after the whole matter was better understood that (the U.S. Center for Disease Control and Prevention) is working on a change in the biosafety level for H2N2."

This error was not discovered quickly or reacted to quickly.

The virus samples were distributed by the CAP in October 2004, but the problem was discovered only by a Canadian laboratory only last month.

So the virus was sitting in labs for 5 months, was discovered last month by a Canadian lab (good for them!), and only now is the word going out to destroy the samples. One can argue that labs which get these sorts of samples follow all sorts of safety procedures. But don't you think those lab workers would be more diligent (if not to say scared) if they were made aware that they were receiving a influenza virus that has more lethality than the average strain?

Coincidentally, a great vaccine developer and the man who led the development of the original vaccine for the 1957 Hong Kong flu strain has just died.

Maurice Ralph Hilleman, 85, whose vaccines probably saved more lives than any scientist in the past century, and whose research helps the medical establishment predict and prepare for upcoming flu seasons, died April 11 of cancer at Chestnut Hill Hospital in Philadelphia.

Dr. Hilleman created eight of the 14 most commonly used vaccines, including those for mumps, measles, chicken pox, pneumonia, meningitis, rubella and many other infectious diseases. He developed more than three dozen vaccines, more than any other scientist. His measles vaccine alone is estimated to prevent 1 million deaths worldwide every year.

This article on Hilleman makes him sound like an unusually independent, creative, and driven mind:

He discovered Darwin in eighth grade and was caught reading "The Origin of the Species" in church.

He reminds me of similar unknown, Norman Borlaug, whose work developing crop strains has saved more people from hunger than any other person in history.

By Randall Parker    2005 April 13 12:13 PM   Entry Permalink | Comments (1)
2005 April 09 Saturday
Drug Resistant Staph Spreading Into General Population

Staphylococcus aureus or staph is a bacteria that occasionally causes deadly infections. Methicillin-Resistant Staphylococcus Aureus or MRSA is a strain (or probably a group of strains) of staph that are resistant to many antibiotics. For a long time MRSA and other resistant strains were rarely found outside of hospital settings. Now a new article published by CDC researchers in the New England Journal of Medicine reports that drug resistant staph is increasingly being found in people who have no obvious connection to hospitals or other risk factors.

Overall, they found 17 percent of drug-resistant staph infections were caught in the community and did not have any apparent links to health-care settings.

"Close to one-fifth of what used to be a hospital-specific problem is now a community problem. And that's a large number," said the CDC's Dr. Scott K. Fridkin. "We didn't think it would be anywhere near that high when we started the study."

The drug resistant strains have become more robust.

The CDC researchers checked up to two years of lab reports for drug-resistant staph. More than 80 percent of the 12,553 cases were excluded because the patients had been hospitalized, had a history of surgery or dialysis or had another risk factor.

About 17 percent overall, or 2,107 cases, were determined to be community-acquired staph. The rate was 20 percent in Atlanta, 12 percent in Minnesota and 8 percent in Baltimore.

"When they got out in the community, it was felt these strains weren't strong enough to make it on their own. That no longer appears to be the case," said Dr. Henry F. Chambers of the University of California at San Francisco, who wrote an accompanying editorial.

Those cases are from a small number of cities for 2001 and 2002. The national figure is much higher. MRSA causes 130,000 people to be hospitalized per year.

Previously, MRSA was seen only in the hospital in patients with underlying diseases or compromised immune systems. Now the organism appears to be common among people everywhere, including those in communal settings such as the military, prisons, daycare facilities, and on athletic teams. The CDC estimates that roughly 130,000 people are hospitalized with MRSA each year.

This state of affairs is the result of decades of overuse of antibiotics. Natural selection has produced mutations to allow bacteria to resist many different antibiotics. Bacterial infections are starting to get scary again. Worse yet, the MRSA strains of staph could be stopped with Vancomycin. But Vancomycin resistant staph (VRSA) is believed to be spreading rapidly.

For years, the best treatment for MRSA was the powerful antibiotic vancomycin. But even this weapon has failed against new strains of staph that have emerged. Some infectious-disease experts predict that by 2010, 40% of staph infections will be vancomycin-resistant. And for the moment, there are few alternatives. Cubist Pharmaceuticals Inc. (CBST ) in Lexington, Mass., won approval in September for a new type of antibiotic, Cubicin, that works as well as vancomycin against staph. But experts figure it’s only a matter of time before the bug learns to evade Cubicin, too.

Worse yet, previously the "flesh eating" (really flesh killing) disease necrotizing fasciitis was caused mainly by strep. But now staph is developing the ability to spread rapidly in skin even as it develops the ability to resist a larger set of antibiotics.

In a separate article in the journal, researchers reported that they had linked drug-resistant staph infections to a rare, often-deadly disease known as necrotizing fasciitis, or more commonly, "flesh eating" syndrome.

"Necrotizing fasciitis is a terrible disease, but before now, Staph aureus was never the cause," said Dr. Robert Daum, a pediatrics professor at the University of Chicago and one of the first physicians to notice wider circulation of drug-resistant staph.

Surgeons cut large chunks of skin off of people suffering from drug-resistant necrotizing fasciitis. Even amputations of extremities are necessary in some cases. Sometimes the people survive badly scarred. Other times they die anyway.

In the United States tens of thousands of people die per year from infections that they picked up while hospitalized.

For example, with a hospital infection rate of 5%, of which 10% are bloodstream infections, and an attributable mortality rate of 15%, 26,250 deaths can be directly linked to nosocomial bloodstream infections. However, if a 20% attributable mortality rate is assumed, the number of deaths is from 17,500 (with a 2.5% nosocomial infection rate) to 70,000 (with a 10% total nosocomial infection rate).

Drug-resistant bacteria might be killing more people per year than are killed by car accidents. If that is not the case now it might be the case 5 years from now - barring either big advances in techniques to avoid infection or the development of better antibiotics to use on infected patients.

Meanwhile the US Food and Drug Administration (FDA) is using trailing edge benchmarks to test the efficacy of new antibiotics.

Another obstacle to drug development is the increased regulatory requirements for antibiotics. In the early 1990s, the FDA introduced guidelines that resulted in new and costly demands for the development of antibiotics.7 In an era when hospital- and community-acquired infections are increasingly drug resistant, the efficacy of new drugs are benchmarked against susceptible strains, such as methicillin-susceptible Staphylococcus aureus.

An FDA advisory board has stated that novel antibacterial agents, to be considered for approval, should demonstrate frank superiority to existing antibiotics.6 However, innovative products that fight drug-resistant strains are unlikely to be better than existing drugs that can effectively treat susceptible strains. New antimicrobials would be more likely to make it to market if the FDA introduced new references, such as drug-resistant strains of bacteria, and used new pathogenic targets to evaluate efficacy, such as the inhibition of toxins or prevention of biofilms.

Why should the FDA measure efficacy of new antibiotics against strains that are not antibiotic-resistant? Isn't the biggest need for new antibiotic drugs due to the development of resistant strains of bacteria?

Also, why should the FDA require that new antibiotics be better than existing antibiotics? What is wrong with allowing new competitors that are no better than existing choices? Keep in mind that some people are allergic to or otherwise react adversely to multiple antibiotics. They need more choices.

Think help is on the way in the form of new antibiotics? Don't count on it. Many drug companies have decreased or ended their efforts to develop new antibiotics.

Part of our problem is due to the overuse of antibiotics for humans and also in agriculture. Antibiotics derived from natural sources such as the penicillin family found in a mold have been used so much that resistant strains are now quite common. It is harder to develop an antibiotic totally from scratch. But another obstacle is the FDA. This problem is unlikely to be fixed until the yearly body counts from bacterial infections in the United States get much larger. The public fears dangerous drugs and generally wants more regulation, not less.

By contrast, Tyler Cowen points to a recent post by Bryan Caplan (and these four guys I'm mentioning are all economists) who reports on work by Dan Klein and Alex Tabarrok on how economists see the FDA.

What happens, however, if we listen to economists who specialize in the FDA, rather than random economists at the AEA? Klein reports that opposition becomes very one-sided indeed:

Alexander Tabarrok and I review much of the literature in our website “Is the FDA Safe and Effective?” (FDAReview.org). We include a compendium of 22 quotations by economists calling for significant liberalization of FDA control, and we explain that we have been unable to find quotations favorable to current levels of control by economists who work on the FDA. I believe economics reaches a clear conclusion in favor of significant liberalization of FDA control of pharmaceuticals. Thus, given the range of response options provided by the question, the first two options [strongly support/mildly support] are simply wrongheaded.

Bottom line: The public thinks the FDA is great. Regular economists think it's pretty good. And economists who specialize in the FDA think it's pretty bad. I think I see a familiar pattern.

To address the problem of drug resistant antibiotics We need:

  • a better regulatory environment to allow more antibiotics to make it to market.
  • more basic research on bacteria.
  • less use of antibiotics in cases where only viruses are involved.
  • better practices in hospitals to reduce the spread of pathogens to patients.

Stay well rested, well nourished, healthy, and away from hospitals. Wash your hands and body after exposure to others - especially after contact sports. Also, don't go visiting someone in the hospital if you have even so much as a cold.

By Randall Parker    2005 April 09 12:52 AM   Entry Permalink | Comments (23)
2005 March 25 Friday
Caterpillar Cells May Accelerate Flu Vaccine Production

Caterpillar cells and genetically engineered bacilovirus might provide a better means to make influenza vaccines.

BALTIMORE, MD -- March 21, 2005 -- Using a strategy involving a genetically modified baculovirus and caterpillar cells scientists from Protein Sciences Corporation have been able to speed up a key step in the development of an experimental cell-based influenza vaccine. They report their findings today at the 2005 American Society for Microbiology Biodefense Research Meeting.

"The bird flu may become the next flu pandemic strain. It could happen at any time," says Keyang Wang, a scientist at Protein Sciences Corp. and a researcher on the study. "The most effective method to control such an outbreak is the widespread use of a vaccine. The traditional egg-based method requires 3 to 6 months to develop the vaccine. With our cell-based method, the time from receipt of the virus strain to the final vaccine product would be shortened to approximately 1 to 2 months."

Wang is absolutely correct to state that the current chicked egg-based method for manufacturing vaccine takes a long time. Plus, it can not easily be scaled up quickly. Should a big killer influenza strain break out into human populations existing vaccine manufacturers would be hard pressed to produce billions of doses of influenza vaccine. My guess is they would be able to satisfy only a small fraction of the demand for vaccine.

The existing approach for making vaccines in eggs might not work with a killer avian influenza strain. The egg embryos might be killed by the virus before much vaccine could be produced.

Today's flu vaccines are prepared in fertilized chicken eggs. The eggshell is punctured, and the influenza virus is injected into the fluid surrounding the embryo. The egg is then resealed, the embryo becomes infected, and the resulting virus is then harvested, purified and used to produce the vaccine. In addition to the long development time, another drawback to this method is the possibility that an avian influenza virus would be lethal to embryos in the eggs.

The vaccine strategy pursued by Protein Sciences, known commercially as FluBlok, does not rely on whole vaccine virus. It uses a purified concentration of a key molecule on the surface of the virus, called hemagglutinin, to elicit an immune response against that specific strain of the virus.

Wang and his colleagues have developed a methodology for rapidly producing and purifying hemagglutinin from an influenza virus. They extract the genes responsible for the production of hemagglutinin from the virus and insert them into a baculovirus. Caterpillar cells are then infected with the virus and begin to produce the hemagglutinin.

The FluBlok vaccine has recently finished phase II clinical trials, where it has established safety and the ability to elicit a strong antibody response in humans.

"Since all the media used here are chemically stable and commercially available, the process can be easily scaled up for commercial manufacture," says Wang. "New FluBlok vaccines can be developed quickly and safely to address late appearing influenza viruses and to reduce the impact of a potential flu pandemic."

It is interesting to note that this vaccine is being developed by a commercial company. The US government and other governments have been slow to respond to the need for vaccines that can be manufactured more rapidly and for which manufacturing can more easily be scaled up. Both capabilities are needed in order to produce large numbers of vaccine doses should a major killer influenza strain become established in human populations. With that thought in mind it is worth looking at more of what Protein Sciences has to say for itself.

The FluBlØk™ vaccine may even provide more protection than current commercially available vaccines.

FluBlØk™, derived from Recombinant hemagglutinin (rHA) is a patented replacement vaccine for the current licensed vaccines that are produced in eggs using 40-year old technology. FluBlØk™ consists of three rHA proteins corresponding to the flu strains selected by the World Health Organization and the Center for Disease Control for each year's vaccine. These proteins are produced in serum free insect cells and formulated in PBS without preservatives or adjuvants. Clinical trials have shown safety and efficacy in healthy adults and the elderly population:

  • Several Phase I and II trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID) involving over 600 subjects demonstrated safety and efficacy as reported in four published studies in the Journal of Infectious Diseases. A significantly higher percentage of elderly subjects receiving a higher dose of our vaccine develop protective antibody titers compared to the licensed vaccine.

If this vaccine lives up to its claims it will both work better and be faster and easier to manufacture.

This vaccine is made using a virus to infect caterpillar cells grown in culture.

There are many advantages of using the baculovirus expression system, including: high expression levels, limitless size of the expressed protein, efficient cleavage of signal peptides and processing of the protein, post-translational modifications and simultaneous expression of multiple genes. In addition to these advantages, expressed proteins are correctly folded and biologically active. Human clinical studies have demonstrated that proteins produced in the baculovirus expression system can be safely administered to humans. Because the cells die during the manufacturing process, the BEVS system is uniquely able to produce proteins from genes of unknown function.

If you page down to the bottom of that list link you'll see a graphical chart comparing how this vaccine production method compares to several other vaccine production methods in terms of speed, cost, glycosylation (coating of virus antigen proteins with sugars that would be found on them naturally), folding (vaccine proteins have folded 3 dimensional shapes that need to be duplicated), and ease of FDA approval.

I wish these folks luck in their attempts to bring their vaccine to market. We'd all be better off with an influenza vaccine that can be made more rapidly and cheaply and which even elicit a stronger immune response. This vaccine may even save many of our lives some day.

By Randall Parker    2005 March 25 04:30 PM   Entry Permalink | Comments (2)
2005 March 10 Thursday
More Signs Bird Flu Is Spreading Between Humans

The World Health Organization is reporting cases where multiple members of families are testing positive for bird flu. When multiple infections occur in the same family that raises the threatening possibility that the bird flu is mutating into a form that is more capable of human-to-human transmission. The development of that capability could ignite a deadly worldwide bird flu pandemic which could potentially kill tens of millions of people. Some of the bird influenza cases being found in Vietnamese families are strongly suggestive that human-to-human transmission is taking place.

Since the family members are infected with identical or closely related H5N1, distinguishing between a common source and human transmission is heavily dependent on onset dates. Most cases show symptoms 2-4 days after exposure. Therefore, cases involving a common source will develop symptoms at about the same time. If the transmission is from one family member to another, there will be a longer time lag and the onset dates will be bimodal.

As noted above, the latest familial cluster from Thai Binh has a 7 day differential between onset dates suggesting the sister was infected by her brother.

Since primary caregivers for sick family member are most often female another sign of human-to-human transmission is the higher rate of infection of females in cases where multiple family members are diagnosed with bird flu.

However, another way to demonstrate human-to-human transmission in these other familial clusters is to simply compare the gender distribution of the primary cases relative to the secondary. There were 13 index cases in the 12 clusters (in one cluster cousins developed symptoms at the same time). There were 6 females and 7 males indicating the risk to both sexes was similar. In contrast, 11 of the 14 secondaries were female.

Why should we be alarmed by these reports? Karl Nicholson, a professor of infectious diseases at University of Leicester in Britain who currently working on bird flu vaccine development says bird flu has a very high mortality rate.

Based on the current recognized cases of the illness, it seems to have an 80% mortality rate, says Nicholson.

Imagine a virus with such a high mortality rate mutating to become easily transmissible between humans.

However, the mortality rate from bird flu may be overstated due to cases that are not diagnosed.

The World Health Organization said Tuesday that seven Vietnamese patients who initially tested negative for bird flu have been found to be carrying the virus after their samples were retested.

All seven, who were first tested in January, have since recovered, said WHO regional spokesman Peter Cordingley.

Still, even if some of the current estimate for bird flu mortality rate is overstated it is very unlikely to be overstated by, say, a full order of magnitude.

A recent case with a Vietnamese male nurse is another possible case of human-to-human bird flu transmission.

A 26-year-old male nurse from northern Vietnam who provided bedside care for a 21-year-old bird flu patient now in critical condition has himself tested positive for H5N1 avian influenza, according to media reports from the region.

It is possible the nurse was exposed to the patient's blood or mucus. It is not clear that the nurse got the virus from the patient and even if he did it is not clear that the virus was transmitted by a route that would mean the virus has developed greater ability to move between people.

Whether or not these cases indicate the avian flu is now more able to spread between humans the virus is still over there moving through duck, chicken, and other bird populations. It may still mutate into a massive killer pandemic.

Should the bird flu break out into the general population keep in mind that in my past posts I've listed things we ought to do to reduce our risks of getting the flu in the case of a killer pandemic. If I don't turn out to be one of the early victims when the pandemic starts I'll colllect together all those items and you all can then read my comprehensive list of things you ought to do and ought not do.

One thing you ought to do now: Tell your government to accelerate the development of better flu vaccine production technologies so that when a killer pandemic eventually shows up in the human population we will be able to more quickly and massively manufacture vaccines.

By Randall Parker    2005 March 10 01:37 PM   Entry Permalink | Comments (4)
2005 February 22 Tuesday
Avian Influenza May Mutate Into Killer Human Pandemic

Public health officials are starting to sound downright scary in their pronouncements about the potential danger to humans of the H5N1 influenza strain which is spreading through populations of chickens, ducks, and other birds in Southeast Asia. Julie Gerberding, head of the US CDC, told a meeting of the American Association for the Advancement of Science (AAAS) that we are probably in a period equivalent to the historical period right before the 1918 influenza pandemic which killed tens of millions of people.

In an address to the AAAS Annual Meeting in Washington, D.C., Dr. Julie Louise Gerberding noted that the in its current form poses a relatively limited problem for humans. But, she said, the current situation "probably" resembles the period before the 1918 Spanish flu outbreak when the virus was quietly mutating into a strain that would eventually leave 50 million people dead.

"Most people who are looking at this recognize it is a very ominous situation for the globe in terms of statistical probability" of a larger outbreak among humans, Gerberding said.

Gerberding's comments Monday came just a day after Dr. Nancy Cox, the CDC's chief influenza scientist, suggested to a AAAS audience that further mutation in the avian flu in Asia could precipitate the worst pandemic in human history.

Researchers believe that prolonged contact with infected birds or consumption of raw, infected chicken meat is required for the virus to jump to humans. But once it does make the jump, it appears to be lethal: According to a report Monday in the Financial Times, the current outbreak has infected 55 humans in Asia and killed 42, a mortality rate of 76 percent.

There is some question as to whether the bird flu really does kill three quarters of the people it infects. If more people are being exposed but developing symptoms too mild to be diagnosed as bird flu then the reported deaths might represent a smaller fraction of a much larger number of infected. Dr. Cox says people who may have been exposed to the bird flu are being tested for immune responses to the flu virus as a way to determine if they managed to have mild cases of bird flu.

"Some studies are going on to get a better handle on what the real case fatality case is," she said. For example, poultry workers exposed to the virus would be checked for any H5N1 antibodies in their blood.

However, some of the previously undiagnosed human cases of bird flu infection appear to have been fatal. The disease may be occurring more often in humans than previously expected but without typical influenza respiratory symptoms.

Two Vietnamese children who died in 2004 of diarrhoea and apparent encephalitis actually had H5N1 bird flu, British and Vietnamese scientists have reported.

The cases raise the frightening possibility that there have been far more human infections with H5N1 than thought, because many cases have been overlooked by doctors watching for the fever and cough of typical flu.

The cases of the Vietnamese children suggest that other cases of bird flu are not being diagnosed.

Dr. Menno de Jong, with Oxford University's Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, said he and fellow researchers believe the boy's case, which wasn't linked to bird flu until months later, may mean that other cases with no respiratory symptoms have gone unnoticed.

The discovery of these H5N1 bird flu cases in the two children was accidental because some scientists happened to be investigating the causes of encephalitis (brain inflammation) in southern Vietnam and found the bird flu link.

One complicating factor in any analysis of antibodies to H5N1 influenza strains is that earlier and far less lethal strains of H5N1 provoked immune responses a few years ago that will show up in tests for H5N1 infections today. Yet the H5N1 of today appears to be much more lethal than the strains from 5 years ago.

Well dear reader, should you be worried about this? I think so. I would not be the least bit surprised if later this year or in 2006 or 2007 tens of millions of people died worldwide from a further mutated strain of the H5N1 bird flu. All it would take would be for that bird influenza virus and an influenza virus from humans to infect an animal or human at the same time. Then the two strains could have their DNA recombined into a strain that has the deadliness of the avian flu and the transmissibility of a human flu. The result would be a pandemic in which each of us would lose family members, neighbors, and friends.

We desperately need more rapid ways to make and scale up the production of influenza virus vaccines. The current method of growing influenza viruses in fertilized chicken eggs for months is too slow and does not scale up rapidly. But when an influenza strain with high human lethality finally springs up we are not going to have a year or two to get ready.

CDC officials are not alone in sounding the alarm about bird flu. Joseph Domenech, director of animal health at the United Nations Food and Agriculture Organization (UN FAO), says the H5N1 avian influenza is a sword of Damocles hanging over the world.

"The time is ripe today for the international community to see how the virus constitutes an enormous sword of Damocles in terms of public health and the rural economy," Domenech told AFP during an interview.

The World Health Organization thinks wealthier governments should stockpile vaccine against H5N1 bird flu.

Governments should consider stockpiling vaccine against H5N1 bird flu now, before a pandemic starts, a World Health Organization report out next month will advise.

The change in policy reflects growing fears that an H5 pandemic is likely, and that there will not be time to produce much vaccine once it starts. "When we realised H5N1 is not going to be eradicated in poultry in Asia for at least another couple of years, that made the risk of H5 much higher," Klaus St�hr, head of the WHO's influenza team, told New Scientist.

That story reports that the United States government plans to stock 4 million doses. With a new strain of flu 2 doses are required for full immunity. So those 4 million doses are even more inadequate than they initially appear to be. As for the rest of the world, France and Italy are going to stockpile a couple million doses each.

If a pandemic with high rates of lethality breaks out then I predict a black market in the vaccines that are available against the virus.

Two companies have developed pilot batches of vaccine against H5N1 influenza virus.

Two companies, Sanofi Pasteur and Chiron Corp., are currently under contract to make H5N1 vaccines for the United States. Each company received a contract in May 2004 to make small pilot batches. In September, Sanofi (formerly Aventis Pasteur) received a contract to make 2 million doses. US officials have said that clinical trials of those vaccines are expected to start soon. Chiron is also under contract to make 40,000 doses of an H9N2 vaccine, another flu strain regarded as having pandemic potential.

A Chinese team has also developed a vaccine against H5N1 influenza. But the initial development of a vaccine is not the hard part. The hard part is scaling up vaccine production to make doses for billions of people.

If and when a big killer bird flu crosses over into humans the most rational response should be to find ways to greatly reduce human-to-human contact while we wait for vaccine production to be scaled up. We will need to radically alter our lifestyles for a year or two while waiting for vaccines to be produced for billions of people.

By Randall Parker    2005 February 22 01:27 AM   Entry Permalink | Comments (77)
2004 December 15 Wednesday
Rapid Vaccination Could Theoretically Stop A Flu Pandemic

But there is the problem of where to get billions of vaccine shots in a hurry.

If a flu pandemic similar to the deadly one that spread in 1918 occurs, it may be possible to keep the pandemic in check through vaccinations, a new study suggests. The infamous 1918 pandemic killed up to 40 million people worldwide, but the virus strain was not unusually contagious compared to other infectious diseases such as measles, according to a new analysis by researchers at Harvard School of Public Health. However, the 1918 flu was quite lethal once contracted, believed to be 10 times more lethal than other pandemic strains.

Epidemiologists analyzed historical epidemic data in 45 US cities and found that the transmissibility of the 1918 strain as measured by the number of people infected by a single case was only about 2 to 4, making the strain about as transmissible as the recent SARS coronavirus. Since people with influenza can transmit the infection before the appearance of symptoms, strategies for transmission reduction, including vaccination, would need to be implemented more rapidly than measures for the control of the recent SARS outbreak. Isolation methods alone, such as those used for controlling SARS, would not be effective.

The analysis, "Transmissibility of 1918 Pandemic Influenza," by Christina Mills, doctoral student in the HSPH Department of Epidemiology, and faculty co-authors appears in the Dec. 16, 2004 issue of Nature.

World Health Organization officials have warned that we are closer now to another pandemic than in any other recent time because of the persistent bird flu epidemic in East Asia that threatens to jump to humans.

"Our study suggests that if you could vaccinate a reasonable number of people before exposure, a future flu epidemic could be controlled," said Mills. "But flu takes just a couple of days to become contagious in a person, unlike the almost week-long latency period we experienced with SARS. Isolation would be only partially effective. Rapid vaccination is essential."

"Before this study, estimates were all over the map on the transmissibility of pandemic flu," said co-author Marc Lipsitch, associate professor of epidemiology at HSPH. "Some thought it was so transmissible that vaccines would be unlikely to stop it. This study is optimistic, except we don't have the vaccine. It is now even more important to put resources into the development of vaccine technology, manufacture and distribution systems to make possible a rapid response to the next outbreak of an entirely new flu strain."

The problem with rapid vaccination as a response to a new strain with pandemic potential is that it takes 6 months to make a vaccine for a new virus strain and then the whole world has a capacity to make only 300 million doses. Worse yet, a completely new strain would require two doses per person for full immunity. We need vaccine manufacturing technology that is faster and more easily scalable.

In event of the emergence of a really dangerous flu strain as things stand now we aren't going to get vaccines quickly enough to prevent the spread of the virus. Therefore societies would need to be quickly reorganized and rearranged to reduce the rate of transmission of flu viruses. People would need to make many changes to how they carry out their daily routines in order to reduce the risk of exposure to influenza.

By Randall Parker    2004 December 15 11:08 PM   Entry Permalink | Comments (1)
2004 November 29 Monday
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.

By Randall Parker    2004 November 29 11:19 AM   Entry Permalink | Comments (15)
2004 October 28 Thursday
1918 Killer Flu Virus Research Lab Containment Levels Too Low?

The 1918 influenza virus pandemic that killed tens of millions of people is being reconstructed in research laboratories using virus samples extracted from the long frozen bodies of victims of the virus who were buried in very cold regions of far northern Europe. While some of the work on these virus samples were done in a top level BioSafety Level 4 (or BSL-4 or BSL4) level laboratory much of the work on the 1918 influenza is being done in lower level BSL-3Ag and even lower level BSL-3 labs. (same article here)

Yet despite the danger, researchers in the US are working with reconstructed versions of the virus at less than the maximum level of containment. Many other experts are worried about the risks. “All the virologists I have spoken to have concerns,” says Ingegerd Kallings of the Swedish Institute for Infectious Disease Control in Stockholm, who helped set laboratory safety standards for the World Health Organization.

If a virus that killed 40 million people is not worthy of being handled in top level of containmen then what is? I guess an argument can be made that smallpox is an even greater threat and warrants an even higher level of caution. But I'm not even sure that is true. My guess is we are far better equipped to stop a smallpox outbreak than to stop an influenza outbreak.

By contrast, the team in Georgia, the first to experiment with genetically engineered 1918 viruses, did all its work at BSL-3Ag. Meanwhile, Michael Katze at the University of Washington at Seattle is planning to expose monkeys to aerosols of 1918-type viruses at BSL-3, a step down from BSL-3Ag. The recent SARS escapes were from BSL-3 labs.

Some scientists are less worried that the bioengineered viruses being worked with are that big of a potential threat.

The head of the World Health Organization's global influenza program said he isn't certain that work on the virus needs to be restricted to the most secure facilities, but the agency would be open to hosting a forum on the issue.

"What we mustn't forget is that what they're working on is not the 1918 virus," Dr. Klaus Stohr cautioned in an interview from Geneva.

The 1918 flu epidemic (sometimes called the Spanish flu though it probably didn't originate in Spain) killed somewhere between 20 and 40 million people. The estimates of mortality are broad because there are no reliable statistics on deaths in much of the world and death rates in differed greatly. But an assumption that about 2% of the world's population died is not unreasonable. My guess is that an influenza outbreak that happened today with similar mortality rates would probably kill between 60 million and 150 million people. Of course in the more developed countries public health mesures such as quarantines and protective gear would reduce the death rates considerably. Yet most people do not live in developed countries. Also, after the first season of outbreak a vaccine might be able to be produced that would halt it in at least parts of the world.

Currently a building boom in BSL-3 and BSL-4 labs is underway mainly in reaction to the 9/11 terrorist attack and the anthrax attack that followed it.

Altogether, the nation's combined total of BSL-4 lab space, 1,689 square meters, "is extremely limited and obviously insufficient," says Stephen Morse, director of Columbia University's Center for Public Health Preparedness. To remedy such shortages, NIAID awarded grants of about $120 million each in October 2003 to help pay for new BSL-4 labs at Boston University and a second, much larger lab at UTMB. Together they will add 3,925 square meters, more than twice the current amount of space.

In addition, NIAID is planning to build two BSL-4 labs for its employees, one in Hamilton, Montana, (which is now undergoing an environmental assessment) and the other in a new National Interagency Biodefense Campus at USAMRIID. They will add 2,879 square meters, almost twice as much as exists now. In addition, the CDC plans to build 1,275 square meters of new BSL-4 space in Atlanta.

But all those labs take 5 to 10 years to become available.

We need for scientists to figure out what made the 1918 so deadly. Another influenza strain could mutate into that level of lethality at any time. Would convention influenza vaccine development techniques work against the 1918 strain? We need to find out. So the research work is very much worth doing.

An important aside to this report is that we need more rapid techniques for making influenza vaccines. The latest problem with contamination of 48 million doses of Chiron Corporation's influenza vaccine highlight the problem with the current method of making influenza vaccines in specially produced chicken eggs. Influenza vaccine production takes 6 months and can not easily be scaled up to handle a known large scale outbreak.

The quaint system of producing flu vaccine based on seasonal egg-laying has harsh implications for what would happen if new batches had to be made in a hurry to fight a super-strain pandemic. At best, it would take half a year.

We need very rapid techniques for producing flu vaccine.

It is only a matter of time before a new highly deadly flu strain arises that rivals or surpasses the 1918 pandemic in deadliness.

Monica Schoch-Spana, a senior fellow at the Center for Biosecurity of the University of Pittsburgh Medical Center, said the likelihood of an upcoming flu pandemic is "not a matter of if, but when."

Also see my previous post Sequencing Of 1918 Spanish Flu DNA Increases Risk Of Bioterrorism.

By Randall Parker    2004 October 28 04:20 PM   Entry Permalink | Comments (9)
2004 February 02 Monday
Bird Flu Virus Outbreak Has Infectious Disease Experts Worried

The A(H5N1) strain of avian influenza that has spread to many Asian countries and caused 7 deaths out of 11 known human cases has a lot of disease experts on edge. The fear is that the avian virus and the human H3N2 strain currently spreading in Asian could coinfect either a human or a bird and the avian and human viral DNA could recombine in the same infected cell to create a new virus strain that could spread rapidly in humans with fatal results. A World Health Organization (WHO) official says a combined human/avian flu strain could kill millions worldwide.

Shigeru Omi, director of the UN agency's Western Pacific office, warned last week that millions of people around the world could die if the H5N1 strain of bird flu mixes with the human H3N2 virus that was headed towards Asia.

The fear is for a reprise of the 1918 flu pandemic which killed 1% to 2% of the world's population.

Dr. Klaus Stöhr of the WHO says so far the pattern of human cases of bird flu fit the previous patterns of bird flu outbreak in Hong Kong.

Because the virus apparently "vanished" after causing the cluster of infections, Dr. Stöhr said, his agency does not consider the possible person-to-person spread a major public health threat. Similar transmission, limited to a short chain of people and with a definite end, occurred in earlier avian influenza outbreaks in Hong Kong, he said.

The fact that the bird flu virus has not rapidly spread from existing human cases suggests it hasn't mutated yet to be easily spreadable in humans.

The fact that just a handful of human cases have been reported this time despite the bird flu being around for several weeks was also fairly encouraging.

Government cover-ups and insufficient testing have allowed bird flu to spread for months before being detected.

W.H.O. first learned about the mutated A(H5N1) strain in January through reports from Vietnam, then learned that birds had begun getting infected elsewhere in Asia as early as April 2003. In addition to Vietnam, the affected countries are Cambodia, China, Indonesia, Japan, Laos, South Korea and Thailand. "We have no clue which species of bird first spread it," Dr. Stöhr said.

Better surveillance procedures are needed in many countries. Plus, there is not enough money to kill the chickens in countries where the bird flu is spreading. This increases the chance that bird flu viruses will combine with human viruses to produce a virus capable of killing millions in a human outbreak.

All flu viruses probably originate in birds, and the best environment for making the jump to humans is one where densely packed people live closely with birds and animals.

"In Asia we have a huge animal population, a huge bird population and two-thirds of the world's people living there,'' said Klaus Stohr, chief influenza scientist at the World Health Organisation.

The population of China alone is bigger than that of the whole of Africa, and 80 percent of the new human flu strains the last few decades appeared in China first.

Growth in egg and chicken consumption in Asia has increased the capacity of chickens to be hosts for avian influenza strains.

From the early 1970s to the early 1990s, per capita consumption of meat, eggs and milk grew about 50 per cent in developing countries, leading to big increases in animal herds. Over the last 25 years, the fastest growth has been in the numbers of chickens and pigs, the FAO says.

Asians' fondness for shopping at live animal markets also adds to the chances for flu jumping species, experts say.

The problem with vaccines is that they take too long to develop and manufacture. The method of growing vaccines in eggs takes months and requires that large numbers of the proper kinds of eggs and egg-growing facilities be available. It simply is not possible to scale up that quickly and it takes months to do so. Even worse, bird flu poses a special difficulty because unmodified avian influenza virus would kill the egg and therefore stop the growth process short.

The extra complication where bird flu is involved, Professor Gust says, is that the virus cannot be grown in eggs, as is usual practice in making vaccines, because it would simply kill the eggs. Instead it has to be put through a process known as reverse genetics technology to engineer a strain that both grows in eggs and protects against the bird virus.

Even if the manufacturers were ready to go when a human-to-human virus appeared, it would still take at least six months for a vaccine to be widely available. And in that time, the virus would be likely to have made its way very quickly around the world and caused many deaths.

Whether the bird flu strain currently spreading in Asia will mutate into a form easily transmittable in humans remains to be seen. But if this particular outbreak in chickens doesn't turn into a major human pandemic some flu strain will eventually mutate into a very deadly strain and could kill millions. What we need are much faster ways to develop and produce vaccines.

One bright light on the horizon if the development of cell culture techniques for growing vaccine viruses. Chiron Corporation CEO Howard Pien claims that Chiron cell culture flu vaccine will be able to halve the production time for flu vaccine.

A: The general estimate for a vaccine product is that it takes five to six years to develop it for the market. It is entirely possible we will do this faster, but that is assuming our test is very, very positive. Currently, it takes four months to make flu vaccine in chicken eggs. We believe that time can be reduced by 50%. The net effect will be to increase output.

Chiron says they will go into Phase III clinical trials for the cell culture version of their vaccine in 2004.

Chiron expects to enter Phase III studies for its flu cell-culture vaccine this year.

The US government is trying to accelerate development of faster virus production technologies but some doubt cell culture methods will be faster.

Health and Human Services Secretary Tommy Thompson says federal officials want to urge companies to move toward newer technologies that would allow faster production of vaccine, which currently takes at least six months from egg to vaccine.

In mid-December, Thompson said he hopes some of the expected $50 million in new federal funding for flu research will be used to encourage new companies to start making vaccine using newer, egg-free technologies.

A switch to cell culture technology, which Aventis already uses to make vaccines against polio and other diseases, wouldn't speed production of flu vaccine, says Michael Decker, vice president for scientific and medical affairs at Aventis. "Let's suppose we had no chickens and no eggs. Then, cell culture is faster." But for companies with established supplies of chicken eggs, there's no advantage. "The virus takes the same time to grow in either."

The use of either cell culture grow viruses to make killed-virus vaccines is not the only imaginable approach for more rapid vaccine production. DNA vaccines could probably be produced more quickly.

Another approach is the use of DNA vaccines. Here, the gene for a pathogen protein is introduced into human cells and is then expressed to produce the protein inside the body. There are many advantages to the DNA vaccination method. For example, it is much cheaper to produce and distribute large amounts of DNA than it is to produce and distribute large amounts of protein. Also, the same strategy can be used to tackle virtually any pathogen, so multiple vaccinations are possible. Technical hurdles that need to be overcome include finding efficient ways of getting the DNA into human cells, making sure the gene is expressed once it is inside the cell, and making sure the DNA does not integrate into the genome and disrupt our own genes. There are many DNA vaccines in clinical and pre-clinical trials, including vaccines for HIV, herpes, hepatitis and influenza.

Until it becomes possible to develop and produce hundreds of millions of vaccine doses in a matter of weeks the human race is going to continue to live under the threat of a repeat of the 1918 pandemic with tens or even hundreds of millions killed. Research aimed at developing types of vaccines that can be produced more quickly ought to be a higher priority.

By Randall Parker    2004 February 02 11:47 PM   Entry Permalink | Comments (1)
2003 December 05 Friday
Future Natural Influenza Strain Mutations Seen As Great Threat

Writing in the journal Science influenza experts Richard Webby and Robert Webster see the inevitable rise of a future mutant strain of influenza that could kill millions of people.

Nature's "on-going experiments" with influenza strains "may be the greatest bio-terror threat of all", with the world alarmingly unprepared for a global epidemic, researchers warn today.

Another pandemic of the kind that killed up to 40 million people worldwide in 1918 is inevitable - and could be imminent, according to a team from St Jude Children's Research Hospital in Memphis.

Current methods for manufacturing flu vaccines take too much time.

Using current technologies, it takes as long as six months to create flu vaccines.

"The world will be in deep trouble if the impending influenza pandemic strikes this week, this month, or even this year," write international flu experts Richard Webby and Robert Webster of in Memphis.

Techniques that promise to accelerate flu vaccine manufacture ought to be tested and facilities scaled up to be ready for emergency use.

The technology exists to make a flu vaccine more accurately and much more quickly through a technique called reverse genetics, but the method is not yet approved for use in humans. The current method uses chicken eggs as a sort of incubator for viral genes, a process that involves both guesswork and time. Reverse genetics relies less on both of these factors.

"The advantages of reverse genetics is that we can do it much more quickly and have exactly what we need," Webster said, sometimes in as little as two or three weeks. Clinical trials are needed, he added.

Two families of drugs are now available for the flu, amantadine and neuraminidase inhibitors (like Tamiflu and Relenza). Existing supplies could be wiped out in days, however, Webster cautioned. "It would take about 18 months to start from primary chemicals to make more antivirals," he said.

Vaccine production facilities are not large enough to rapidly make vaccines in response to an acute emergency.

“If an influenza pandemic started tomorrow, we would not be able to head it off with vaccines because the production facilities available to produce them are grossly inadequate,” said Robert G. Webster, Ph.D., a member of the Infectious Diseases department and holder of the Rose Marie Thomas Chair at St. Jude. Webster is co-author of the Science article.

This ability to rapidly make hundreds of millions of vaccine shots is a capability that the industrialized nations ought to develop. It would be useful in an emergency in response to natural and man-made pathogen pandemics. There is also the problem of how to rapidly identify which antigens a DNA vaccine or other type of vaccine should code for. In the case of influenza outbreaks that usually can be done fairly rapidly. But for other pathogens the job can be much tougher (even taking many years) and therefore there is a need for the development of biotechnologies that could accelerate the process identifying the most promising antigens to use in a vaccine.

As for the antiviral drugs: the efficacy of existing antivirals that are used against influenza are of such limited efficacy that the FDA is criticised in some quarters for approving them for sale. When a real killer influenza pops up the ability to very rapidly develop and manufacture a vaccine will likely be of far greater benefit than the antiviral drugs. But if a killer influenza pops up what would really help the most is probably the rapid implementation of rules and the propagation of sound advice that will reduce the risk of transmission. It would help to do more research ahead of time to identify the least disruptive techniques for reducing the rate of transmission of influenza. What would be the relative value of face masks, closure of schools, avoidance touching of handrails or door knobs, and other changes to daily routines? That would be great to know.

By Randall Parker    2003 December 05 01:07 AM   Entry Permalink | Comments (1)
2003 July 06 Sunday
Has SARS Really Been Stopped?

The SARS outbreak appears to have ended. But historically influenza epidemics have always waned in the summer and for similar reasons higher temperatures may be blocking the spread of SARS.

There are also suspicions that the first outbreak in the southern Chinese province of Guangdong stopped so abruptly because of the onset of summer. The SARS virus does not survive well in a hot environment, and if most transmission is due to people touching contaminated surfaces, higher temperatures would have reduced transmission.

We aren't really going to know whether SARS has been stopped until the fall season comes to China, temperatures drop, and people spend more time in-doors. Whether we see it again also depends in part on whether there is a significant animal reservoir for it. Did it mutate in a single animal for sale in a marketplace to be able to jump into humans? Did that animal get killed and thereby end its presence in animals? Or are there many animals walking around that carry the coronavirus in a form that is infectious in humans? The answers to these questions are unknown.

By Randall Parker    2003 July 06 01:44 PM   Entry Permalink | Comments (0)
2003 June 15 Sunday
New Diseases Jumping Into Humans At Faster Rate

The Washington Post reports on the view of many infectious disease experts that the rate at which pathogens are jumping from other species into humans is increasing.

"Influenza is a zoonotic disease. HIV is a zoonotic disease. Monkeypox. SARS," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "You can go on and on."

The increasing pace is being caused by a confluence of factors that bring people into contact with a greater diversity of creatures than ever before, experts say.

Many reasons are cited for this. There are more humans. Humans are pushing into more parts of the globe. There are farming and marketing practices (e.g. the live animal markets in South China) that increase the chance of contact between humans and other species. When a disease does jump into a single human its odds of spreading into other humans is increased by faster and more widely used modern transportation. Contaminated food is spread more widely by modern transportation as well. Humans keep and trade in exotic pets.

The article mentions in passing that smallpox may have originally jumped into humans from camels. There is an interesting story behind that. Camelpox has been found to be genetically closest to human smallpox of all the known pox viruses. There is a real possibility that camelpox could mutate in a way that would allow it to jump into humans.

All the comparisons showed that camelpox and smallpox are genetically closer to each other than to any other virus. The authors speculate that the two viruses evolved from a common ancestor, possibly a rodent virus, probably after the advent of intensive agriculture about 7,000 years ago.

Gubser and Smith say the growth in the percentage of people who are "immunologically naïve" for orthopoxviruses increases the danger that these viruses will emerge or re-emerge as a threat to human health. In addition, the growth in the number of people whose immunity is suppressed by HIV infection poses a risk that the orthopoxviruses such as camelpox will jump species and adapt to humans.

There is a new theory just published about the origins of HIV. HIV may have been created by an exchange of genetic material between two Simian Immunodeficiency Viruses (SIVs).

A genetic study of SIV - the Aids-like virus that infects monkeys - suggests that HIV - the virus that causes Aids in humans - came about through the combination of two viruses in chimpanzees.

HIV may have been created by recombination of DNA from viruses that infect red-capped mangabeys and spot-nosed monkeys

In some ways, SIVcpz was found to resemble SIVrcm, a virus endemic in red-capped mangabeys.

But in other respects it closely matched another form of the virus, SIVgsn, which is found in the spot-nosed monkey.

It is possible that HIV was created by keeping primates of different species in close proximity in captivity.

"The genetics does not tell you how it arose," he said. "If you ask me to put money on it I think SIVcpz arose when monkeys and chimps were kept together in captivity. We know Asian rhesus monkeys caught SIV from African monkeys in captivity."

If this theory becomes well known and achieves some degree of acceptance one could easily imagine animal rights activists citing it as an argument against zoos.

By Randall Parker    2003 June 15 12:56 PM   Entry Permalink | Comments (1)
2003 May 06 Tuesday
SARS Death Rate And Incubation Period Estimates Raised

The latest estimates for the SARS mortality rate is even higher than the last revision upwards.

The mortality rate for those younger than 60 is between 6.8 percent and 13.2 percent, but jumps to between 43.3 percent and 55 percent for those 60 and older, the study found.

This work is being published in The Lancet.

The research, led by Dr. Roy M. Anderson and Dr. Christl A. Donnelly, both of Imperial College in London, is to be reported in Saturday's issue of The Lancet, the British-based medical journal.

The current 10 day quarantine period used for those suspected of exposure to SARS may not be long enough.

The Lancet study, based on 1,425 SARS cases in Hong Kong up to April 28, also found that the maximum incubation period -- the time it takes between getting infected and becoming ill -- may be as long as 14 days.

Here is my advice for the day: Do Not Get SARS! Also, stay the heck away from China.

By Randall Parker    2003 May 06 11:10 PM   Entry Permalink | Comments (0)
2003 May 05 Monday
China Continues To Be SARS Threat To Rest Of World

Experts fear that SARS will become endemic in China and that the need to contain SARS in China will become a long term problem for the world.

If China becomes a reservoir for Sars, other countries, particularly its neighbours, will have to maintain constant vigilance for cases arriving from the Far East.

Professor Tedder said it was possible that stringent surveillance precautions would be in place in the UK and Europe for the foreseeble future - and perhaps for years to come.

He said: "What it may prove to be is a very effective dry run - one wonders what will happen next time."

Given its mortality rate we really are lucky that SARS is not more easily transmittable. If the latest crossover of a virus from another species into humans had been an influenza with a lower mortality rate than SARS but still fairly high (say 2% like the 1918 Spanish Flu) it would not have been controlled in Western countries as easily. SARS ought to serve as a wake-up call for a future lethal virus that is more easily transmittable.

Then there is the continuing problem posed by SARS. It may become permanently established in China. If that is what is happening then it seems inevitable that sooner or later it will become established in the Indian subcontinent and Africa as well.

The World Health Organization has recently published a summary table of results of tests on how long the SARS virus can survive outside the body. The ability of the SARS virus to survive on a plastic surface at room temperature for at least 2 days provides key evidence for how SARS has been able to spread thru apartment buildings and hospitals.

Another experiment in Germany suggests that killing the SARS virus on surfaces is not a trivial matter.

German scientists found a common detergent failed to kill the virus, indicating that some efforts to sterilize contaminated areas may be ineffective. An experiment conducted in Japan concluded that the virus could live for extended periods in the cold, suggesting it could survive the winter.

On the bright side, the vast bulk of new SARS cases are happening in China and Hong Kong. But given the primitiveness of the health care system in much of China and the attempts of some probable SARS sufferers in China to avoid contact with authorities (poor Chinese people do not trust the government to care for them) it is likely that even if the Chinese government is honestly reporting all known SARS cases (by no means a certainty) there are probably cases in China that are going undetected. One should really take the WHO case numbers with a grain of salt for other reasons as well. The WHO's definition of what constititues a SARS case is narrower than the definition used by some national health authorities (notably the US CDC). India is reporting 20 SARS cases which India claims are confirmed by lab tests and yet WHO has no SARS cases listed for India. The number of SARS cases reported by WHO for the United States includes only the cases that the CDC lists as probable (and perhaps not even all of those? Or is WHO slow about updating counts?). The problem is that most people who have had a milder case of SARS do get listed as probable. Until reliable lab tests are widely used and accepted as definitive I expect WHO SARS case figures will continue to represent only a subset of all people infected by the virus.

On another brighter note, reports of relapsed SARS cases turn out to be unfounded.

HONG KONG -- A dozen former SARS patients here who were initially thought to have suffered relapses actually had other medical problems, health officials said Sunday, as the rate of new SARS cases being reported around the world slowed somewhat.

It is very unlikely that SARS will become established in Western industrial countries. Quarantines other public health measures can contain any new outbreaks that occur in large part because SARS is not too easily transmissible. However, as long as SARS is being passed around in China it threatens to make it into other less developed parts of the world.

By Randall Parker    2003 May 05 04:41 PM   Entry Permalink | Comments (1)
2003 April 29 Tuesday
People In China Evade Government Quarantine Efforts

A widespread lack of trust in their government is causing many Chinese people who suspect they are sick to avoid contact with doctors and hospitals.

"The government has said the people are panicking because they don't understand SARS, but that's wrong," said Kang, the social scientist. "They are panicking because they don't know who to rely on. The migrant workers in Beijing are afraid that if they are quarantined they won't get treated, just left there to get sick and die. Their flight is actually a rational response."

The previous report is more important than the fact that the WHO reports that SARS is declining in many of its major sites of infection.

BEIJING -As the World Health Organization announced that SARS had peaked and is declining in Hong Kong, Singapore and Canada, Chinese officials continue to withhold information crucial to combating the spread of the deadly virus, the U.N. agency's chief representative in Beijing charged Monday.

While some stock markets are rallying in reaction to WHO statements that SARS has peaked in many locations and a lot of people are breathing sighs of relief that perhaps the worst is behind us these optimistic reactions seem premature. SARS is being controlled in highly industrialized countries and also in Vietnam. But it is spreading deeper into China and there are worrying signs that it is getting a hold in India. With a 10th SARS case reported India has been reporting at least one SARS case a day for the last 4 to 5 days.

Medical experts warned that health authorities needed to do more to tackle the disease as SARS had entered the "local transmission" phase in which Indians who had returned to the country carrying the virus were now infecting fellow citizens.

If SARS becomes well established in rural India and rural China then there is no way it is going to be eradicated in the foreseeable future. There will then be a continuing risk that it will spread to still other less developed countries. An increasing portion of the world will come to be seen as made up of high risk destinations to visit. This will cut economic growth in those areas and in the world as a whole.

Individual Westerners who do not travel to regions which have SARS infection are going to continue to be at very low risk of getting the disease. In any locale where SARS shows up in the West the Western governments will conduct fairly aggressive programs to hospitalize sufferers and quarantine those who have been exposed (my guess is that other Western governments are learnng from Toronto to move quickly). The skilled personnel, supplies, and infrastructure are available to stop a local outbreak from getting out of control. Realistically a typical Westerner or resident of other industrialized countries such as Japan will be at greater risk of death from a car accident.

However, the economic impact of SARS is going to be great for the West in part because risk avoidance behaviors in the infected regions and among those who might otherwise travel to the infected regions will be so great. China is going to shut down its stock markets for at least a week. The economic effects of SARS are extending far beyond the infected countries and the global economy is slowing.

There are two big unknowns at this point:

  • Will SARS become established in poor countries outside of China?
  • How quickly and cheaply can the world economy essentially restructure itself to minimize the economic impact of SARS?

Obviously, the answer to the first question greatly affects the size of the needed economic restructuring. But there are already many signs that computer and communications technologies are being used to reduce the economic impact of SARS. For instance, home banking use is surging in Hong Kong. Also, Video conferencing is enjoying a boom. Teleconferencing, telecommuting, email, mail order shopping, and other means of reducing one's exposure to other people are all helping to reduce the impact of SARS on the world economy.

On the bright side SARS is very mild in children and children who have SARS appear to be much less infectious than adults.

The researchers discovered the two distinct patterns of disease. The five teenage patients had symptoms similar to SARS in adults - muscle pains, malaise, chill and rigour. However, the younger children had mainly coughs and runny noses with no muscle pains or chills.

Update: A measure of the economic impact of SARS on Beijing.

And there is another more ironic proof of the seriousness of the situation — It is dusk here right now, and it is a clear, blue, glorious evening. The quality of this sky you do not see except when someone is in town that the government wants to impress, such as the International Olympic Committee, and the government shuts down the main thoroughfares and any industry that is going to pollute.

By Randall Parker    2003 April 29 02:23 PM   Entry Permalink | Comments (1)
2003 April 28 Monday
Aircraft Air Is Low Risk As Source Of SARS

Air flights are not a huge source of risk for SARS infections. Aircraft use high-efficiency particulate air (HEPA) filters and take all bacteria and viruses out of the air at a very fast rate. Airplanes have better air filtering than commercial buildings.

Plane air is completely replaced with air from outside the aircraft 20 to 30 times every hour. This compares favourably against one to three times an hour in a typical building and five to seven times in a hospital operating theatre.

Granted, one could be seated on an aircraft right next to someone who has Severe Acute Respiratory Syndrome (SARS) and that person could cough on you. But consider the odds. The vast majority of those who have SARS are on the ground at any given time. Most do not fly from one place to another before being diagnosed and hospitalized. Few SARS cases to date have been traced back to exposures that happened on aircraft.

The biggest single kind of location for passing SARS on has been in hospitals. But most hospitals do not have SARS cases and so hospitals outside of areas which have a high level of SARS cases do not pose a risk as a source of SARS infections either.

The biggest danger from air flight comes from flying to a place that has a lot of SARS cases. Well, anyone who is worried about catching SARS should avoid visiting those (primarily East Asian) locations. The biggest danger to the rest of the world for SARS comes from the fact that people can fly from SARS-infected areas while still at early undiagnosed stages of infection. The greater danger from infected air passengers comes from the possibility that they will pass SARS along while staying for days at their destinations.

By Randall Parker    2003 April 28 10:19 PM   Entry Permalink | Comments (0)
2003 April 26 Saturday
SARS Looks Set To Spread To Less Developed Countries

Public health experts are becoming increasingly pessimistic about the prospects for stopping the spread of SARS.

With infections now confirmed in two-thirds of China's provinces and mounting daily, ''hope dwindles'' for wiping out the disease, WHO virologist Wolfgang Preiser said from Shanghai. Even in ''Singapore and Hong Kong, very rich places, they still have problems. We are worried about the spread to poor provinces, maybe countries such as India and Bangladesh,'' where ''we don't think they have the capacity to stem the tide once it's introduced.''

''It may have happened already,'' he said.

Within the past day 3 new cases of SARS have been identified in India.

The Health Ministry has confirmed three more cases of SARS in India, which takes the total number in the country to seven. Of the three freshly confirmed cases, one is being treated in Kasturba Hospital, Mumbai, the second in Apollo Hospital, Kolkata and the third in Naidu Hospital, Pune.

If it was my decision to make I'd order the cessation of all commercial passenger flights between East Asia and the countries of the Indian subcontinent and Africa. Those countries do not have the capacity to contain SARS. They are too poor and most of their populations have little or no access to modern health care facilities.

Poor countries in the Indian subcontinent such India are unwilling to take sufficiently drastic steps to stop SARS in advance of a major SARS outbreak in their region. This is foolish. They lack the infrastructure needed to control SARS. As a result, the industrialized countries will have to adopt very rigorous measures at borders and ports of entry to detect SARS carriers because SARS is going to become endemic in much of the world. Thermal imaging and testing for SARS in all arriving and departing passengers will have to become routine at all ports of entry.

Reliable, accurate, and cheap DNA-based Real-Time Polymerase Chain Reaction (RT-PCR) SARS tests are the greatest hope the industrialized countries have for controlling SARS in a way that minimizes the economic impact. An ideal test would be able to use sputum so that a nurse would not be needed to draw blood. To allow testing of large volumes of business travellers an ideal testing device would need to be automated and have a high thru-put rate.

If all SARS carriers could be identified among international travellers even before they boarded aircraft to fly to a SARS-free country then regular business and holiday travel between SARS-free countries could proceed as normal. Also, anyone willing to risk going to an area where SARS is present would not need to be quarantined on return. Patterns of business meetings could be shifted to allow people from SARS-infected areas to travel to SARS-free areas to facilitate customer-supplier meetings. Then people in low risk areas would not have to travel to high risk areas to do business with the high risk areas.

If Taiwan could develop large-scale DNA-based SARS testing systems and use them to make Taiwan SARS-free then Taiwan could gain an advantage by making Taiwan as a place where mainland Chinese businessmen could travel to meet with businessmen from other parts of the world to do deals. Everyone coming to Taiwan could be tested before and on arrival for SARS virus. That way SARS carriers could be kept out. Business could be done in a safe environment fairly close to China. This would reduce the economic disruption that SARS is causing.

There are countries that are willing to take drastic steps. For instance, in order to keep out new cases of SARS Vietnam may close the 800-mile border it has with China.

Vietnam's northern Quang Ninh province, home of the Halong Bay tourist attraction, began barring Chinese tourists at its land border gates and waterways. Hanoi's health ministry has recommended the country seal all its borders with China indefinitely.

Countries that lack the capacity to fight SARS should be willing to close their borders to visitors from countries which have SARS cases.

The New York Times has an excellent long article that traces the spread of SARS. While China made huge mistakes in its handling of the crisis Singapore shines as a textbook example of how to aggressively quarantine and isolate potential SARS carriers.

But even in a small country, placing thousands on quarantine has been a strain. Last Monday, after a case of SARS was discovered in a vendor at Singapore's largest vegetable market, the Ministry of Health ordered all 2,400 food sellers to report for quarantine, up from a total of 467 quarantined before. Since 80 percent of the country's vegetables pass through the Pasir Panjang Market, restaurants were bracing for a shortage of greens.

Hong Kong has done a much worse job than Singapore in protecting health care workers.

In Singapore, with its aggressive system of identifying and isolating SARS patients, no health care worker has been infected for over three weeks. But in Hong Kong, 2 to 10 doctors and nurses are falling ill each day, in part, health officials there say, because doctors are still not identifying them as SARS victims early enough and are admitting them to ordinary wards.

Canada has also been too slow to do quarantines and to adopt extreme measures to protect health care workers.

Only recently -- weeks, if not months, after SARS hit -- have officials in China and Canada begun cordoning off entire buildings containing infected patients. Physicians such as Abraham Verghese say that slow response permitted the deadly virus to infect many others in their own countries and beyond. "The lesson of Hong Kong, China and, to some degree, Singapore is if you don't aggressively isolate, this thing can get out of hand," said Verghese, director of the Center for Medical Humanities and Ethics at the University of Texas Health Sciences Center at San Antonio.

The long incubation period helps SARS to spread around the world.

Its apparent incubation period of two to 10 days is long enough for infected people who are asymptomatic to travel "from one city in the world to any other city having an international airport".

SARS is most likely a coronavirus. Other known coronaviruses can survive on surfaces for 24 to 48 hours.

Research done decades ago showed that the type of coronaviruses that cause many colds can remain viable on surfaces for 24 to 48 hours, depending on air temperature and humidity.

The US CDC reports that there is a preliminary study done in Hong Kong that shows SARS can survive on an exposed surface for at least 24 hours.

How long do coronaviruses survive in the environment?
In general, enveloped viruses such as coronaviruses do not last a long time in the environment. In earlier studies, a different coronavirus was shown to survive for up to 3 hours on surfaces. At this time, it is uncertain how long the newly discovered coronavirus associated with SARS can survive in the environment. In one preliminary study, researchers in Hong Kong found that both dried and liquid samples of the new coronavirus survived as long as 24 hours in the environment. Additional studies are under way to examine this important question.

People who live in areas where SARS is present should wash their hands frequently, avoid touching their faces or other parts of their bodies with their hands, and minimize the number of surfaces they touch in public areas. There are lots of ways to reduce one's need to touch surfaces. Do not use hand rails. Keep your hands on your lap when sitting in a public place. Use a stick or other object to press elevator buttons. Become more aware of where you are going and what you will have to touch in order to get there.

Update: If SARS does make it to the less developed countries the number of peope killed could be enormous.

With many cases still unresolved, a better current estimate of the deadliness of SARS may be the number of deaths as a proportion of resolved cases. Those numbers for Hong Kong, Canada and Singapore are 15.8, 18.3 and 13.7 per cent. But these too could be misleading if, for example, it takes longer to recover from a disease than to die from it.

There are other indications that the SARS death rate may be higher than expected. Mortality among infected SARS patients might end up being in the range of 8% to 15% of infected patients. Keep in mind that the death rate varies as a function of age and the death rate is higher in the elderly. Still, overall it is lookiing like the death rate from SARS is going to turn out to be at least 10%.

"If one looks carefully at the WHO figures on mortality and recovery rates, it is running, unfortunately, at 10 per cent," Professor Roy Anderson of Imperial College said.

Update II: Chinese infectious disease experts see a coming third bigger wave of SARS infections in China.

Bi and other experts have said that Beijing officials did not take adequate measures last week to stop Beijing's huge migrant labor population from returning home, and thereby possibly spreading the disease across China.

"The government held meetings for hours with no decision and meanwhile, everybody left town," Bi said. "Beijing is the second peak of the disease. The third one, in the countryside, will be much, much higher."

My fear about the coming third wave is that it will spread SARS into areas adjacent to China. Granted, most land borders of China are in pretty sparsely populated and harsh environments. But SARS could spread across Central Asia and eventually into more densely populated Asian countries.

Update III: Two more cases of SARS reported in Calcutta and Bombay.

Two more cases of Severe Acute Respiratory Syndrome (Sars) have been reported in India, taking the total number of people infected with the pneumonia-like virus there to nine.

SARS cases seem to be popping up in India daily. This is not good. All it would take is for one of these cases to be a "super-infecter" (also called "super-carriers", "super-spreaders" or "hyper-infecters" in some reports) for the disease to start spreading rapidly there.

Keep in mind that SARS cases in India are orders of magnitude more significant than SARS cases in more developed countries because India is far less able to control the spread of a disease. Places like Canada, the United States, Taiwan, and Singapore have the ability to identify cases, isolate them, trace those who might have been exposed, and generally take the steps that will eventually put a halt to the chain of spread. But if SARS makes it into areas where there are large numbers of poor people and primitive health care the disease will become a greater threat to the entire world. Pay especial attention to reports of SARS cases in the Indian subcontinent and Africa. The battle to prevent a global SARS pandemic will be won or lost in the poorest countries.

By Randall Parker    2003 April 26 03:41 PM   Entry Permalink | Comments (0)
2003 April 25 Friday
1 Million People Have Fled Beijing Out Of SARS Fears

Growing fear of Severe Acute Respiratory Syndrome (SARS - also called atypical pneumonia in the Chinese media) has caused 1 million people to flee Beijing for other parts of China.

There was a continued exodus from Beijing today as thousands of people attempted to flee the epidemic and return to their home towns all over China. At the Beijing airport, travelers wearing face masks boarded planes out of the city. Local journalists estimated that almost 1 million people, about 10 percent of the population, had already left the capital.

This is an astounding figure. When is the last time that so many people took such drastic action in such a short period of time in response to a natural biological threat? Imagine how people would respond today to an even bigger infection threat. SARS does not spread as easily as influenza. Some day a new influenza strain that is more lethal than the typical influenza strains will arise. It could cause panic around the world.

The rush to flee Beijing has been fueled by the fear that the government would declare martial law and close off the city from the rest of China. The government has had to announce that it would not impose martial law but it is unlikely that the Beijing public believes it.

This is guaranteed to spread SARS further and faster. Infected people riding on airplanes, trains, and buses will pass the disease along to other passengers. They will also pass it on to people they have contact with at their destinations.

The treatment of those suspected of being exposed to SARS in Beijing is considered to be so harsh that people may be hiding their SARS symptoms from the authorities.

Sars suspects are being victimised in Beijing, where thousands have now been put in compulsory quarantine, a World Health Organisation specialist, Dr Wolfgang Preiser, said yesterday.

"If you make it hell for them, they go into hiding," Dr Preiser, a German virologist, told reporters in Shanghai.

While some might cheer the prospects of the Chinese government coming under intense criticism from its own population for the government's handling of SARS keep in mind that a revolution in China would by itself kill millions and that the chaos of a revolution would cause SARS to spread even faster.

People are stockpiling food.

Supermarkets reported a roaring trade in staples such as rice and cooking oil as rumors swirled the city would be isolated, while many other shops simply closed up as scared residents stayed at home.

At least this is a rational response. To reduce the risk of exposure in a high infection area it makes sense to buy a lot of food at a time and shop less often. It also makes sense to shop during the off-hours to reduce the number of people one is exposed to. If there was a big outbreak it would make sense to have open air markets so that the air would be dispersed quickly.

By Randall Parker    2003 April 25 08:45 PM   Entry Permalink | Comments (0)
2003 April 24 Thursday
What Should Be Done About SARS

There is lots of bad news about Severe Acute Respiratory Syndrome (SARS). SARS is continuing to spread and to establish itself in more locales. The death rate has risen. It appears to mutate rapidly. There appears to be a more lethal strain that also infects the intestines and SARS is causing kidney failure in some patients. Tens of thousands of people (if not more) are fleeing Beijing and in the process helping to accelerate the spread of SARS to more parts of China. Effective drug therapies and vaccines are both distant prospects.

SARS Is Mutating Rapidly

Different SARS coronavirus isolates have been sequenced and compared and many DNA sequence differences have been found.

The mutations were seen in all five of the viruses' known functional genes, with most of them occurring in the gene that carries the instructions for the distinctive spikes that jut from the outside of the virus, according to Siqi Liu, associate director at the Beijing Genomics Institute, part of the Chinese Academy of Sciences.

Those mutations on the outer coating are important because they can create new strains of the virus that are immunologically distinct. A person who has already been infected by SARS and recovered from it would be at risk of reinfection if exposed to a different strain of SARS that had undergone a lot of mutations in genes that code for outer layer proteins. Also, rapid mutation that generates immunologically different strains makes the job of development of vaccines more difficult and makes the period of protection from a vaccine version shorter.

Coronavirus mutation has been a problem in the development and use of vaccines in the poultry industry.

"The ability of the virus to mutate has been a real problem in poultry vaccines. "The virus has the ability to change quite quickly - a vaccine might be suitable for a while, but not forever."

As I've previously posted, vaccine development time for SARS is measured in years. Well, this news that SARS is mutating rapidly will most likely lengthen the amount of time it will take to develop a vaccine. This is not good.

Higher SARS Death Rates In Hong Kong

Rapid mutation can lead to more virulent strains. A more deadly SARS strain that attacks the intestinal tract may have already arisen.

The Amoy Gardens patients are three times as likely to suffer early diarrhoea, twice as likely to need intensive care and less likely to respond to a cocktail of anti-viral drugs and steroids. Even medical staff who caught the infection from Amoy Gardens patients are more seriously ill, Yuen said.

SARS is attacking the kidneys in some patients

Tom Buckley, the head of the intensive care unit at Hong Kong's Princess Margaret Hospital, said organ failure was also now becoming more common.

"Initially patients were presenting with just respiratory failure," Dr Buckley said. "Now we're seeing renal failure and other organ failure."

The death rate for older folks is high.

Statistics in Hong Kong show that the death rate among people younger than 55 is 3.6 percent. For patients between 65 and 75, it is 18.9 percent. For those older than 75, the death rate is 28.6 percent.

The death rate from SARS in Hong Kong has increased to 7.2 per cent of reported cases - up from about 5 per cent earlier in the crisis - and officials fear it may go higher.

There are a number of possible reasons why the death rate is increasing. It could be that many of the initially infected tended to be healthy business travellers and health care workers. Now SARS is spreading from them to their families including older folks who are more at risk of dying from infections. Or the virus could be becoming more deadly as it mutates. Or some people may have been sick for weeks before finally succumbing. The real explanation may turn out to be a combination of factors.

Fear And Panic In Beijing

The schools are closing in Beijing China.

CHINA: Beijing closed schools for two weeks and sent 1.7 million pupils home yesterday as the country struggled to contain a Sars outbreak thought to have originated in its south.

A major Beijing hospital has been quarantined.

The 1,200 bed Beijing University People's Hospital was sealed off because of SARS today and police were posted to stop people going in or out, hospital staff said.

People are fleeing Beijing by the thousands.

BEIJING, April 23 -- Thousands of people mobbed Beijing's West railroad terminal today in desperate attempts to flee the city as the capital reported another triple-digit increase in the numbers of people infected with SARS and nine more deaths.

Flight of people from infected areas is helping to spread SARS further.

But the relative safety of many of the provinces could prove shortlived if the infection is spread by the railway system.

If the infection is spread by the railway system? Why wouldn't it be spread that way? The infection is already being spread to many provinces of China. Surely some of that spread is happening via rail travel. But cars, airplanes, and other means of transportation are surely contributing as well.

When people start trying to get rail tickets for any place they can get a ticket for then real panic has set in.

Laden with burlap bags and potato sacks, they boarded trains for whichever destination they could get a ticket as the death toll jumped by 25 per cent in the Chinese capital.

Think about it. People are fleeing in panic from the capital of the world's most populated country. Most of the country has health care facilities that are primitive compared to Beijing's. People are spreading out to those more primitive places. My guess is that SARS will achieve pandemic status in China. The Chinese government's honesty (or lack thereof) in reporting SARS cases is becoming irrelevant as SARS spreads into the poorest areas of China. We will not know how many people in China have SARS because most of the future Chinese sufferers will be in areas too primitive for them to be seen by qualified medical professionals.

At least the people fleeing Beijing are trying to avoid enclosed areas where the risk of breathing airborne virus particles is greater.

A sea of faces in white cotton masks scanned coveted train tickets, waiting for hours outside in the chilly air rather than linger in crowded, enclosed waiting rooms.

The World Health Organization Extends Its Travel Advisory

The WHO says do not travel to Beijing or Toronto.

BEIJING/TORONTO (Reuters) - Saying SARS was still spreading out of control, the World Health Organization tightened travel advisories on Wednesday, adding Beijing and Toronto to the list, while authorities in Beijing started quarantines.

Canadian authorities are upset by this advice.

Canada has responded angrily after the World Heath Organization (WHO) listed Toronto with Beijing and China's Shanxi province as places travellers should avoid because of the danger of Sars.

The Canadian government is being parochial. Steps to stop the spread of SARS need to be taken before it becomes an even bigger threat. The WHO should have gone much farther and told people to avoid China entirely. Plus, it should have asked that people in infected areas not travel from those areas.

What The Industrialized Countries Should Do

China's government waited too long before acting. The spread of SARS to the poorer provinces of China makes it unlikely that the Chinese government will succeed now in stomping out SARS entirely. That, in turn, increases the odds that SARS will spread from China to even less developed countries. If SARS becomes established in India or, even worse, in Africa then it seems likely to achieve pandemic status.

The problem is that the more places SARS becomes established the greater the chance that on any given day there will be someone bringing SARS into areas where it hasn't become established. Plus, the greater the panic becomes the more people will flee infected areas and infected countries and carry SARS with them in the process.

The economic costs of trying to prevent the spread of SARS need to be weighed against the economic costs of what happens when it becomes established. In countries where SARS has taken root the economic costs of people becoming afraid to travel, go to jobs, meetings, and to go shopping in markets is becoming enormous. The Western industrialized countries need to work hard to prevent SARS from becoming big enough to start changing the behavior of a substantial portion of the population of each country. The economic costs would become staggering if SARS did come to be viewed as a threat to the population of the Western nations.

Countries should reduce the issuance of visas for people from infected areas. Some countries already are doing so. Saudi Arabia has stopped issuing visas to visitors from several East Asian countries. So has Israel. Belize has banned visitors from several countries including Canada. Singapore, Hong Kong, Tokyo-Narita, Beijing and other cities with international airports are installing thermal imaging systems to scan passengers for fevers. These are certainly steps in the right direction. More international airports should institute thermal imaging screening and other methods of screening incoming passengers. Unfortunately, it is the countries that are least able to afford to handle a SARS outbreak that will also be least able to afford extensive screening measures at their international airports.

Fast DNA-based SARS tests are essential for stopping the spread of SARS. As soon as fast DNA-based SARS tests become reliable the industrialized countries should use the tests extensively. At the very minimum, all suspected SARS cases and all their contacts should be tested and tested again. However, even more extensive testing regimes could be imagined. For instance, all people coming from infected areas could be tested or, for even more protection, all people coming into a country from any origin could be tested.

Infected areas that are relatively affluent and capable of carrying out fairly sophisticated measures to control SARS ought to consider testing their entire populations. For instance, Singapore's economic losses from SARS are so large and the benefits of being SARS-free are so large that once cheap and fast SARS tests become available city-state of Singapore ought to consider testing its entire population. Also, if a DNA-based test is not reliable within the first day or two of infection Singapore could consider putting people into quarantine for a day or two upon entrance into Singapore in order to test them again before letting them out into their general population. One way to make such a system workable would be to set aside hotels to use for quarantine and then to make each hotel receive only people who arrive on the same day with a rotating list of hotels looping thru the quarantine cycle.

The Eurasian land mass faces a more difficult task to contain SARS than do places that are geographically isolated with smaller populations. Countries like Taiwan, Australia, or New Zealand ought to be able to totally stamp out SARS and keep it out once fast DNA tests are available. But if SARS becomes established in Central Asia it will be able to jump across borders of impoverished countries and maintain its presence far more easily.

If SARS becomes established in countries that are significant sources of illegal immigrants then attempts to control SARS spread at borders of industrialized countries will become considerably more difficult. A SARS epidemic in Mexico would make SARS control in the United States much more difficult while a SARS epidemic in the Middle East or Africa would pose similar problems for Europe.

See the SARS web sites of the World Health Organization and the US CDC for their latest information.

Update: The more industrialized countries ought to start taking more drastic measures now to help the poorer countries detect SARS sufferers entering their countries. For instance, an effort by the United States to help Mexico and Central American and Caribbean countries to screen international visitors for SARS infection (e.g. by training airport workers, providing thermal imaging machines, and eventually supplying help in testing passengers) will help the to prevent the spread of SARS into the United States. Either that or the United States had better be prepared to deploy troops on a massive scale to keep out illegal aliens coming up from Mexico potentially carrying SARS. That troop deployment may become necessary anyhow. SARS could be spreading in Mexico right now without our even being aware of it.

If the Asian Times staff are right China is already doing triage to decide in what parts of its country it will try the hardest to control SARS. The Chinese government may have already resigned itself to the wide spread of SARS into poor interior provinces and may be focusing its attention on Shanghai and other key trading and commerce cities. The industrialized countries need to start planning how they are going to keep a world SARS pandemic from reaching into their populations and disrupting the industrialized economies.

Update II: Time Magazine has an excellent article that confirms the widely suspected continued cover-up of SARS cases in Shanghai.

A doctor at the Shanghai Contagious Diseases Hospital told TIME that there are more than 30 suspected cases have been admitted to their hospital's facilities, nearly double the official suspected caseload for the whole city.

Basically, local authorities in China still are hiding the truth about SARS. Plus, in the poorer sections of China where SARS is spreading the local authorities will not even have the ability to know for themselves how many SARS sufferers there are. It sure looks like SARS is going to continue to spread thru China and therefore its chances of spreading to other parts of the world are probably increasing. The industrialized countries need to start scaling up to try to halt the spread of SARS into regions ill-equipped to handle it.

Once cheap fast SARS tests become available one great way to slow the spread of SARS would be to require the testing of all passengers on flights everywhere in the world. Also, all people crossing borders by other means should be tested as well.

Update III: The SARS death rate is now thought to be between 8% and 15%.

The research by Professor Roy Anderson, due to be published in a medical journal next week, is expected to say the virus could kill between 8% and 15% - or one in seven - of those infected.

Keep in mind that SARS has a much higher death rate in the elderly. If you are young your own odds of dying from SAR woul be lower than this latest estimate and if you are old your odds would be much higher.

By Randall Parker    2003 April 24 04:09 AM   Entry Permalink | Comments (2)
2003 April 18 Friday
Fear Of SARS Makes Beijing Appear Deserted

The fear of Severe Acute Respiratory Syndrome is causing an increasingly panicked response in Beijing China.

At Bank of China branches, there were no lines. The traffic at Western Station, the city's main rail terminal, has dropped 75 percent, to 80,000 passengers a day.

Beijing universities are closing.

More than half of universities in Beijing said they would close indefinitely as the highly infectious disease spreads there.

It is important to remember that the coronavirus that is the probable cause of SARS is nowhere near as easily spread as influenza. Yet, as previous history demonstrates (most notably the 1918 Spanish Flu), very deadly influenza strains can infect the human population. Given that SARS can cause this degree of fear and panic and economic disruption then just imagine the effects on human behavior of an especially deadly influenza epidemic. Countries would close their borders. Cities around the world would become ghost towns. Natural biological phenomena still have the capacity to cause huge changes in the behavior of literally billions of people.

What I'd like to see come out of the SARS epidemic is a wider appreciation of the need to develop better capabilities to respond to natural disease outbreaks in the human population. Much of what needs to be done to prepare for natural disease outbreaks is also is helpful for handling bioterrorism attacks. Better monitoring systems are needed for both natural and man-made disease outbreak scenarios. Faster methods of identification and isolation and characterization of pathogens and faster methods for developing and manufacturing vaccines are all helpful for both types of scenarios. Advances in biotechnology are needed to speed up all the steps of response to a new disease.

Another area that needs to be looked at is how to allow people to carry out more of the normal activities of business and commerce with less exposure to other humans. What simple cheap things can be developed to allow people to move around and do things without coming into as much contact with surfaces other humans have touched or air that other humans have coughed particles into.

I can imagine all sorts of simple and cheap ways to reduce exposures. For instance, how about short sticks to use to press elevator buttons? Or how about more foot operated devices such as restroom soap squirters and water faucet operators so that people don't have to touch surfaces that other people touched?

Another important area that needs work is the development of better facial masks. This is an area that cries out for nanotechnological developments to create material that will filter air more efficiently and last longer. Masks should not become less efficient as they build up moisture from a person's exhalations of breath. Masks should be able to take more particles out of the air with less resistance so that breathing with them is easier.

By Randall Parker    2003 April 18 01:29 PM   Entry Permalink | Comments (3)
2003 April 17 Thursday
Singapore, Hong Kong Use Thermal Imaging To Detect SARS

Singapore is installing thermal imagers to detect elevated body temperatures in arriving passengers.

Airline passengers arriving in Singapore from certain Sars-stricken areas are now being scanned for the disease by a military-grade thermal imaging camera, which will detect any increase in temperature, officials said.

8 units are being installed in Changi airport.

One of the units is currently in use and another eight will be installed by the end of the week, Ong told The Associated Press.

People with hot skin will be looked at more closely by health officials.

Those who show up on the camera screen as “hot bodies,” or with a temperature greater than 37.5 C (99.5 F), will be pulled aside to have their temperature taken by a nurse, said government spokeswoman Evelyn Ong.

Singapore will also deploy thermal imagers to its border checkpoints with Malayasia. Other countries are following Singapore's lead as has been the case throughout the SARS crisis. Hong Kong's airport is also being equipped with thermal imaging to scan passengers.

In Singapore and Hong Kong, airports are being equipped with thermal imaging systems that can pinpoint feverish passengers

Thermal imaging is just one of the technologies being deployed in novel ways to fight the spread of SARS. The Ontario Province of Canada may join Singapore in placing electronic tracking bracelets on people exposed to SARS in order to monitor compliance with quarantine restrictions.

Dr. Young acknowledged the province is giving some consideration to putting electronic bracelets on people reluctant to stay in quarantine, as has been done in Singapore. "We're thinking about that and looking at that," he said. "There may be some legal issues involved."

Thermal imaging and electronic quarantine enforcement are just two of the ways that modern technology is changing how disease outbreaks are fought. The potentially most powerful tool in the modern epidemic fighting arsenal is DNA detection technology placed on DNA chips using low cost mass production. There are promising signs on that front.

Artus Biotech has announced a 2 hour SARS detection assay that detects SARS coronavirus DNA.

Based on the discovered genetic sequence, the BNI has established a real-time PCR (Polymerase Chain Reaction) diagnostic test from which results can be obtained within two hours. From that test, artus developed a ready-to-use system (RealArtTM HPA-Coronavirus RT PCR Reagents) produced under GMP conditions (Good Manufacturing Practice). It will be available from artus and its subsidiaries in the USA and Malaysia from Monday, April 14th, on. Thomas Laue, project manager at artus says: "By providing this assay quickly, we hope to contribute to the standardization of SARS diagnostic worldwide. The early and rapid detection of the virus will be our small share in controlling this epidemic plague." The PCR assay directly detects parts of the new Corona virus in throat swabs, sputum and faecal samples. The RealArtTM HPA-Coronavirus RT PCR Reagents assay delivers results very quickly. The real-time PCR technique improves specificity, allows interpretation of results during the test and provides data about the quantity of the viruses in the sample material. Classical tests like antibody assays in blood allow detection of an infection normally much later, i.e. ten to twenty days after infection. The prompt results of the RealArtTM HPA-Coronavirus RT PCR Reagents assay allows immediate countermeasures by fast diagnosis, e.g. of travellers. By this, the rapid spread of the disease can be prevented.

Hot on the heels of the Artus announcement Singapore's Genome Institute has announced a 3 hour SARS coronavirus detection assay.

The state-run Genome Institute of Singapore said its new test would take three hours and may be sensitive enough to detect the virus in its early stages before a person develops Sars symptoms such as high fever and a dry cough.

How might the SARS outbreak be ended? Picture cheap, fast, and easy-to-use SARS virus detection tests that can detect SARS at a very early stage of infection. Such a test could be employed far more widely than quarantines. Everyone flying from an area where SARS has spread could be tested either before they get on the airplane or shortly after arrival at their destination airport and not released until their test shows a negative result. The same practice could be used at high risk ground border crossings as well. Plus, anyone found by either conventional thermometers or thermal imaging to be running a temperature could be tested and held until the result of the test is known.

If SARS testing could be made incredibly cheap then a more radical approach will become possible: test everyone for SARS. One could just test everyone in countries where SARS is spreading. Or one could, in the extreme, test the whole planet's population. If the testing was done in a relatively short period of time in a geographic area before non-tested people could pass along the virus to tested people then the disease could be eradicated from the human population in the area tested. Then in that area all people who entered could be tested.

Massive testing as a method to control the spread of a disease is easier to do for areas that are geographically isolated. For instance, it would be far easier to do this for Australia or Hawaii than it would be for a country on the Eurasian landmass. It would also be easier to do for areas that, for whatever reason, have little in the way of cross-border traffic.

The speed, cost, and ease of use of a test are not the only elements needed to make massive testing a feasible way to stop a dangerous disease outbreak. Another crucial element is the speed with which the test can be developed in the first place. SARS does not spread as rapidly as influenza and so it has not reached epidemic status in many locations. But the approximately 2 months that it has taken to develop fast tests for SARS (China knew about SARS 5 months ago but kept it secret and so the Western scientists have had only 2 months to identify the cause of the disease and to make tests for it) would be too long of a time for, say, a new and highly deadly influenza strain. However, it seems reasonable to expect that advances in nanopore technology, microfluidics, and other areas of biotechnology and nanotechnology will gradually shrink the amount of time it takes to identify a new pathogen and to sequence it. Once it is sequenced the creation of a new test for it can be done very rapidly.

What we are seeing in the response to the SARS outbreak is the development of elements of the future high tech public health disease fighting arsenal. Automated systems to detect disease and track human movement will only become cheaper and more powerful. Also, many other areas of relevant technology will surely see improvement. The current generation of facial masks will almost certainly be supplanted by greatly improved materials manufactured using nanotechology. The ability to protect a person from exposure will advance in a large variety of other ways including more advanced air filtration systems (again designed using nanotechnology), fancy personal instruments for monitoring individual health, and detection systems for airborne pathogens located in crowded public places. We may some day witness public health officials dispatched rather like police and emergency workers to quarantine an area and its occupants because a detector in some restaurant, airport, or hotel has signalled the presence of a dangerous pathogen.

Ultimately, just as technological advances have accelerated the rate at which diseases can spread other technological advances promise to entirely stop future epidemics at their very start. We may some day live in a future in which natural disease pandemics no longer happen.

You can read more about SARS from a more biological and public health perspective in my FuturePundit Natural Dangers Archive. For economic impacts see the ParaPundit Political Economics Archive. For what the response to SARS says about open versus closed societies see the ParaPundit Open Versus Closed Societies Archive.

By Randall Parker    2003 April 17 10:53 AM   Entry Permalink | Comments (3)
2003 April 14 Monday
China Leaders Finally Acknowledge Seriousness Of SARS

As the number of SARS cases in China continues to increase and as SARS shows up in additional parts of China the Chinese leadership has begun to publically acknowledge the seriousness the problem.

Chinese President Hu Jintao admits to being worried about SARS.

"Since the discovery of the SARS cases, I feel very worried. I feel anxious for the masses," Chinese President Hu Jintao said today.

The message from President Hu was broadcast using his own voice to underline the point.

It was his first public comment on SARS and, in an unusual step, the national evening news broadcast his own voice instead of having an announcer read his comments.

Chinese Premier Wen Jiabao says the situation remains grave.

``Much progress has been made in combating the disease, with the epidemic brought under control in some areas, but the overall situation remains grave,'' Mr Wen was quoted as telling a national conference.

These statements are being reported by the Xinhua News Agency and major Chinese newspapers. The Chinese population is still being told that the spread of SARS is being controlled. The official message is still that the government has a handle on the situation. But the problem has gotten large enough and so visible internationally that the Chinese leaders have had to come closer to admitting to their own people the full extent of the problem. It is likely that SARS cases known in Chinese hospitals are still going unreported to the World Health Organization. But it is becoming too hard to cover it up.

Previous official statements that China had SARS under control were scaring away foreign visitors who didn't trust the excessively optimistic picture the Chinese authorities were painting.

Foreign diplomats said the main reason for China's slightly more transparent line on Sars appeared to be a realisation that the previous blithe assurances were scaring more potential foreign visitors than they were reassuring. Mr Wen was now trying a different tack to limit damage to the country's economy.

The official acknowledgement of the scope of the problem may signal that the Chinese authorities are going to try harder to fight the spread of the disease. These comments from top leaders were accompanied by the announcement that China will begin screening rail and aircraft passengers for symptoms of SARS and quarantine suspected SARS cases.

The problem is that China has already lost its best opportunity to control the SARS epidemic before it reached pandemic status. China's best chance was to contain SARS where it started at an early stage. One obvious reason to try to stop a disease at its earliest stage of spread is that the smaller an area it exists in and the fewer infected by it the easier it will be to contain it. But the other less obvious reason is that SARS originated in the Chinese province best equipped medically to contain an epidemic.

Due to its proximity to Hong Kong the Guangdong province of China, the origin of the initial SARS infections, has industrialized much more rapidly than the rest of China. Therefore Guangdong is more affluent and this greater affluence has translated into greater wealth flowing into health care facilities in the province with more hospitals equipped with modern medical equipment, test labs, and drugs. The wealthier hospitals and clinics of Guangdong province have a greater capacity to handle SARS than is the case for the rest of China. Public health experts are quite aware of this situation. In their preliminary report of April 9, 2003 the World Health Organization team in China made note that as SARS spreads from Guangdong into the rest of China it is spreading into areas far less able to handle the disease.

However, the team found an urgent need to improve surveillance in the countryside to head off new outbreaks in rural areas. The team was further concerned by an increase in sporadic cases, which could not be linked to a particular transmission chain, as such cases raised questions about the adequacy of contact tracing. In addition, the report noted many remaining concerns about the ability of other provinces, where health systems are not as strong as the one in Guangdong, to respond promptly and effectively to the challenge of SARS. In Beijing, for example, only a minority of hospitals make daily reports of SARS cases. Contact tracing is another problem in Beijing and does not appear to be carried out systematically. Failure to perform careful contact tracing will allow the disease to spread. The team observed that many of China’s poorer provinces may not have adequate resources, facilities, and equipment to cope with outbreaks of SARS, and underscored that Guangdong’s capacity was exceptional among China’s provinces. In Guangdong, the SARS outbreak placed an enormous strain on the health care system. The Guangdong Infectious Disease Hospital (Guangzhou No. 8 People’s Hospital) had 150 of its 400 beds occupied by SARS patients daily during the second week of February. The team noted that the response of the health care system has been exemplary, and commended the dedication and bravery of doctors, nurses, and others working in clinics and hospitals.

Even wealthier Guangdong's handling of SARS is far from perfect. Poor people infected with SARS are being turned away from Guangdong area hospitals.

The man, who was also exhibiting symptoms of SARS, owed the hospital $250, said Chen's daughter, Chen Lili, who was visiting her father at the time. "They made him pack up and go," she said. "Who knows what happened to him? He had no money and he was sick."

These patients are sent home where they can spread the disease to family members and thereby continue the spread of SARS.

The WHO is worried that SARS may be spreading thru other provinces.

"We're very concerned about what may be happening out in the provinces," Henk Bekedan, director of the W.H.O. office here, said in an interview today.

The April 14, 2003 SARS update from the World Health Organization reporting new SARS cases in the Chinese northern province of Shanxi and in Inner Mongolia. This spread from the south to the very north suggests SARS is probably spreading throughout China.

China has today reported 109 new probable cases of SARS and 6 deaths, bringing the cumulative total to 1418 cases and 64 deaths. The largest number of cases occurred in Shanxi Province, where 47 new cases were reported. In addition, two provinces reported SARS cases for the first time – 10 in Inner Mongolia and 3 in Fujian. The reports indicate that the nationwide surveillance system, recently introduced by Chinese authorities, is working to detect and report cases. However, questions remain about the capacity of some provinces to cope with the challenge of SARS.

Shanxi was instructed only last week to start taking SARS seriously.

Today, officials in Shanxi said the province's local Center for Disease Control was instructed only last week to deal with SARS on an urgent basis. Only three hospitals in the province, all in the capital, Taiyuan, are able to handle SARS patients, officials said.

After 4 people travelling from Inner Mongolia showed up in the country of Mongolia to the north of China the Mongolian authorities responded by cutting off air and rail links to Inner Mongolian capital Hohhot.

The government said in a statement it had cut air and rail links to Hohhot for 14 days after four people with symptoms of the disease arrived from the capital of China's Inner Mongolia region, where three people have died of SARS.

Does anyone think there is the slightest chance that Mongolia and Inner Mongolia have the capacity to deal with SARS? This disease looks set to spread throughout the poorest parts of Asia. Now it is time to start looking for reports of SARS in Central Asia. Russia ought to start checking all rail and air passengers coming into Russia from China and Mongolia and ought to start checking those headed westward. But given how far SARS has already spread in China it seems only a matter of time before the disease spreads westward across China and into Tajikistan, Uzbekistan, and other countries in that region.

In spite of all this do you still feel optimistic that the spread of SARS can be halted? Well, South Africa wants rich Chinese tourists so much that it continues to encourage them to visit South African and it will not even screen them as they enter the country for signs of SARS.

Beijing - South Africa wooed Chinese tourists on Monday, saying they will not be barred from the country or subject to screening despite the spread of the deadly severe acute respiratory syndrome, or SARS, virus.

Picture SARS getting established in Africa spreading thru large populations of HIV sufferers with weakened immune systems. The lackadaisical South African government attitude toward SARS is grossly irresponsible.

The April 14, 2003 SARS update from the World Health Organization shows Hong Kong and China have 80 percent of all known SARS cases to date.

As of today, a cumulative total of 3169 cases of SARS, with 144 deaths, have been reported to WHO from 21 countries. This represents an increase of 213 cases and 25 deaths since the last update on Saturday. Indonesia, the Philippines, and Sweden report their first probable cases (1 in each country) today. Japan, which had previously reported four probable cases, was removed from the list as these cases were determined to have other causes. China, with 1418 cases and 64 deaths, remains the most seriously affected area. Hong Kong SAR, with 1190 cases and 47 deaths, is the second most seriously affected area. Three of the deaths in Hong Kong over the weekend occurred in persons under the age of 50, marking a departure from a previously pattern in which SARS caused deaths primarily in the elderly or in persons with pre-existing disease.

My guess is that China's SARS spread will accelerate while Hong Kong might be able to get it under control. The events in China may presage what will eventually happen in India, Africa, and other impoverished locales. If it gains a foothold outside of China in a poor country then SARS is very likely to become a pandemic.

One thing that Chinese health authorities ought to consider doing is to identify all people who have been exposed to and recovered from SARS. Then recruit those people to become health care workers to take care of SARS patients. Many of those who were infected with SARS in the first place were health care workers. So they already possess the needed skills. But the other recovered SARS patients could be trained in simple medical skills and work under the supervision of more skilled people who could tell them what to do.

A German biotech company has released the first SARS test which is based on the assumption that SARS is caused by a coronavirus.

The full coronavirus sequence will allow the development of faster, more accurate tests for SARS, using specific viral DNA fragments to prime PCR reactions. Early sequencing by the Bernhard Nocht Institute in Hamburg, Germany, has already helped the German firm Artus to produce a test that goes on sale on Monday.

The new Artus test takes only 2 hours.

The test can detect the virus from throat swabs, sputum or feces and produces results in two hours, say its makers, who specialize in disease test kits. They said classical tests for antibodies typically took 10 to 20 days after infection.

Because the Artus test uses polymerase chain reaction it is testing for SARS coronavirus DNA sequences.

A HAMBURG BIOTECH company will release a real time PCR (polymerase chain reaction) diagnostic test on Monday which, it is claimed, can diagnose SARS (severe acute respiratory syndrom) in two hours.

What is good about a PCR-based DNA test is that it can detect a SARS infection at a far earlier stage than an antibody-based test. Therefore this Artus test is very good news.

A cheap fast SARS virus DNA detection test has the potential to at least keep SARS from becoming a big presence in the industrialized countries. The SARS virus might achieve pandemic status worldwide and yet the industrialized countries could mount a vigorous long term defense using testing to keep SARS from becoming established in the industrialized countries. Testing could be done to all people entering industrialized countries thru legal ports of entry to identify people who need to be sent into quarantine. People could be held in customs until their tests were completed. Also, anyone showing SARS symptoms or exposed to someone with SARS could be quickly tested. However, illegal immigrants would still serve as carriers of SARS into industrialized countries. Also, there would still be false negative test results among those at the earliest stages of infection. Plus, all tests have error rates. Still, widespread testing could limit the presence of SARS in the industrialized countries until a vaccine becomes available.

By Randall Parker    2003 April 14 06:05 PM   Entry Permalink | Comments (0)
2003 April 09 Wednesday
Why So Many Disease Strains Come From China

Lots of new strains of influenza first show up in China. The reason is that tens of millions of humans live in close contact with a large variety of farm animals in conditions which encourage viruses to jump between species.

Dongxing is just one example of how Guangdong's 80 million people live close to the animals, poultry and fish they eat. At another piggery close to Mrs Yang's, a farmer keeps young chickens next to his pigs. All the piggeries empty their waste into the ponds where shrimp and grass-carp are raised for the table.

In other places, battery chickens are kept above the pig pens, feeding their waste into the pigs' food troughs. The close proximity and cross pollution adds to the risk of animal viruses infecting humans, either directly or via pigs

Of course it would be great if Chinese farming practices were changed in ways that would reduce the chances of viruses jumping between species. But the farmers who engage in the dangerous livestock raising practices are poor and do not have a lot of alternatives. As China industrializes one can expect conditions to improve as agriculture industrializes, becomes more capital intensive and less labor intensive. With fewer people down on the farm fewer people will come into contact with pigs, ducks, chickens, and other farm animals.

Given that China is such a threat as an origin of new pathogen strains and of pathogen species that jump between mammalian species it would also be great if the Chinese government was really eager to pursue proper public health policies for controlling epidemic disease outbreaks. However, as I explained in my ParaPundit blog posting Repressive Governments Make Fight Against SARS More Difficult the Chinese government, being a repressive regime that has lots of motives to cover up the truth, has plenty of reasons to mishandle an epidemic disease outbreak.

In spite of my previous readings and writings on why the Chinese government does what it does I was still floored to read that the Chinese government is currently trying to encourage domestic tourism as a way to assure international travellers that China is a safe destination.

Despite the risk of spreading the disease across this country, the government thinks that a successful May 1st holiday will help convince international travelers that China is safe, Chinese officials said.

Hong Kong is less an open society than it used to be but it is sufficiently open that scientists there are openly discussing the possibility that SARS will not be stopped.

Samson Wong, a microbiologist from Hong Kong University, said that Sars might infect 80 per cent of the population within two years and eventually everyone could be infected. A Health Department spokeswoman said that the possibility could not be ruled out but declined further comment.

What is making infectious disease experts less optimistic that SARS will be contained is the inability to trace some SARS cases to person-to-person contacts. This has led scientists to speculate that SARS may in some cases be spreading by cockroaches, sewage, contaminated surfaces such as door knobs, and by other means.

But in recent days, epidemiologists have been unable to trace a number of SARS outbreaks in hotels, hospitals and apartment complexes in Hong Kong, Singapore and China to such person-to-person spread.

In the face of such scientific uncertainty the Chinese government continues to be irresponsible in its handling of the SARS outbreak. It may become necessary for more governments to follow the example of Malaysia and start restricting travellers from Hong Kong and China.

By Randall Parker    2003 April 09 06:02 PM   Entry Permalink | Comments (0)
India, South Africa Reporting Suspected SARS Cases

Very few SARS cases have been reported in India so far. However, if SARS becomes established in India it will be very hard to stop.

"Our health system is very inadequate and it will be extremely tough to control the disease if it arrives," Anil Bansal, president of the Delhi Medical Association, told Reuters.

The very limited health case system in India makes the news about SARS coming from India very important. Therefore every suspected SARS case in India is watched very closely.

Not all suspected SARS cases in India have turned out to be SARS. For instance, Maria, the first suspected SARS case in New Dehli, may have a different kind of infection.

"She has been provisionally detected of having acute pharyngotonsilitis,’’ said Dr R.N. Salhan, the hospital medical superintendent.

Also, a 23 year old American woman suspected of having SARS in Bombay turned out to have a less dangerous illness. However there are at least two other suspected SARS cases in India including a 48 year old Indian national recently arrived via Singapore.

A 48-year-old software worker was admitted to hospital in Hyderabad on Tuesday after he arrived from Australia via Singapore with high fever, a cough and cold -- symptoms of the virus that has killed more than 100 people worldwide.

Surely the government of India can afford to quarantine and treat a few thousand sufferers. India is making efforts to be prepared to do so.

Facilities have been created for treatment of SARS cases in isolation in the Central Government hospitals as also in other Infectious Disease Hospitals. Health care facilities at International Airports and Ports have been strengthened by deploying additional doctors and evolving a standard operating protocol.

But the problem for India is that there are hundreds of millions of poor people who have little or no access to medical doctors and medical tests. If a single SARS sufferer reaches India and if that sufferer happens to be very infectious the results could be disastrous.

A single SARS sufferer is all it would take to rapidly cause a large SARS outbreak in a primitive country. "Hyper-infectors" (a.k.a. "super-carriers") of SARS may have been responsible for the big SARS outbreak in the Toronto Canada area.

Canada's SARS outbreak has been fuelled by three "hyperinfectors" who each passed on the disease to 20 or more other people -- a phenomenon never before seen with a virus, experts said yesterday

It is noteworthy that all three of the hyper-infectors in Canada died. Could it be that the more severe form of the disease is more infectious? Perhaps the people who have the severe form cough more and therefore generate more airborne particles which contain active virus.

It is unusual for a virus to be highly infectious.

Individuals who are inordinately infectious have been seen with certain types of bacteria, but not viruses, said Dr. Low.

Africa has the same vulnerability to SARS that India has. Therefore SARS cases in Africa are incredibly important to watch for. A Pretoria South African man who travelled from Hong Kong to South Africa on March 27 is hospitalized and suspected of being a SARS case.

A 62-year-old South African man is being treated at a Pretoria hospital as a "probable SARS" case, according to officials.

One factor that is doing a lot to reduce the chances of SARS spread is the great reduction in air travel. Given India's greater vulnerability to SARS Air India's 60% reduction in flights between Hong Kong and Bombay (Mumbai) is good news.

It further curtailed its services to Hong Kong, and will now operate only two flights a week (on Mondays and Fridays) as against the scheduled five flights a week.

While voluntary decisions to not travel are playing a role in efforts to reduce the risk of further spread of SARS government decisions can block off means of spread by more dramatic means. In order to reduce its risk of getting SARS cases from China the government of Malaysia is no longer granting tourist visas at its diplomatic facilities in China.

Malaysia has taken the draconian step of banning all tourists from mainland China to try to stop the spread of the deadly Sars virus.

India and Africa have greater need to take such a dramatic action than Malaysia does. If tourist travel was cut off other types of travel could still be allowed but under much more stringent rules. In the extreme, countries could allow passengers to travel from other countries but then force them into quarantine for 7 to 14 days upon arrival. This would provide a way for people who plan longer term changes in residence to still move around to take different jobs.

Update: On April 17, 2003 a confirmed case of SARS was found in Goa India.

Goa's chief minister, Manohar Parrikar said that a 32-year-old marine engineer had tested positive for the virus and was being treated at the Goa Medical College. The man is said to have arrived in Goa earlier this month after travelling in Singapore.

The worry has to be that this fellow may have already passed on SARS to other people after he returned to India. SARS may now be on the loose in India. If that is the case the odds of containing it there are low. If SARS becomes pandemic in less developed countries the effect on the world economy would be to cause world recession.

Update: India reports 2 new cases of Sars on Saturday April 26.

CALCUTTA, April 26 (Reuters) - A 42-year-old Indian man has tested positive for SARS, authorities said on Saturday, the country's sixth case of the virus that has killed at least 289 people and infected about 5,000 worldwide.

By Randall Parker    2003 April 09 03:53 PM   Entry Permalink | Comments (4)
2003 April 07 Monday
Search For SARS Cause Shows Power Of Gene Array Chips

The search for the cause of Severe Acute Respiratory Syndrome (SARS) has been greatly sped up by the use of DNA microarray gene chip technology. UCSF Assistant Professor Joseph DeRisi built a gene microarray containing all known completely sequenced viruses and used it to classify a pathogen isolated from SARS patients as a coronavirus.

DeRisi placed his computer's cursor over one lit dot and it read "bovine coronavirus." Another dot outputted "avian coronavirus." By the time he got to the turkey and human coronavirus dots, he knew he was dealing with something the world's scientists had never seen before.

If it had been a known virus — say the human coronavirus, a cause of the common cold — then only human coronavirus dots would have lit up.

DeRisi discovered that SARS is genetically most similar to a virus that infects birds.

Its genetic sequences so far seem to have the most in common with Avian Infectious Bronchitis Virus, according to preliminary molecular data obtained by Joseph DeRisi at the University of California at San Francisco and circulated among virologists.

Working with MIT post-doc David Wang and one other colleague (whose name I haven't been able to locate) DeRisi built a DNA gene microarray chip with the DNA of 12,000 different viruses. This allowed DeRisi to classify the suspected pathogen within 24 hours of the time he received a sample from scientists at the CDC. Let's put that in perspective. It took months to identify the pathogen that caused Legionnaire's Disease back in the 1970s. While DeRisi's assay was only one step of the process of isolation (it had already been tentatively identified as a coronavirus by viewing it with an electron microscope) it was a step that enormously accelerated the overall process.

DeRisi's development of a robot to place DNA samples onto the DNA gene microarray chip was helped along by advances made to do silicon semiconductor chip manufacture.

In fact, the robots that "pick and place" each sample from a small reservoir onto its spot on the slide are descendants of the machines used to build electronic chips.

This demonstrates a recurring FuturePundit theme: advances in electronic technologies are accelerating the rate of advance of biotechnologies.

The role that DeRisi and his colleagues played in identifying a coronavirus as a suspected cause of SARS came to the attention of the national media when CDC Director Dr. Julie Gerberding mentioned the work in a March 24, 2003 press conference.

But in addition, we're collaborating with academic partners. Earlier this week, we sent DNA out to a laboratory at the University of California, San Francisco, so that they could do the absolute state-of-the-art probe for virus genes and help us identify the cause.

Dr. DeRisi has made a more general contribution to the acceleration of the use of gene array technology. He built and released to the world the design of a robot that automates the process of putting DNA samples into gene arrays.

The technology behind the hope works by hybridization, the affinity for complimentary strands of DNA (cDNA) to form double helix structures. More than 40,000 unique DNA samples can be printed on glass slides in pre-determined locations.

DeRisi designed a robot that, at top speed, prints 14,400 elements per minute. These slides are then used to assay fluorescently labeled cDNA from tumors or organisms, like malaria, which are then stored on computers. Comparing these profiles can reveal the unique molecular signature carried by each type of cancer and give clues as to the original defect.

Despite the central role he played in revolutionizing genomics, it was DeRisi's populist approach to science that made him the buzz among academic and industry scientists. DeRisi never pursued a patent for the robot, instead he posted instructions on how to make it on the Internet.

"Joe could be a very rich man if he kept things to himself," says David Wang, a postdoctoral fellow in DeRisi's lab.

The lab maintains a website that disseminates protocols for the use of microarray technology while his UCSF site includes the instructions on building the robot.

What we still need are advances that will accelerate the rate at which vaccines can be developed. Vaccine development time for a disease like SARS is still measured in years. West Nile virus, for which vaccine development was begun in 1999, killed 277 Americans last year while leaving many others with central nervous system damage. Yet a vaccine for West Nile virus will begin undergoing preliminary testing on humans in June 2003, it is still three to five years away from general availability.

There's still a way that an infectious pathogen which is passed human-to-human like SARS can be defended against using biotechnology: be able to quickly and cheaply identify who is infected so that the infected people can be isolated. This can break the chain of infection and prevent a disease from developing into a pandemic. Without a test to identify exactly who is infected all people who have contact with an infected person must be put into quarantine regardless of whether they really are infected. Singapore has used this aggressive standard technique for epidemic control with considerable success. However, because an infected person can come into contact with a great many people who do not themselves become infected public health authorities are reluctant to quarantine them all. A test to identify people who are infected could make quarantine regimes far more acceptable and effective.

What is needed is a test that can identify infected people at a fairly early stage of the infection. Most of the SARS tests currently under development can not detect the infection at an early enough stage.

The development of a diagnostic test, which is being pursued around the clock by the WHO collaborating network of 11 laboratories, has proved more problematic than hoped. Three diagnostic tests are now available and all have limitations as tools for bringing the SARS outbreak quickly under control.

The ELISA detects antibodies reliably but only from about day 20 after the onset of clinical symptoms. It therefore cannot be used to detect cases at an early stage before they have a chance to spread the infection to others. The second test, an immunofluorescence assay (IFA), detects antibodies reliably as of day 10 of infection, but is a demanding and comparatively slow test that requires the growth of virus in cell culture. The presently available PCR molecular test for detection of SARS virus genetic material is useful in the early stages of infection but produces many false-negatives, meaning that many persons who actually carry the virus may not be detected – creating a dangerous sense of false security for a virus that is known to spread easily in close person-to-person contact.

What is needed is an advance in biotechnology that will provide a test for SARS with high sensitivity at a very early stage of infection.

(thanks to Hylton Jolliffe for the first link)

By Randall Parker    2003 April 07 10:04 PM   Entry Permalink | Comments (0)
2003 April 06 Sunday
Scientists Say SARS Spread May Be Inevitable

Experts in public health and infectious disease are beginning to say that they believe SARS is more likely to spread to pandemic levels than to be contained.

"Most people are hesitant to say it will just go away," said Dr. Ruth Berkelman, head of Emory University's Center for Public Health Preparedness and Research. "Too many people are infected to think we won't see it for a long time to come."

In an editorial in The New England Journal of Medicine US CDC Director Dr. Julie Gerberding thinks it would require extreme luck for SARS to be controlled.

"If we are extremely lucky, the epidemic will be curtailed, develop a seasonal pattern that will improve prospects for regional containment, or evolve more slowly than it has at this early stage," Julie Gerberding, director of the U.S. Centers for Disease Control and Prevention, wrote in an article this week.

"If the virus moves faster than our scientific, communications and control capacities, we could be in for a long, difficult race."

Note that her extreme luck scenario is for SARS to be controlled, not eliminated.

Dr. Donald Low (who is currently in isolation having himself been exposed to SARS) thinks SARS will become pandemic (i.e. widely spread).

"Unfortunately, it's an epidemic now that will become a pandemic," predicted Donald Low, chief microbiologist at Toronto's Mount Sinai Hospital.

Dr. David Heymann of the World Health Organization thinks we won't know whether we can contain SARS until we have a reliable test for infection.

"I think we've got to keep going at this speed until we get that diagnostic kit in use and figure out what's going on," Heymann said. "Then we'll know if we've lost or not."

One reason for the increased pessimism is the growing belief that some SARS sufferers are high infectious "super spreaders".

The four-member team is most interested in "the phenomenon of 'super spreaders' -- people who seem to spread their disease to a lot of other people," said the WHO team leader, Dr. Robert Breiman.

It is possible that co-infection with another pathogen makes a person into a "super spreader".

"It raises the question of, if you have one pathogen and you get hit with, say, coronavirus . . . are you more likely to transmit? Do you become what we call a 'super spreader?' " Breiman said.

Chinese scientists see evidence in some SARS sufferers of a rare airborne chlamydia bacteria that may be turning people into super spreaders.

Dr Robert Breiman, also of the WHO, said he feared people who already had chlamydia might be vulnerable to the flu-like bug and become highly contagious "super-spreaders".

Governments are moving to increase their quarantine powers. George W. Bush has signed an executive order giving public health officials the legal power to quarantine SARS victims. The Australian government has also moved to grant public health authorities power to force people into quarantine and even to close borders.

It seems likely at this point that decreased travel levels, use of facial surgical masks, and other responses to SARS will be longer lasting and spread to more locales. The economic cost of SARS then seems likely to increase substantially. If containment turns out to be impossible other defenses become more important.

Vaccines would be the ideal next line of defense but the very earliest we could expect help from a vaccine is a year from now. Since SARS is most likely a virus and anti-viral drugs are very difficult to develop the prospects on that front are not hopeful either. The best potential treatment is gamma globulin taken from the blood of people who have recovered from SARS. That may lower the fatality rate of SARS though likely only in industrialized countries and among elites in less developed countries. SARS could become pandemic in less developed countries and travel from those countries to industrialized countries could continually reintroduce it into the countries whose public health infrastructures allow them to stop its spread. Think of a series of fire alarms continually going off all across the industrialized countries as small outbreaks cause a series of small scale quarantines. That might turn out to be our future until a SARS vaccine is developed.

Another possible avenue of treatment is to find a way to suppress the most deadly symptom of SARS: the accumulation of fluids in the lungs which caused SARS to initially be called atypical pneumonia. The key to prevention of the fatal accumulation of fluids may be to find a way to suppress the production or sensing of the natural inflammation signalling compounds called cytokines. It is too early to tell whether steroids (which also suppress immune response) can suppress cytokines enough without suppressing the immune system too much.

With containment looking less likely, the availability of vaccines too distant in the future, and the development of drug regimens that prevent fatal consequences still in doubt the best response to SARS may turn out to be widespread changes in lifestyles and work habits to decrease the chances of spread. The widespread wearing of surgical masks as now seen publically in Hong Kong may spread to other areas where SARS takes hold. Health checks on airline passengers and the wearing of surgical masks on air flights might also become commonplace. The air filtration systems in many commercial and residential buildings may be quickly upgraded to prevent airborne virus spread.

Here's where the effect of SARS may become counter-intuitive: Because it kills only 3 or 4 percent of its victims a widespread public reaction that seeks to reduce the risk of exposure will have the added benefit of reducing the spread of influenza. This could lead to a net reduction in total deaths caused by infectious diseases because estimates of the yearly death toll in the United States from influenza run from 20,000 to 36,000 on average. The yearly death toll estimated as due to influenza in Canada runs from 1,500 to 4,500. Other industrialized countries have similar yearly death tolls from influenza proportionate to their populations. However, since influenza is more likely to kill the elderly the numbers also vary depending on the age distribution of the population and on the rate of yearly immunization. Also, death from influenza does not take as many total years of life away as a disease that strikes people down at a younger age. Still, if the populations of industrialized societies take drastic measures to reduce their risk of getting SARS one likely side effect should be a reduction of the death toll from influenza and possibly from other infectious diseases as well. Even those who are not at risk of dying from influenza will enjoy the benefit of being sick less often and employers will suffer lower amounts of lost work days and reduced productivity days due to sickness.

Update: A doctor in Hong Kong says Westerners fleeing Hong Kong are helping to spread the SARS virus more widely.

Dr David Stirling, told The Telegraph that families trying to escape the outbreak of the incurable illness - which has killed 80 people worldwide - were now the most likely reason for the spread of Severe Acute Respiratory Syndrome.

Update II: Time Magazine has an excellent article that compares the approaches used by Singapore and Hong Kong to respond to the outbreak of SARS. The far more aggressive measures pursued by Singapore resulted in the control of the outbreak.

When new cases were discovered, a team of 100 "contact tracers" tracked down not only patients' immediate families, friends and neighbors but also their office colleagues and favorite food hawkers, and placed them in quarantine, too. Anyone suspected of having SARS is transported to the hospital in an ambulance.

Singapore's far more aggressive approach toward identifying patient contacts and quarantining them has led to a decline in the number of new SARS cases in Singapore. It still may be possible to contain SARS if that aggressive approach is applied in other areas of SARS outbreak.

Update III: SARS may have gotten spread thru the Amoy Garden apartment complex in Hong Kong via cockroaches. If this turns out to be true then it will make SARS harder to contain.

By Randall Parker    2003 April 06 12:32 PM   Entry Permalink | Comments (1)
2003 April 05 Saturday
Experts Estimate SARS Vaccine Will Take Years To Develop

WHO deputy director Alan Hampson estimates SARS vaccine development time in years.

WHO deputy director Alan Hampson, said the disease could be like AIDS with treatments taking years to develop. "It would take years to develop an anti-viral drug," he said. "The earliest you can expect a vaccine is in a small number of years."

German scientist Reinhard Kurth estimates 3 to 5 years for SARS vaccine development.

Reinhard Kurth, the head of the German government's Robert Koch Institute, was not exactly encouraging on Friday night. A vaccine for Sars could be developed, he said – but it would take three to five years.

US National Institutes of Health NIAID director Anthony Fauci offers the best case timeline for SARS vaccine development of at least a year.

If it turns out that some other virus is at work, those researchers will have to start again, cautioned Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease. Even under the best-case scenario, he said, a vaccine is at least a year away.

Clearly, for the foreseeable future the only real option for the halt of the spread of SARS is to identify and isolate its victims quickly and to minimize the chances of exposure in locations where SARS is known to be present.

If you think SARS is bad just keep in mind that it does not spread as easily as influenza does. If SARS was caused by influenza tens of thousands would already be dead.

"If SARS were an influenza pandemic," says Melbourne University professor of virology, Ian Gust, "and the mortality rate was similar to what it is now (about 3.5per cent), we would have tens of thousands of people dead, rather than less than 100." And that is not because the virus would be any more potent, but because it would be much more contagious.

An extremely virulent form of influenza, the kind that only comes once every several decades, could end up infecting almost half of the population of industrialized countries. With a fatality rate similar to that of SARS it could easily kill one percent of the total population. The 1918-1918 so-called Spanish flu (which really didn't originate in Spain) With a world population at the time of 1.8 billion and with a low end estimate of the number killed by Spanish flu as 20 million the low end of the percentage of the population killed by the Spanish flu was at least 1 percent.

Although the history of flu epidemics is non-mathematical, in this case, as Voltaire might say, the superfluous is very necessary. In 1918, when the world population was 1.8 billion, an influenza epidemic incapacitated 1 billion and killed 20 million, all within the space of 8 weeks.

Higher estimates of the death toll from Spanish flu yield a death rate of at least 2 percent of the total world population.

The most intense, to date, occurred in the last year of World War 1: the so-called "Spanish Lady" or "Spanish Flu" pandemic of 1918-19 which infected one billion people, half the world’s population at that time, and killed between forty and fifty million. This makes it the most devastating disease of man known, surpassing even the bubonic plague of the fourteenth century, smallpox in the sixteenth century and the human immunodeficiency virus/AIDS pandemic that is happening now.

With a world population of 6.3 billion and a current annual growth rate of 1.16 percent a flu pandemic comparable to the 1918 Spanish Flu would kill somewhere in the range of 60 to 150 million people. This would be approximately equal to about one to two years of world population growth at current growth rates.

Given the fatality rate of SARS infections we are lucky that SARS is not as easily spread as influenza. Still, there is reason to be concerned about the spread of SARS because there are cases of SARS which do not fit the more optimistic model of a requirement of close contact for SARS to spread.

Five of the 24 cases of Sars (Severe Acute Respiratory Syndrome) in the southern Chinese city of Foshan examined so far by a newly-arrived World Health Organization (WHO) team were caught despite the patient having no obvious contact with an infected person.

The biggest defense we have against a highly deadly influenza pandemic is the speed with which influenza vaccines can be developed against threatening new influenza strain.

(MEMPHIS, TENN.--April 2, 2003) Scientists at St. Jude Children's Research Hospital announced today the development of a vaccine against H5N1, a new lethal influenza virus that triggered the World Health Organization (WHO) to declare a pandemic alert in February 2003.

The virus appeared in birds in Hong Kong late last year and subsequently killed one of two infected people with rapidly progressive pneumonia in the past month. St. Jude developed the vaccine in only four weeks from the time it received the H5N1 sample from colleagues in Hong Kong.

The announcement comes at a time when a second, as-yet-unidentified virus, has taken several lives around the world. The unknown virus, which causes severe acute respiratory syndrome (SARS), appears to have originated at the same time and in the same place as the new "flu."

The development of the initial ("seed") batch of H5N1 vaccine is significant because humans do not have a natural immunity to the virus, according to Robert Webster, Ph.D., a member of the Department of Infectious Diseases at St. Jude. Rather, humans appear to become infected through contact with chickens and other birds. In the past the virus killed only the chickens it infected. But the new variant of H5N1 also killed many kinds of wild birds, which is unusual.

Even if a new vaccine could be developed rapidly to counter a killer influenza outbreak the problem today is that there would not be enough production capacity to make influenza vaccine for everyone. However, as demonstrated in US Health and Human Services Cabinet Secretary Tommy Thompson's March 27, 2003 testimony to the US Congress House Committee on Energy and Commerce & House Select Committee on Homeland Security the United States government is funding research to develop vaccine production technologies that are more easily scalable than current vaccine production techniques.

For example, the President's budget foresaw and prepared for an influenza outbreak. It proposes to spend $100 million to ensure the nation has an adequate supply of influenza vaccine in the event of a pandemic. Due to the constant changes in the circulating influenza strains, we cannot stockpile influenza vaccine, and the current manufacturing methods might not meet the Nation's needs in the event of a pandemic.

Funds will be used for activities to ensure a year-round influenza vaccine production capacity and the development and implementation of rapidly expandable production technologies. We will work closely with industry to accomplish these goals.

More scalable vaccine production techniques also have obvious anti-bioterrorism applications. Therefore the development of better vaccine production capabilities have been given an added spur by the rising awareness of the threat of bioterrorism.

By Randall Parker    2003 April 05 07:01 PM   Entry Permalink | Comments (6)
2003 April 04 Friday
Impressive Handling Of First American SARS Case

Three months after SARS first appeared in China but almost a month before it started causing deaths in Hong Kong a Loudon County Virginia woman recently returned from Guangdong province China came down with what appears to have been the first American case of SARS (Severe Acute Respiratory Syndrome). On February 17 2003 after showing up in the emergency ward of Loudoun Hospital Center she was placed in a sealed room and the health care workers who treated her work protective gear in order to avoid infection.

In the emergency room, she had a high fever and a cough and was having trouble breathing. She and a relative mentioned that she had been in Guangdong and that a flu seemed to be going around there. A triage nurse put the woman in a sealed room that had a dedicated ventilation system to prevent her from passing along the infection.

The details of how she was handled read like a textbook approach for how to handle an unknown and potentially dangerous infectious illness. The Loudoun Hospital Center folks had the assets needed and made the right call.

By Randall Parker    2003 April 04 05:11 PM   Entry Permalink | Comments (0)
Chinese Government Faulted For Making SARS Outbreak Worse

The Washington Post has a good report laying out the events inside the Chinese government as it covered up the outbreak of SARS.

The outbreak of the illness is a revealing case study in how China's authoritarian government, which seeks to maintain a monopoly on power and control information, concealed vital data about a life-threatening disease from the Chinese people, according to doctors, health officials and journalists familiar with the events.

China is the place where the holding back of information on epidemic outbreaks promises to be most threatening to the world as a whole. Because of the millions of people (tens of millions? hundreds of millions?) in Southern China who live in close proximity with pigs, ducks, and other fowl China is like a big experiment for the mixing of DNA across different virus strains that normally infect different species. In the case of SARS it is likely that a human coronavirus coinfected a cell (probably in a human) at the same time a coronavirus from another species did as well. Genes were exchanged and the result was a coronavirus that is more lethal to humans. This also happens with influenza viruses. The most lethal influenza viruses are either viruses that jumped over from other species or which exchanged DNA with viruses from other species.

Because China has such ideal conditions for gene swapping between virus strains from different species it is more likely than any place on Earth to be the source of the next killer virus whose lethality would rank up there with the 1918-1919 Influenza pandemic that killed 20 to 40 million people. The authoritarian impulses of the Chinese authorities to control and hush up bad news, as they have done with the SARS pathogen, put the rest of the world at much greater risk to every new disease that first shows up in China. This impulse on the part of the Chinese government deserves to be widely and loudly criticised. The rest of the world needs to make it clear to China that this kind of "hush it up" reaction to disease outbreaks will not be tolerated because it creates an unacceptable risk to the health of all of humanity.

While the Chinese government prevented Chinese newspapers from reporting on SARS Dan Gillmor reports that text messaging using mobile phones helped spread the knowledge that SARS was a threat.

I found the Dan Gillmor link in a SARS link collection by Ian Mckenzie.

Update: Health care workers in Beijing are reporting 50 cases of SARS in spite of the fact that the last report from China to the WHO reported only 12 in Beijing. China is still being slow about admitting the extent of its SARS cases.

The additional cases have not been reported to the World Health Organization, even though Chinese health officials promised to begin daily reporting of such statistics this week.

Update II: The Globe and Mail has an excellent story on how the Chinese government tried to keep secret the spread of SARS.

But information was not shared with other health departments in this province of 80 million people. Instead, the Heyuan paper printed this statement on Jan. 3 from the local health bureau: "No epidemic disease is being spread in Heyuan. . . . Symptoms like cough and fever appear due to relatively colder weather." That was apparently the first report on SARS in the Chinese media.

Update III: In a move that is extremely rare for China the director of the Chinese CDC apologized for the Chinese government's handing of SARS.

"Today, we apologize to everyone," said Li Liming, director of the Chinese Center for Disease Control. "Our medical departments and our mass media suffered poor coordination," he said. "We weren't able to muster our forces in helping to provide everyone with scientific publicity and allowing the masses to get hold of this sort of knowledge."

While this apology has been broadcast in Hong Kong it is not clear whether people in mainland China heard it.

Li's statement was not immediately reported by Chinese media. It was not known whether his remarks were authorized by senior officials or whether Li, highly regarded in his field, had taken the unusual step of articulating the widespread view on his own. Other officials who have released unauthorized material about SARS have lost their jobs

In an encouraging sign that the Chinese leaders have perhaps learned that they can't go keeping major disease outbreaks secret the Chinese Deputy Prime Minister made noises about being a lot more open the next time around.

Deputy Prime Minister Wu Yi called for "the immediate establishment of a national medical emergency mechanism, with emphasis placed on a public health information and an early warning reporting mechanism".

By Randall Parker    2003 April 04 11:57 AM   Entry Permalink | Comments (1)
2003 April 03 Thursday
Why SARS Death Rate Lower In United States

There are 100 suspected cases of SARS (Severe Acute Respiratory Syndrome) in the United States with no deaths reported so far. By contrast, as of April 3, 2003 the World Health Organization has reported a cumulative total of 2270 SARS cases and 79 deaths.

Chinese authorities had previously reported a cumulative total of 1153 cases and 40 deaths in Guangdong Province from 16 November, when the outbreak began, to the end of March, making this province the area most seriously affected by SARS to date.

...

As of today, a cumulative total of 2270 SARS cases and 79 deaths have been reported from 16 countries. This represents an increase of 47 cases and 1 death (in Hong Kong) compared with yesterday.

Why the different death rates? Is the lower US death rate a reason to be complacent? Probably not. One reason is that US Centers for Disease Control and Prevention uses a different set of rules for identifying suspect SARS cases.

The majority of U.S. residents with SARS have recovered or stabilized clinically without specific antiviral therapy. The U.S. case-fatality proportion is lower than that reported in some other countries (3). Possible explanations for this include differing case definitions among countries or differences in the sensitivity of surveillance, leading to identification in the United States of patients with less severe or early manifestations of infection or of a larger proportion of patients with other respiratory illnesses. Until confirmatory laboratory testing is available, the case definition will include clinical criteria more likely to identify potentially infectious persons. Various therapies, including antiviral agents (e.g., oseltamivir or ribavirin) and corticosteroids, have been administered to SARS patients, but the efficacy of these therapies has not been determined.

Director of the CDC Dr. Julie Gerberding provides additional background on US CDC versus WHO SARS classification rules.

But with respect to your second question, why are the case patients in the United States having relatively mild illness, this is a conscious decision on our part to include anybody with fever and a respiratory symptom who had traveled to an affected area. The cases that WHO is including from countries on its list--at least most of the cases that are formally appearing on the WHO list--are only people who have the severe form of SARS, with the pneumonia. And so we are casting a broader net in this country because we want to be vigilant about identifying anyone who could possibly be infectious, and isolating them if they're sick, and advising their contacts how they can protect themselves. So not surprisingly, we do not have as many patients with pneumonia. In fact, I think we have altogether--I'll have to get back to you on the exact number, but less than 50 percent of our case patients have had pneumonia. And one of our case patients has required ventilation. But most of that is the artifact of the way in which we are conducting our evaluation and our epidemiologic assessment. Actually, about 20 of the case patients have been diagnosed with pneumonia.

Once an accurate test for SARS infection becomes available (and it looks like scientists are fairly certain that a coronavirus is the cause) then methods of classifying SARS victims can become more uniform. Dr. James Hughes of the CDC reports on progress in the development of SARS tests:

DR. JAMES HUGHES: In terms of the serologic testing, realize that 10 days ago we didn't have any antibody test to detect evidence of infection with this previously unrecognized corona virus. As a result of a lot of hard work that's been done here over the past 10 days, we now have two that look promising. One is an indirect fluorescent antibody test, and the other is an Eliza. More work needs to be done to validate these tests. I would remind you that these are tests that are not approved for routine use for patient diagnosis yet--not surprisingly, since they've just been developed. So we have to interpret results using these tests with caution. Having said that, they look promising in that they appear to perform well in suspect cases, particularly a subset of those that are relatively more severe. We have looked for evidence of this antibody in roughly 400 sera collected recently from people in this country without any suggestive evidence of SARS, and they're negative in all of those people.

If the indirect antibody test measures immune response to the virus (not sure, does anyone know?) it could be very useful for identifying recovered victims who no longer have the SARS virus in their bodies. This would be incredibly helpful because people whose immune systems have fought off the SARS virus could be used as blood donors to extract gamma globulin immune system molecules from their blood. The gamma globulin can be used to treat the most severe cases of SARS.

Whether SARS is eventually controlled continues to strike me as being heavily dependent on whether it reaches less developed places where the public health infrastructure is nearly non-existent. Let it get loose in India and it seems like it would become impossible to control.

By Randall Parker    2003 April 03 02:25 PM   Entry Permalink | Comments (1)
2003 April 02 Wednesday
Silent Carriers May Be Spreading Severe Acute Respiratory Syndrome

A forthcoming New Scientist article reports the greatest fear of SARS (Severe Acute Respiratory Syndrome) researchers is the possibility of asymptomatic "silent carriers" may make SARS uncontainable

But if people can harbour and transmit the virus while while remaining healthy, or showing few symptoms, it will be much harder. "If there are silent carriers, it will be virtually impossible to contain," warns Osterhaus. This issue is now the focus of research, says Heymann. A lab test for SARS would give a huge boost to surveillance and containment efforts.

If the disease reaches India or some other country where few people have access to an organized healthcare infrastructure then the disease is going to be extremely difficult to contain anyhow. We could quickly reach a point where many countries stop allowing travel from countries where the disease is spreading unchecked.

Some people may not be entirely asymptomatic but they might have symptoms too mild to cause a person to seek medical attention.

Lucien Abenhaim, who as director-general for health is France's equivalent of surgeon-general, noted however "we know now that there are minor forms of the illness," meaning that people can be infected but have only minimal symptoms.

Hopefully the silent carrier fear will not pan out. But even if it doesn't it is by no means assured that SARS can be contained at this point.

SARS demonstrates the value of speedier methods to isolate and characterize pathogens. Technologies under development to make nanodots and other nanotech sensor approaches for biological material promise someday to speed up the development of defenses against new infectious agents by orders of magnitude. Advances in biotech are already evident in the response to SARS. It took many months to identify and characterize the cause of Legionnaire's Disease back in the 1970s. The pace of the advance in the SARS investigation has been much more rapid. The scientists working on the cause of SARS have already focused their attention on a coronavirus after an initial suspicion that a paramyxovirus might be the cause. Now scientists are reporting that SARS might have been come about from the mixing of DNA from coronaviruses from different mammalian species.

Canadian scientists racing to find the cause of SARS say it appears to be a mutant strain of coronavirus with bits of human, cow and mouse virus scrambled into its genetic code.

The likely way this happened was that a single animal or human was infected by human and animal coronavirus strains at the same time. Different kinds of coronavirues in the same cell swapped genes to create a new and more virulent hybrid. Separately, other scientists have shown that cross-species mixing of coronaviruses can create new and more infectious forms of virus.

Now, in a simple overnight experiment, researchers transformed a coronavirus that is lethal to cats into one that infects mouse cells by replacing a single gene1.

The genetic code of the coronavirus that is suspected of causing SARS is expected to be approximately 30,000 DNA base pairs in length. Scientists are working with isolates of the SARS coronavirus to sequence it. Once it has been refined into a pure enough form to be DNA sequenced the current equipment for DNA sequencing could read its code within a single day. However, sequencing is normally done several times to check for errors and so this process can take a week or two. Where we are still lagging in speed is in the ability to then develop a vaccine or drug that can counteract the effect of SARS. The best prospect for development of an anti-SARS treatment in the short term is in the isolation of gamma globulin from the blood of those who have recovered from the disease.

Although no drugs have proved useful in treating the viral infection, Dr. Leung Ping-chung of Prince of Wales Hospital said Monday that doctors used gamma globulin from recovered patients to treat 20 severely affected victims

The success of the gamma globulin treatment raises the prospects of being able to reduce SARS deaths in industrialized countries should SARS reach pandemic levels.

The rate of scientific progress in investigation of the cause of SARS might be fast enough to stop the spread of the disease because tests may be developed to speed its detection. Though that the containment of SARS is by no means assured. Even if we manage to dodge the bullet this time there is no reason for complacency. If an influenza (which is probably more easily transmissible) of equal or greater lethality was to pop up then the odds of containing it with current technology and current public health practices would be much lower. Therefore even in the industrialized countries humanity remains quite vulnerable to new and more lethal forms of natural pathogens.

The New Scientist has a worthwhile SARS theme page with all their SARS articles.

Update: You can find all of the FuturePundit SARS posts in the Natural Dangers category archive. Also, you'll find my coverage of the economic impacts of SARS on my ParaPundit blog in the Political Economics category archive

Update II: To clarify: Note that in the event of an outbreak of SARS into wider populations that while gamma globulin may be able to save many lives in industrialized countries SARS would exact a far higher toll in less developed countries. Also, as is being demonstrated in East Asia right now the economic consequences of a SARS pandemic would be enormous. I've been posting a lot on SARS because its like we are out there on the edge of a precipice and it is not yet clear whether we are going to take the plunge.

By Randall Parker    2003 April 02 03:35 PM   Entry Permalink | Comments (3)
WHO Advises Against Hong Kong, Guangdong Travel

Reacting to the spread of the new infectious disease Severe Acute Respiratory Syndrome (SARS) the World Health Organization has advised against travel to Hong Kong and Guangdong province of China.

Wednesday, 2 April, 08:30 Palais des Nations

World Health Organization

Dr David Heymann, Executive Director, Communicable Diseases

Dr Guenael Rodier, Director, Communicable Disease Surveillance and Response

Mr Dick Thompson, Communications Officer

Mr Dick Thompson
This will be an abbreviated press briefing. You will have an opportunity to ask a few questions, but not many. The reason is that they are getting on a flight to attend Carlo Urbani's funeral in Italy.

Statement from Dr David Heymann
Good morning. Thank you for coming this morning. We have two different types of information to offer to you this morning. The first is that China is now a full partner with WHO. The teams have been asked to immediately go to Guangdong. Guangdong has reported the number of cases that have occurred during the month of March, which is 361 cases and 9 deaths, which mean that the epidemic is still going on in Guangdong, and they have promised that later today they will provide all of the information that they have obtained from their national disease surveillance system looking for SARS. So we are very pleased to announce that China is now a full partner with other international partners, in fact with the rest of the world, in collaborating on stopping this epidemic and in finding out the various aspects that we need to find out.

The second [type of information] is that since control measures have begun in Hong Kong, which began on 15 March, just after we made our announcement, and in other parts of the world, control measures have been successful in stopping the disease. For example, in Viet Nam the disease has been stopped we believe. In Singapore and Toronto, activities are going on and they are having good success.

I would like to focus now on Hong Kong, however, where since 15 March there have been 9 people, travellers, tourists or businessmen, from Beijing, from Taiwan, and from Singapore, who have returned home from Hong Kong infected with SARS. In addition in Hong Kong, they have found that transmission does not seem to be only by close contact from person to person. It appears that there is something in the environment that is transferring virus, which is serving as a vehicle to transfer the virus from one person to another. We do not believe this is the air. We believe that it is something else in the environment and we have talked about that in past press conferences. It is possibly an object that people are touching and getting infected from, where there has been a SARS patient who has coughed, or possibly a sewage system or a water system or some type of environmental vehicle that takes the virus from a sick person to others. So we see clusters of cases where there is one case, for example, living in an apartment building, where other people in that apartment building have been infected.

So for these two reasons, because of the fact that we do not completely understand the means of transmission in Hong Kong, and because since the 15 March tourists and businessmen have returned from Hong Kong to their countries with infection, we have decided to make a recommendation that people who are planning travel to both Hong Kong and Guangdong, which as you know is adjacent to Hong Kong, consider postponing their travel until another time. We will be working daily with the Hong Kong authorities, and we have daily conference calls with them and now we will begin also with Guangdong authorities, to determine if there are any reasons that we can stop that recommendation. In other words, the recommendation will be reevaluated every day and we will make a decision every day whether or not that needs to be changed. So now what we have is from all sites where there is a SARS outbreak that is causing chains of transmission, we have requested that tourists or travellers understand about the disease, that airports screen passengers who are returning to their countries from these sites, and now, in addition, we are telling travellers who are planning to go to Hong Kong and Guangdong that they consider postponing their travel. So what we have is a system in place now which will, we hope, stop the spread from the sites where SARS is occurring internationally and at the same time help passengers, tourists or businessmen who are planning to go to Hong Kong or Guangdong decide better whether or not they should go. We are recommending that they reconsider their travel plans and postpone if possible their travel to Hong Kong or Guangdong.

It is noteworthy that SARS has not been contained in China. The Chinese claimed they had it under control. Instead it has been spreading. China appears to finally be cooperating with the WHO. But the Chinese authorities have been quite irresponsible up to this point. The disease first showed up in Guangdong province China in November 2002. If the world's infectious disease experts had been notified at that time we'd be about 5 months further along in the learning curve about this disease and containment measures to stop international spread would have been begun much sooner and with much greater success.

Some countries are taking more drastic action. If travelling from Hong Kong to Thailand you will be placed in quarantine when you reach Thailand.

Q. Yes, Dr Heymann, can you explain a little bit about the process prior to issuing this advice? While it probably makes sense from the health perspective, it will have economic, social, political impact in the region. I’m wondering if you have consent from authorities in Guangdong, Hong Kong, or China?

A. Dr David Heymann: We’ve spoken first of all with IATA, which is the International Air Transport Association, and they have understood this and they have given their agreement that this is the recommendation which should be made at this point. We’ve discussed with the various different countries in the region, with our regional office and through our regional office, and we find that in those countries there are already much more strict recommendations than this is. For example, in Thailand, the government has announced that all returning passengers from Hong Kong will be quarantined. So we understand that there are very serious measures already being taken in many countries. So we made this decision with countries, with WHO and, more importantly, with our expert group of advisers on travel and health. We’ve spoken with many of our advisers, you know we have various advisers around the world, we have talked with them as well. And through all of these discussions, which went on all day yesterday and the day before, we’ve come to this conclusion.

The economic consequences of SARS could grow very large. Of course the tourist industry will be hit. But also various business meetings that facilitate international trade will not take place.

Update: This WHO recommendation is unprecedented. The World Health Organization has never before in its history totally recommended against travel to a specific geographic area.

This is the first time in the history of WHO that such travel advice has been issued for specific geographical areas because of an outbreak of an infectious disease.

Since 1958, WHO has issued weekly lists of areas infected with quarantinable diseases so that national authorities can decide whether to apply public health measures to arriving travellers. During the last years of the smallpox eradication campaign cases spread internationally by land. Controls at borders between neighbouring countries were relied on to prevent international spread. No global recommendations were necessary.

Here is the World Health Organization press release for the travel advisory: Update 17 - Travel advice - Hong Kong Special Administrative Region of China, and Guangdong Province, China

The SARS situation in Hong Kong Special Administrative Region has developed features of concern: a continuing and significant increase in cases with indications that SARS has spread beyond the initial focus in hospitals. These developments have suggested environmental routes of transmission from a SARS infected person which may be related to contamination of common systems that link rooms or flats together. Despite the implementation of strict measures to control the outbreak, there have continued to be a small number of visitors to Hong Kong who have been identified as SARS cases after their return from Hong Kong. The epidemic in Guangdong Province of China, situated adjacent to Hong Kong, is the largest outbreak of SARS reported and has also shown evidence of spread in the wider community. As a measure of precaution WHO is now recommending that persons travelling to Hong Kong and Guangdong Province of China consider postponing all but essential travel. This temporary recommendation will be reassessed in the light of the evolution of the epidemic in the areas currently indicated, and other areas of the world could become subject to similar recommendations if the situation demands.

Please note that this recommendation applies only to travellers entering Hong Kong Special Administrative Region of China and Guangdong Province of China, not to passengers directly transiting through international airports within those areas.

By Randall Parker    2003 April 02 09:54 AM   Entry Permalink | Comments (1)
2003 April 01 Tuesday
Fears Grow That SARS May Spread Into Pandemic

Initially when the new infectious disease SARS (Severe Acute Respiratory Syndrome) emerged early indicators were that it was not easily transmissible. The first indication that it might be more easily transmitted was the discovery of its transmission from one doctor to several people who stayed on the same floor of the Metropole Hotel in Hong Kong. As SARS continues to spread a consensus is emerging that SARS is much more easily transmissible than originally thought. Suspicions that it is caused by a coronavirus strengthen this belief because about one third of all colds are caused by coronaviruses and of course colds are fairly easily transmitted.

The World Health Organization reports on the spread of SARS in Hong Kong.

The Hong Kong Department of Health has today issued an unprecedented isolation order to prevent the further spread of Severe Acute Respiratory Syndrome (SADS). The isolation order requires residents of Block E of Amoy Garden to remain in their flats until midnight on 9 April.

The decision to issue the isolation order was made following a continued steep rise in the number of SARS cases detected in the building over the past few days. Concern about a possible outbreak in Amoy Garden mounted on Saturday, when 22 of Hong Kong’s 45 new SAR cases hospitalized that day were determined to be residents of the estate. On Sunday, 36 of the 60 new patients admitted to hospital with probable SARS were Amoy Garden residents.

Hong Kong health authorities today informed the public that a cumulative total of 213 residents of Amoy Garden had been admitted to hospital with suspected SARS since reporting on the disease began. Hong Kong’s outbreak began on 12 March when health officials first recognized a cluster of cases of atypical pneumonia in the Prince of Wales Hospital.

Of the 213 Amoy residents affected in the outbreak, 107 patients resided in Block E. In addition, most of these 107 patients from Block E lived in flats that were vertically arranged.

This suggests that SARS may be spreading in Hong Kong according to a different pattern, still involving close person-to-person contact with bodily secretions from an infected person. WHO epidemiologists are considering the possibility that bodily secretions containing the causative virus might somehow enter common systems that link rooms or flats together. This pattern of spread would be in addition to the well-documented face-to-face contact that has been seen in the majority of cases reported so far.

Earlier this month, Hong Kong epidemiologists detected an unusual pattern of transmission among guests and visitors at the Metropole Hotel during the critical period of 15 to 23 February. Guests and visitors at a single floor of the hotel are thought to have spread SARS to Toronto and Singapore and to have started the outbreak in Hong Kong’s Prince of Wales Hospital. No staff at the hotel developed symptoms

The guests of the Metropole Hotel who got SARS all stayed on the same floor of the hotel. This again suggests spread of the disease via air ducts.

If ducts in the Amoy Garden building are spreading SARS then quarantining the people of that apartment building and forcing them to stay inside may well turn out to be a death sentence for some of them. The ones who are not yet infected will be forced to remain close to those who are infected but not yet diagnosed. Therefore the spread of the disease within Amoy Garden may continue.

If the disease continues to spread and more quarantines are ordered then it is quite possible that people will resist being quarantined in close quarters with other people who might be infected. The Amoy Garden quarantine is already being enforced by police stationed outside to prevent people from entering or leaving.

The Hong Kong housing block, the Amoy Gardens in Kowloon, was surrounded by about 50 police officers on Monday, as the Hong Kong authorities invoked quarantine laws to try to stem the growing crisis.

In a really large scale outbreak there would not be sufficient numbers of police available to enforce quarantines. If the connection between SARS spread and air ducts is established then in the event of a large scale outbreak many people will likely flee from multi-unit dwellings such as apartment buildings.

While SARS spread on a single floor in the Metropole Hotel the pattern of SARS spread in the Kowloon apartment block is different

"They are finding that the infections are in people living in apartments on top of each other, only in one area of this apartment block. It's only two apartments, but from floor zero to 35. Not all of those apartments are affected, but most of the families affected are living in that small area of that apartment building," virologist Klaus Stohr said at WHO headquarters in Geneva.

One potential explanation for the difference in the pattern of spread in the Metropole Hotel and the Amoy Garden may be a different duct work layout. Ducts might be laid out in a more columnar structure in the Amoy Garden and more in rows in the Metropole.

If, as suspected, SARS is caused by a previously unidentified member of the coronavirus family then it is probably similar to other coronaviruses and possesses the ability to survive on exposed surfaces for a few hours at least. Therefore it might be transmissible by touching a surface at a location where an infected person coughed a few hours previously. Frequent handwashing may help to reduce its spread.

By the end of March 2003 there have been 1622 reported cases of SARS and 58 deaths. That is a nearly 4% death rate. But the actual death rate is likely even higher since some of the currently infected out of the 1622 will eventually die from the infection.

SARS Kills People In The Prime Of Life

While most types of influenza tend to kill only the very old, the very young, and those who are immuno-compromised SARS kills people in the prime of life.

Dr. Carlo Urbani, an expert on communicable diseases, died today of SARS. Dr. Urbani, worked in public health programs in Cambodia, Laos and Viet Nam. He was based in Hanoi, Viet Nam. Dr. Urbani was 46.

The great influenza pandemic of 1918-1919 (popularly known as the Spanish Flu) also struck down those in the prime of life. Though while Spanish Flu caused the highest mortality rate in those aged 20-39 WHO official Mark Salter says the risks of dying from SARS are greater for those over 40 years old.

Age could be one factor, with people over 40 apparently at greater risk, while the fact that a patient was already suffering from some other chronic ailment, such as heart or liver disease, could also play a part, he said. "The indications seem to be that if the patient is over the age of 40 and has other illnesses as well...they would be more prone to developing a more severe form when the chances of survival become smaller," he told Reuters.

SARS May Spread As Easily As Common Cold

Here are excerpts of the March 29, 2003 CDC press conference held by CDC director Dr. Julia Gerberding. (bold emphases added)

We believe, based on what the investigations have shown us so far, that the major mode of transmission still is through droplet spread when an infected person coughs or sneezes and droplets are spread to a nearby contact. But we are concerned about the possibility of airborne transmission across broader areas and also the possibility that objects that become contaminated in the environment could serve as modes of spread.

Coronaviruses can survive in the environment for up to two or three hours ,and so it's possible that a contaminated object could serve as a vehicle for transfer to someone else.

In health care settings, we have already initiated guidance to protect against droplets, airborne and contact spread of this virus, and today we're issuing an update on how to protect people in homes of SARS patients.

We know that the individual with SARS can be very infectious during the symptomatic phase of the illness. We don't know how long the period of contagion lasts once they recover from the illness and we don't know whether or not they can spread the virus before they have the full-blown form syndrome.

But most of the information that the epidemiologists have been able to put together suggests that the period of contagion may begin with the onset of the very earliest symptoms of a viral infection, so our guidance is based on this assumption.

About one third of all common cold infections are caused by a type of coronavirus. Hence Dr. Gerberding makes a comparison to cold virus spread.

DR. GERBERDING: We are very vigilant about the possibility of spread. We recognize that there are at least some patients with SARS that are extremely efficient transmitters. We don't know to what extent all patients are particularly infectious but there are clearly some who appear to be very highly infectious, and, for example, in Hanoi where there was one patient who was a source for health care worker transmission and approximately 56 percent of the health care who had direct contact with the patient appeared to have acquired SARS.

So given that high degree of contagion and what we know about spread of cold viruses, I think we are very alert to the possibility that this could spread outside of the confined populations that I've mentioned, travelers to the affected areas, close household contacts, and health care workers. But we are not seeing that now and we are looking for it very closely.

So if we begin to appreciate that, we will have to expand our recommendations to be more inclusive of special protective measures for contacts.

The biggest danger is that SARS is spreading in places that are effectively out of sight of Western investigators. The most likely country where SARS is still spreading is China. Western disease experts still have very little visibility into what is really happening with SARS spread in China.

DR. GERBERDING: Well, from the standpoint of CDC, I would say that we are very concerned about the spread of this virus, particularly in Asia. We recognize this as a epidemic that's evolving differently, in different geographies, but nevertheless, it is a respiratory virus, it does appear to be transmitted very efficiently, and what we know about respiratory viruses suggests that the potential for infecting large numbers of people is very great.

So we may be in the very early stages of what could be a much larger problem as we go forward in time. On the other hand, this is new, we don't know everything about it, and we have a lot of questions about the overall spread.

The patterns of transmission in the individual countries vary, depending on where the primary foci of transmission is occurring.

In Hong Kong, the situation is particularly alarming because we have several hospitals that are affected, and there are so many health care workers in each of these hospitals that could have been exposed or who are developing SARS, that there's already a multiplier in the community. Every health care worker has household contacts, those contacts, when they become ill, have had other exposures.

So we are very concerned about the speed and the amplification process in Hong Kong. On the other hand, the health officials there are taking extremely efficient and aggressive steps at this point in time to contain spread in that community, including closing schools and closing hospitals, and cohorting health care workers and patients.

So it remains to be seen whether or not those measures will attenuate the spread. The biggest unknown is of course what is going on in China and we are desperate to learn more about the scope and magnitude of the problem there, because that really I think will be the biggest predictor for where this will be headed over the next few weeks.

Here we are over 5 months after the SARS disease first surfaced in China and CDC and WHO authorities still know little about how the disease developed and spread in China. As a consequence of our ignorance of the disease's spread in China we have only the information developed from the course of its much more recent appearance in Hong Kong and in places outside of China. Therefore we simply do not yet know enough to say what are all the ways by which SARS can be transmitted.

Concerns that I mentioned earlier focused on droplet transmission, so if you were in the elevator and an infectious person literally coughed on you, it's conceivable that you could acquire a respiratory infection, including SARS, through that mechanism.

On the other hand, most of the information suggests that fairly prolonged contact, on a face to face basis, is typical of the transmissions.

There are anecdotal reports, that we haven't confirmed yet, of much briefer contact. There's been a concern expressed about the potential for airborne or surface contamination in the apartment in Hong Kong, and these are all open questions that we are aggressively pursuing here.

It could be worse. A moderately severe influenza strain (i.e. not as bad as the 1918 outbreak but worse than the average influenza strain) has a higher mortality rate than SARS. Though influenza tends to take the very young and very old and hence elicits less fear in the general population.

DR. GERBERDING: Certainly, there could be other cofactors involved such as viruses or underlying illness, but this is just atypical pattern for any infectious disease. If you get pneumococcal infection, many people have completely asymptomatic. Some people get a mild disease and some people have a full blown, very, very severe illness from the infection.

So this is a typical pattern for respiratory illnesses, not something that we're surprised about. In fact if there's any good news in SARS right now, it's that the majority of patients do appear to recover and that the death rate is actually lower than what we see with epidemic influenza, about 3.5 percent of the patients have died from the illness. That is still a tragic occurrence for the people who are affected, and their families, and I would never mean to minimize it. But it is fortunate that it is not even more severe.

China's Policies Have Made The SARS Problem Far Worse

The real tragedy in the case of SARS is that the Chinese government has managed to make a bad situation worse. In spite of the fact that SARS first surfaced in China in November 2002 the rest of the world did not hear about it until it started causing infections in Hong Kong and Vietnam a few months later. The irresponsibility of the Chinese government may lead to a massive outbreak throughout the world.

The president of Taiwan, which has 10 cases of Severe Acute Respiratory Syndrome (SARS), has been the most outspoken. "SARS first broke out on the Chinese mainland, but the authorities covered up the information, leading to a global epidemic," Chen Shui-bian said on Friday. China initially admitted to five deaths, but a toll of 31, and 800 infections, since November was revealed on Wednesday.

The press in China is highly controlled and is not a reliable source of information about the extent of SARS in China. Also, the Chinese government has resisted providing the WHO much information about SARS. On Friday March 28 2003, over 5 months after SARS first showed up in China, the Chinese government finally agreed to allow WHO disease experts access to Chinese information about SARS infections in China. But it is far from certain that China will be completely forthcoming. One international health official quoted off-the-record in the article above says that the disease is probably far more widespread in China than the government of China is admitting to even now. There are parts of China that are poor where most of the population have little access to health care services. Even if the most developed countries take steps to slow the spread of SARS at this point it seems likely that SARS will spread in less developed countries.

If China had reported its SARS outbreak back in November of 2002 we'd be about 4 or 5 months further along in developing tests, developing vaccines, studying its mode of transmission, and developing ways to minimize its spread. But the Chinese government instead hushed it up and the result may eventually be millions of deaths that could have been avoided.

How To Avoid SARS?

What to do to avoid becoming infected? Face masks may not help that much.

Doctors say sick people who put on masks become less likely to transmit the illness when they cough or sneeze. But it is unclear whether the masks help the healthy. They quickly become saturated with moisture from breath and lose some usefulness when worn for hours - much less for days, as is happening here now - local doctors warn.

We really need to know more about the efficacy of facial masks for blocking SARS' spread. If it looks like SARS is going to spread into the general population keep in mind that protecting the eyes from airborne droplets might also be of some value for reducing risks. Goggles or safety glasses might reduce the risks of transmission. Also, frequent hand washing when out in public places may also reduce the risks of getting the illness.

One big question in my mind is about how duct work and air filters are laid out in large buildings. Do most buildings do a good job of filtering out particles from air that comes out of each dwelling or office before that air passes into other areas in the same building? Also, could air filters be rapidly placed into existing buildings to reduce the spread of airborne virus particles? If people begin to fear living and working in large buildings the economic costs of the fear of SARS could become enormous very quickly.

If SARS breaks out into the general population the fatality rate may rise. Currently because so few people have SARS each person can receive a great deal of care including respirators when necessary. But if large numbers of people become infected there will not be enough equipment or medical workers to care for them.

SARS may cause an enormous economic impact. If the fear of SARS grows large enough then many people will avoid both business and personal travel, restaurants, movie theaters, shopping malls, and other public places with large numbers of people. Consumer demand will therefore decline and the rate at which business deals are negotiated will slow.

Also see my previous posts on SARS: Severe Acute Respiratory Syndrome Causing Concerns and Hunt For Cause Of Severe Acute Respiratory Syndrome.

Update: If a coronavirus is causing SARS it could easily mutate into an even more lethal form.

But coronaviruses are prone to transformation. They have an unusually large amount of genetic material, as well as enzymes that enable them to shuffle it. A new, more virulent mutant could easily result.

As demonstrated by the quarantining of the passengers and crew of this American Airlines flight the economic costs of SARS could swiftly become immense.

American Airlines Flight 128 from Tokyo is being held on the tarmac at San Jose International Airport after two passengers and two crew members complained of feeling unwell, airport officials said.

People will become more afraid to fly if SARS continues to spread. Also, if many flights get quarantined there will even be a reduction in the number of flight crews available to fly aircraft.

Some airlines in the Southeast Asian region are moving to reduce the risk of infection. Thai Airways International and other airlines of Thailand are requiring passengers from high risk countries (Singapore, Hong Kong, China, Taiwan and Vietnam) to wear surgical masks.

Here's some more bad news about surgical masks. Australian expert David Bromwich says surgical masks do not provide much protection against airborne disease.

But David Bromwich, an expert in respiratory protection from Brisbane's Griffith University, said that passengers wearing surgical masks to guard against respiratory disease were "kidding themselves". Dr Bromwich said surgical masks were originally designed to stop transmission of saliva from doctor to patient, but offered almost no protection from tiny airborne disease particles. "It's a false sense of security," he said.

Since surgical masks do not provide much benefit I guess it doesn't matter that there is an enormous surgical face mask shortage developing. The 3M plant for manufacturing N95 surgical masks is operating at maximum capacity and can not keep up with demand.

The masks, made of a micro-fibre designed to filter out impurities, are manufactured at a plant in the United States, currently operating 24 hours a day under a "state of emergency."

Canada, which has been much harder hit by SARS than the US faces a surgical mask shortage for medical workers.

Hong Kong just reported a new single day record of 75 new cases of SARS diagnosed and other countries are reporting new cases. These cases are spurring countries in the region most hard hit by this new disease to take increasingly stringent measures to stop the spread of SARS.

Hong Kong invoked a colonial-era law Tuesday to quarantine more than 240 people in countryside vacation camps, part of redoubled efforts to halt the spread of a mysterious flu-like illness that has killed at least 63 people around the world.

The 240 are all from block E of the Amoy Garden apartment building complex.

Update II: SARS is still not as easily transmitted as influenza.

SARS has so far killed about 3 to 4 per cent of the 1500 sufferers. But be thankful it is not as infectious as common influenza.

"If it were flu, it would be all over the world with millions of people infected," says Victoria's public health chief, Dr Robert Hall.

The containment of SARS has been found to be quite difficult for public health authorities and success is by no means assured. There is a lesson here: If a more easily transmittable disease of equal or greater lethality emerged then unless the threat it posed was recognized at a very early stage and attempts to stop its spread were very aggressive it is unlikely that it could be contained.

By Randall Parker    2003 April 01 01:43 AM   Entry Permalink | Comments (2)
2003 March 19 Wednesday
Hunt For Cause Of Severe Acute Respiratory Syndrome

The Scientist web site has a good article on the hunt for the cause of SARS. The web site requires registration to access its articles but the registration is free and the site has generally good quality articles. Donald Lowe, head of the Department of Microbiology at Mount Sinai Hospital in Toronto thinks the hunt for the cause will succeed rather more quickly than similar hunts in the past.

But it took six months to identify the Legionella pneumophila bacterium as the cause of Legionnaire's disease, the pneumonia that attacked an old soldiers' convention in Philadelphia in 1976. Could it take just as long to identify the cause of SARS?

Unlikely, Lowe thinks. "Since Legionella, the molecular world has changed dramatically — if we have any evidence of an infectious particle, we can amplify the DNA or RNA, sequence it, and therefore be able more rapidly and accurately to define an agent. Unless we are dealing with a virus which is difficult to grow."

The New Scientist reports that a Canadian lab has ruled out 250 types of pathogens by testing samples from Canadian SARS victims.

Suspicions are continuing to focus on a paramyxovirus.

Teams in Hong Kong and Germany said they had found evidence of a virus known as a paramyxovirus in at least some of the patients with the illness, called severe acute respiratory syndrome.

They stressed that more tests are needed before the virus is pinned down as the culprit, but said it is the best clue yet about the cause of the syndrome, which may have killed as many as 14 people and sickened hundreds more.

One of the Hong Kong scientists involved in the search for the pathogen is confident that his group has isolated the virus and that it looks like a paramyxovirus.

"We've identified the virus," said Dr. John Tam, a microbiologist at the Chinese University of Hong Kong, at a news conference late Tuesday. "We used an electronic microscope and found the virus in patient samples."

A similar virus found previously in Holland was slow moving.

John Oxford, professor of Virology at Queen Mary's School of Medicine, said a similar virus had been discovered in Holland last year.

"It is rather slow-moving, rather restricted to families and hospitals, not a rip-roaring affair, but still very nasty.

The World Health Organization says the presence of a paramyxovirus in SARS victims might just be a coincidence.

Viruses in the Paramyxoviridae family include many common, well-known agents associated with respiratory infections, such as respiratory syncytial virus, and childhood illnesses, including the viruses that cause mumps and measles. Some of these viruses are widespread, particularly during the winter season. Screening of specimens could therefore be expected to detect particles of these common viruses. At this point, it cannot be ruled out entirely that tests for the SARS agent are detecting such “background” viruses rather than the true causative agent.

The Paramyxoviridae family also includes two recently recognized pathogens, Hendra virus and Nipah virus. These related viruses are unusual in the family in that they can infect and cause potentially fatal disease in a number of animal hosts, including humans. Most other viruses in the family tend to infect a single animal species only.

Nipah virus first began to cause deaths in humans in Peninsular Malaysia in 1998 in persons in close contact with pigs. The outbreak caused 265 cases of human encephalitis, including 105 deaths. Two separate outbreaks of Hendra virus, associated with severe respiratory disease in horses, caused two human deaths in Australia in 1994 and 1995. No human-to-human transmission was documented in either outbreak. No treatment was available for cases caused by either of these two viruses. Human-to-human transmission did not occur.

Even if the virus seen by the Hong Kong and German scientists via electron microscope is the infectious agent causing this disease and is from the paramyxoviridae family of viruses it is probably a previously unknown pathogen and not one of the known existing members of the paramyxoviridae family.

Still, Dr. Klaus Stöhr, a virologist and epidemiologist who is leading the health organization's scientific team investigating the illness, said that none of those viruses had caused a disease like the one under investigation, which doctors are calling severe acute respiratory syndrome, or SARS. Instead, the findings suggest that the virus might be a hitherto unknown member of the paramyxoviridae family.

If the SARS illness is positively identified as being caused by the paramyxovirus which the Hong Kong and German researchers have isolated then the only existing antiviral drug that might work against it is Ribavirin. Anti-viral drug development historically has been much more difficult than anti-microbial drug development. To date vaccines have been far more effective than anti-virals and this is likely to continue to be the case (though HIV is an exception to this pattern since HIV vaccine development has proven so hard to do). Other viruses of the paramyxoviridae family include measles and mumps and of course vaccines do exist for them. It therefore seems reasonable to expect that if the SARS illness is being caused by paramyxovirus the development of a vaccine should be possible.

Drug development time and vaccine development time are both usually measured in years. An exception to this is influenza. For influenza every year vaccines for new strains are usually developed within months of when the new strains are first detected. However, if this SARS pathogen is a paramyxovirus it is probably a species unknown to scientists and perhaps even from a genus heretofore unknown. Therefore developing a vaccine for it will require a lot more work to first understand it to a level of detail that would make vaccine development possible.

In the short to medium term the best line of defense against the SARS pathogen is likely to remain the rapid isolation of its victims. But the work to isolate and identify the virus is important because it will lead to tests for its presence. The ability to test and detect it will lead to a much more rapid ability to identify and isolate those who are infected by the virus. That, in turn, will help to prevent its spread. Therefore the race going on to identify and characterize the SARS pathogen could lead to a fairly rapid benefit for the public health.

The CDC has a web page where all CDC SARS press releases are published. The World Health Organization puts out all the WHO SARS press releases on their general press release page.

Update: The SARS illness spread from China. It started there in November 2002. The Chinese government was very irresponsible for not telling the rest of the world about the illness until after it had spread to outside of China.

Although the outbreak in Guangdong province started in November, health officials said almost nothing publicly for months afterward. Chinese officials gave their first report of the outbreak in Guangdong province to the World Health Organization on Sunday, saying that the outbreak was abating on its own. The report raised hopes at the World Health Organization that it would burn itself out elsewhere as well.

Because millions of poor Chinese people live in close proximity with chickens and pigs new strains of influenza sometimes jump across from other species into humans. These strains have a much greater potential to be very virulent in humans than the strains that emerge from within the human population. Therefore China is the most probable origin of an influenza whose lethality could rival the so-called Spanish flu of the 1918 pandemic. For China to be slow about notifying the rest of the world about a newly emerging illness is therefore an extremely dangerous practice. Governments and public health officials around the world should be sharply critical of China's lapse in its responsibility in this matter.

Update II: For more on SARS see Charles Murtaugh's post on SARS and my previous post on SARS.

Update III: The extent of the Chinese government's irresponsibility in failing to inform the rest of the world of the emergence of the SARS disease before it escaped from Guangdong province China is brought into sharp relief by the revelation of how SARS disease crossed over into Hong Kong. The carrier is now believed to have been a Guangdong doctor aged 64 who stayed in a Hong Kong hotel and infected 6 other people staying on the same floor of the hotel.

Director Margaret Chan said the source of the outbreak appeared to be a Guangzhou doctor who stayed at the Metropole Hotel in Waterloo Road last month and infected six others.

Had the Hong Kong medical establishment been properly informed of the threat it is very likely that hospitals would have been operating with a far higher degree of caution when examining new admittees and those who became ill with this disease would have been diagnosed and isolated much more rapidly. The Chinese government deserves a serious loud dose of criticism for its handling of this matter.

Update IV: SARS is now suspected of being caused by a coronavirus. Blood serum from recovered victims has had gamma globulin extracted from it and injected into the bodies of those with very severe SARS and the gamma globulin treatments have been very effective in treating severe cases of SARS.

"Facts have proven that in at least 20 of our patients who went through very smooth recovery, their serum has been used to treat very severe sufferers and that has been very successful," said Leung Ping-chung, a professor and surgeon at the Prince of Wales Hospital in Hong Kong, considered ground zero of the outbreak.

Also see my more recent post Fears Grow That SARS May Spread Into Pandemic.

By Randall Parker    2003 March 19 10:26 PM   Entry Permalink | Comments (6)
2003 March 15 Saturday
Severe Acute Respiratory Syndrome Causing Concerns

Update VII: SARS now looks to be much more infectious than previously thought. See my later post Fears Grow That SARS May Spread Into Pandemic. Also read below for historical context about previous epidemics.

There is a new deadly strain of some kind of pathogen (its not yet clear if its an influenza but it is suspected to be a virus of some kind) has been making some people sick and it appears to have originated in Guangdong province China. The illness is being called atypical pneumonia or Severe Acute Respiratory Syndrome (SARS). The nature of the illness has started to raise alarms.

Before we get to that lets put it in perspective by taking a brief look at most famous and deadly influenza outbreak recorded in modern history. The lethality of that outbreak explains why public health officials become very worried when new strains of pathogens with increased lethality are reported.

During World War I a virulent influenza known as Spanish flu swept the world and killed tens of millions.

The Epidemic spread quickly around the earth. In all, some 525 million people were infected by the virus, with about 21 million people dying. That was more than twice the number who had been killed during the Great War. In many countries public gatherings were forbidden. The Flu was especially devastating on many people as they welcomed back their men from the war, overjoyed that they had managed to survive the slaughter that was the war. But their joy soon turned to grief when they found out that their men had brought the virus back with them, and it would not only kill them but also other family members.

The flu may really have originated in Tibet but the first known concentration of deaths from it occurred in Spain and hence its called the Spanish Flu. The estimates of how many died from it vary from 20 to 40 million. Spanish Flu struck down people in the prime of life.

Spanish Influenza swept the entire globe in the years 1918-1920, leaving a billion people sick, more than half of the worid's population at that time. It killed at least 30 million people, threc times the death toll of World War l (Wilton 1993). A study for Norway has recently resulted in an upward revision of the death toll. The suggested estimate is 14 676, twice as high as the most frequently cited figure (Mamelund 199Sa). The socio-economic impact of the flu was also considerable. One reason for this is that the flu took its greatest toll among people in their most productive ages (20-40 years, especially men), i.e. that part of life when people tend to marry and have children (Mamelund 1998a).

Spanish Flu killed far more than World War I.

The 1918 Spanish flu was one of the most contagious viruses ever known. It killed as many as 40 million people in the winter of 1918 and 1919, more than died in the First World War.

Flu strains vary considerably in their lethality. Spanish flu belongs to the Type A strain. Type A strains are usually more lethal than other types. See here and here for information about influenza types and how they mutate to form new strains. A later type A influenza strain killed hundrends of thousands in 1968:

Hong Kong Flu - Common name for the influenza A strain that killed nearly 750,000 people around the world in the 1968 pandemic

Influenza mutates. Some mutations are more lethal than others. As Spanish flu demonstrated, some can be incredibly lethal. Should we be worried that a new influenza strain might pop up and kill millions including members of our families and circles of friends? Well, on one hand we have more advanced medical technologies. You might think we could much better handle a new strain that was as harmful as the Spanish flu. But keep in mind that if a significant portion of the population gets sick all the hospital beds will fill up and there won't be enough respiratories and other modern medical equipment to go around. Also, we don't have highly effective treatments to use against viruses that compare to the antibiotic drugs that are effective for use against most bacteria (though the rise of drug resistant bacterial strains is making bacterial infections a growing concern).

Another problem we have is that cars and airplanes move more people around the globe and much faster than was the case over 80 years ago. So new disease strains can spread rather rapidly and can reach even remote places.

Still, its not all doom and gloom. The best way to avoid dying or getting very sick from a disease is to avoid exposure in the first place. The biggest advantage we have are far better ways to isolate ourselves from sick people. For instance, we live in less dense housing. Accounts of the 1918 epidemic describe immigrant families living in crowded New York City tenements where lots of people breathed each other's air. Individual families just had to have one member come home with the disease and soon ten or twenty others were all exposed to it and likely other people walking up and down the same staircases were exposed as well. By contrast, today we have smaller families and on average a much lower number of people living in each dwellling and more square feet of living space per person.

If it was suspected that some deadly disease on the order of the 1918 flu epidemic was on the scene then the most rational response would be to quickly and calmly reorder society in ways that would reduce risks of exposure. With this in mind one of the strangest (at least to my American eyes) things I saw riding subways and trains in Japan were people wearing surgical masks. Either they were sick and didn't want to pass their illness on to others or they wanted to avoid breathing in particles of influenza and cold viruses coughed into the air by others. Such a practice is easy to adopt. The inconvenience would be fairly minor and it beats dying. Even if there was a shortage of surgical masks all matter of cloth can be adapted to that purpose.

A reduction of exposure between humans can be accomplished in many other ways. People who go shopping can go less often, buy more per trip, and not go during rush hours when the isles are crowded. Optional activities such as vacations, club meetings, movie outings, concert attendance, and the like can be cancelled. People who are able to work from home can stop going into the office. Another simple thing is to avoid touching surfaces in public places. If you do then wash your hands quickly (perhaps with a bottle of antiseptic fluid). Better yet, wear gloves and avoid touching surfaces in public places. Also, when out in public avoid touching your face with your hands unless you've recently washed your hands. Even the people who can not change their daily routine will be at less risk if all those who can change their daily routine do so to the extent that they can.

Okay, so lethal epidemics can still happen. But we have lots of things we can do to reduce our risks of getting seriously ill or killed in such an epidemic. With all this in mind lets look at a recent development that has health officials thinking some pretty worried thoughts.

WHO issues a global alert about cases of atypical pneumonia

12 March 2003 | GENEVA -- Since mid February, WHO has been actively working to confirm reports of outbreaks of a severe form of pneumonia in Viet Nam, Hong Kong Special Administrative Region (SAR), China, and Guangdong province in China.

In Viet Nam the outbreak began with a single initial case who was hospitalized for treatment of severe, acute respiratory syndrome of unknown origin. He felt unwell during his journey and fell ill shortly after arrival in Hanoi from Shanghai and Hong Kong SAR, China. Following his admission to the hospital, approximately 20 hospital staff became sick with similar symptoms.

The signs and symptoms of the disease in Hanoi include initial flu-like illness (rapid onset of high fever followed by muscle aches, headache and sore throat). These are the most common symptoms. Early laboratory findings may include thrombocytopenia (low platelet count) and leucopenia (low white blood cell count). In some, but not all cases, this is followed by bilateral pneumonia, in some cases progressing to acute respiratory distress requiring assisted breathing on a respirator. Some patients are recovering but some patients remain critically ill.

Today, the Department of Health Hong Kong SAR has reported on an outbreak of respiratory illness in one of its public hospitals. As of midnight 11 March, 50 health care workers had been screened and 23 of them were found to have febrile illness. They were admitted to the hospital for observation as a precautionary measure. In this group, eight have developed early chest x-ray signs of pneumonia. Their conditions are stable. Three other health care workers self-presented to hospitals with febrile illness and two of them have chest x-ray signs of pneumonia.

World Health Organization issues emergency travel advisory

15 March 2003 | GENEVA -- During the past week, WHO has received reports of more than 150 new suspected cases of Severe Acute Respiratory Syndrome (SARS), an atypical pneumonia for which cause has not yet been determined. Reports to date have been received from Canada, China, Hong Kong Special Administrative Region of China, Indonesia, Philippines, Singapore, Thailand, and Viet Nam. Early today, an ill passenger and companions who travelled from New York, United States, and who landed in Frankfurt, Germany were removed from their flight and taken to hospital isolation.

Due to the spread of SARS to several countries in a short period of time, the World Health Organization today has issued emergency guidance for travellers and airlines.

“This syndrome, SARS, is now a worldwide health threat,” said Dr. Gro Harlem Brundtland, Director General of the World Health Organization. “The world needs to work together to find its cause, cure the sick, and stop its spread.”

There is presently no recommendation for people to restrict travel to any destination. However in response to enquiries from governments, airlines, physicians and travellers, WHO is now offering guidance for travellers, airline crew and airlines. The exact nature of the infection is still under investigation and this guidance is based on the early information available to WHO.

Countries are starting to discourage their citizens from travelling to areas where SARS has been reported. Thailand joins Singapore and Taiwan in urging their citizens not to go to Hanoi or southern China.

Passengers are being required to fill out health forms indicating whether they had been to the affected areas, and airlines have been instructed to report immediately if any passengers begin exhibiting symptoms.

The announcement follows similar moves by Singapore and Taiwan, which have both urged their citizens not to travel to Hanoi in Vietnam or southern China "unless absolutely necessary".

The experts do not know the type of disease causing SARS.

"It is either a new germ which hasn't caused a disease before or is a more common germ which has undergone a large change," David Bell, a public health physician at the Manila-based WHO Western Pacific office, said.

"If it is a new organism -- which has undergone significant change -- it may be more difficult to identify," warned Rob Condon, a WHO epidemiologist at the same office.

World Health Organization official David Heymann is clearly worried.

"It is not a very good situation," said Dr. David L. Heymann, a top expert in communicable diseases at the health agency. "It is a very difficult disease to figure out, and this has been going on for the last 10 days to two weeks."

Influenza has not been ruled out as the cause.

Among the survivors, "no one has gotten well yet," Dr. Heymann said in an interview. "It is not clear what is going on, and it is not clear what the extent of spread will be," particularly because "these are areas where there is a lot of international travel," he added.

The WHO spokesman sounds rather concerned.

Dick Thompson, a WHO spokesman in Geneva, could recall no such emergency travel advisory being issued in recent memory.

"Until we can get a grip on it, I don't see how it will slow down," said Thompson. "People are not responding to antibiotics and antivirals, it's a highly contagious disease and it's moving around by jet. It's bad."

Now that so many health authorities and medical doctors are attempting to identify victims of this disease it may be possible to contain it. One advantage we have today that didn't exist over 80 years ago is that information travels even more quickly than people do. A lot of the initial victims were hospital workers. One would expect the rate of infection of health care workers to drop as they recognize the disorder more quickly and take more drastic measures to avoid exposure from infected patients. However, one concern there is that in less developed countries the health care workers may lack the kinds of facilities and supplies needed to reduce their own degree of risk. Therefore the health care workers in less developed countries may end up either spreading the disease or they may turn away the sick and therefore the sick may not be properly isolated. Whether efforts at containment will work remains to be seen.

Will this disease spread and kill massive numbers of people? Don't know. Its certainly a story to watch very carefully.

Update: Encouraging news about SARS comes from a CDC press conference. Dr. Julie Gerberding of the CDC says the pattern of transmission so far has been through close personal contact.

QUESTION: And also, do we know how contagious? I mean if I was on a subway car with someone who was ill, could I get it from them, or do you need to have that close like I'm-taking-care-of-me kind of contact.

DR. GERBERDING: What we know so far from the investigations in progress are that it's very close personal contact of the type defined by WHO as having cared for, having lived with, or having had direct contact with respiratory secretions and body fluids of a person with the diagnosis. So there is no evidence to suggest that this can be spread through breath contact or through assemblages of large people; it really seems to require a fairly direct and sustained contact with a symptomatic individual.

If pattern of transmission continues then the chances of containing the disease will be much better. If it becomes as easy to transmit as a cold or regular influenza then containment would be much more difficult and perhaps impossible. So far there has been no indication whether the disease is transmissible during the asymptomatic incubation period. Whether it is will also affect the ability to slow or stop its spread.

Update II: Even if SARS doesn't turn out to be a massive killer plague (and its pattern of transmission suggests it will not be) we are still vulnerable to being killed off by a pathogen that hops into the human population from another species and that mutates into a virulent form. We have had close calls that have been contained such as the 1997 chicken influenza that was extremely deadly in humans.

In 1997 epidemiologists and public health officials from around the world got their first glimpse¹ of an entirely new variety of human influenza. Known as subtype H5N1 for the surface proteins which the virus carries, the new strain had only ever previously been observed in birds. Ominously, the effect of H5N1 on poultry had earned it the evocative title of "Chicken Ebola." And when it surfaced in the human population of Hong Kong last year it proved to be almost as deadly.

How deadly? Even with the advantages of intensive-care treatment, fully one third of the first 18 confirmed cases never recovered. They died.

Some additional accounts of the 1918 Spanish Flu Pandemic here and here provide a sense of how rapidly it spread and how difficult it would be to fight a similar outbreak today.

What is needed is the ability to develop and produce vaccines more rapidly. DNA vaccines are held out by some researchers as promising faster and lower cost manufacture with fewer side effects than many conventional vaccines. However, another promising approach is to use bacterial viruses knows as bacteriophages to produce vaccines very rapidly and cheaply.

BALTIMORE – March 10, 2003 – Genetically altered bacterial viruses appear to be more effective than naked DNA in eliciting an immune response and could be a new strategy for a next generation of vaccines that are easy to produce and store, say researchers from Moredun Research Institute in the United Kingdom.

"In theory, millions of doses can be grown within a matter of days using simple equipment, media and procedures," says John March, one of lead researchers presenting findings at the American Society for Microbiology's Biodefense Research Meeting.

Bacteriophages are viruses that infect bacteria but not humans. In this particular study, March and his colleagues used a bacteriophage as a vehicle for genes from hepatitis B virus in mice and compared its ability to elicit a protective immune response with a vaccine made of naked DNA. They found that not only could the bacteriophage induce an immune response, the number of bacteriophage they needed was less than 1 percent of the number of pieces of naked DNA required to mount an effective immune response.

Using bacteriophages to deliver vaccine components offers several advantages over vaccination with naked DNA, says March. The DNA is protected inside the protein shell of the virus making it longer lasting and easier to store. In addition, bacteriophages have a large cloning capacity, making large-scale production cheap, easy and extremely rapid – important attributes considering the current bioterrorism threat when sudden demands may be placed on vaccine stocks.

In order to produce vaccines the vaccines first must be developed. One has to have a design for a vaccine. Therefore the other needed element of a fast response strategy for new strains of influenza and even for new kinds of pathogens is to have high isolation labs that are equipped to rapidly take apart a pathogen and to develop vaccines for it. See my recent post United States Lacks Sufficient Biodefense Lab Space. What is needed is not just ultra-secure and ultra-isolated lab space. The labs would need to be equipped with or be located near labs that capabilities to do DNA sequencing, protein sequencing, protein structure determination and other relevant capabilities. Properly designed and equipped such labs could work on longer term problems between crises but when a deadly naturally occurring or man-made pathogen threatened to cause massive numbers of fatalities the best microbiologists and virologists could staff them and work to develop vaccines and drugs.

Update III: The illness may be caused by a paramyxovirus.

There is a long list of other candidates, with a family of microbes called the paramyxoviruses "certainly ranking on the top of most people's thoughts," said Klaus Stohr, a WHO virologist and epidemiologist who is helping to direct the investigation.

Update IV: The CDC has a web page where all CDC SARS press releases are published. The WHO puts out all the WHO SARS press releases on their general press release page.

Update V: To reiterate for those who are worried that SARS could become an enormous killer: It is spreading slowly. It appears to require fairly close contact to catch it. It does not appear to be as easily transmitted as many cold and influenza viruses. In a March 17, 2003 press conference Dr. Julie Gerberding, Director of the Centers for Disease Control and Prevention, says SARS is not being transmitted by casual contact. (bold emphases mine)

We know that the disease is so far limited to people who have had very close contact with cases. Most of the individuals are health care personnel who have been in direct contact with either the patient or body fluids from the patient. We also know that household contacts are at risk, particularly if they've had direct and sustained contact with sick individuals.

So far the cases are limited, as Secretary Thompson said, to individuals who have either lived in parts of Asia that are affected, or who have recently traveled from those areas.

We believe the incubation period is approximately 2 to 7 days, although as new information unfolds, that may be updated. So the travel advisories that have been issued stipulate that individuals returning from those areas with fever and respiratory symptoms within 7 days of their departure should seek medical attention to be sure that they are not in the early stages of this syndrome.

We also know that there is no evidence so far that persons not in direct contact with suspect cases are at risk. We have not identified any people with casual contact or indirect contact. I think we were reassured by the investigation here in Georgia, where there was an individual who acquired this infection presumably from family members, was here in this city while sick, was involved in activities that involved exposure to others in a workplace setting, and there is no evidence of spread from that kind of contact in the workplace.

Nevertheless, I stress again this is an ongoing investigation. We certainly don't have all the information we need to know to have certainty about any of these issues, and we will just simply have to update you as we go forward.

The most important thing that we need to do is to prevent spread of this infection, and I'll tell you some of the things we're doing about that right now. But the second most important thing is to figure out what's causing. This appears to be a contagious infectious disease, and as I said, limited to health care personnel and close household contacts. That suggests spread by the droplet route, and that's why our infection control precautions emphasize prevention of droplet spread through the use of face shields and gowns and gloves.

Update VI: The disease is increasingly looking like it is not spreading. Victims are popping up in more countries but the vast bulk of them all were infected in China or Vietnam. Therefore a general outbreak all around the world is looking less likely. Now that the knowledge about its symptoms has been widely disseminated victims are rapidly isolated and health care workers protected from exposure. Hopefully this trend will continue and the disease will be contained. The disease increasingly looks like a new pathogen

"As time goes by that is increasingly likely, simply because so many people have run so many tests," said Iain Simpson, a spokesman for the World Health Organisation (WHO).

"If it is something we already knew about we would almost certainly have identified it," he told Reuters.

While this disease looks like it is going to be successfully contained it should serve as a wake-up call that we are ill-equipped to deal with a deadly disease that spreads easily and that does break out into the general population. Some day a much more deadly influenza strain will cross over from fowl or swine into humans and as of yet we are unprepared to effectively deal with that eventuality.

Update VII: SARS now looks to be much more infectious than previously thought. See my later post Fears Grow That SARS May Spread Into Pandemic.

By Randall Parker    2003 March 15 05:45 PM   Entry Permalink | Comments (19)
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