Learning and not learning from SARS

The identification of the specific mammalian reservoirs for Sars is still a controversial subject. There is evidence rats were among the reservoirs.
The exact same problem applies to H5N1. The 19 bird sequences from birds in Indonesia were made public today at Los Alamos give further evidence a reservoir for human H5N1 other than domestic poultry exists. Please see www.recombinomics.com.
Just as Sars suddenly exploded, there is another time bomb that may soon explode, and the medical infrastructure in the US is not ready. The disease is XDR-TB, Extreme Drug Resistant TB, defined as strains which are resistant to all the current front line drugs and 3 or more of the 6 classes of second line drugs. This TB strain is virtually incurable. Four to six drugs must be taken at the same time, and these drugs are toxic, and reduce the lifespan of the patient. There are 340 known cases worldwide, and health experts say time is running out. It costs 100,000 pounds in England to treat one of these patients. In Victorian England TB caused 1 out of 4 deaths.
The name of the bacteria is mycobacterium tuberculis, and it exists worldwide. It has been seen in the US, Eastern Europe, England, and Africa. 1.7 million people die per year of TB. There is presently a explosion of this disease in Kwa Zulu Natal in South Africa, where 28 hospitals have identified patients with the disease. This disease could become a pandemic. One patient can infect at least 15 others, and hospital workers in South Africa are infected.
It is extremely contagious. All someone has to do is cough.
And many sick with the disease do not know they have it, and are out in society spreading it. South Africa has forced newspapers to stop publishing information on the disease.
It kills HIV patients rapidly, and could spread into the general population. If it attacks patients sick with H5N1, it would probably kill them.

Niman might be tap-dancing here. It appears the latest Indonesian avian isolates do match at least some human Indonesian isolates, although they are geographically dispersed. I'm not a virologist so I won't comment further.
Would be interested in comments by those who do have the background.

A little off the subject, but not completely. SARS had a fairly long incubation period, while influenza typically doesn't. I have the impression that there is disagreement between models of the effectiveness of isolation/quarantine for influenza as opposed to SARS.

Is public health pursuing a viable containment strategy with isolation/quarantine for influenza? Or are we preparing to practice defensive public health. Since, I don't like dilemmas; I'll also offer the choice of both.

william: MDR TB has been around for a while. I will post on this eventually, but you are mixing all sorts of problems together. When I was born all TB was "drug resistant" because there were no drugs. If you are immune suppressed you have a special problem, but otherwise I don't think this version of TB is different than the TB that was around in my youth (and which infected me asymptomatically). In my day, virtually all health care workers converted to positive skin tests by the time they finished training. The vast majority of people infected with TB do not have clinical symptoms.

Regarding non poultry reservoirs of H5N1, we have posted on this quite a bit. What more are you saying -- and more importantly, why? The hysterical quality of your posting and its volume and frequency obscure lots of points. You need to think things through, not just impulsively throw up a rant. I told you this when you posted as Juan on the other site.

Doug: First it is important to distinguish isolation (segregation of the sick) from quarantine (segregation of those exposed but not sick or those you think might have been exposed). Quarantine won't work for influenza and would probably be counterproductive. Most reasonable people think isolation would be well accepted and makes sense.

SARS and flu have very different epidemiology. There is debate whether quarantine made and difference for SARS or in fact whether anything made any difference, but it is at least plausible that for the reasons you suggest things would work very differently since people were usually not infective before they got symptoms, unlike flu.

As for public health being defensive, in the absence of a vaccine or sufficient and reliable and logistically feasible drug prophylaxis, consequence management is our only option. It is not purely defensive in that building a robust public health and social services infrastructure to be resilient in the event of a pandemic has many side benefits for other things.

Thank you for your comments. My comments were related to physicians practicing defensive medicine. I was just cinsidering if we in public health do similar things for similar reasons.

Our plans anticipate that both isolation and quarantine will fail at some point in the epidemic. So do I elevate risk for an already limited staff in order to implement a strategy that may not work, and will certainly fail? Perhaps to the point of losing capacity to administer vaccine when it does arrive? Or should our staff hunker down to conserve capacity, and pop back up when we can implement a proven strategy? This is why I am considering giving up ethics altogether.

Doug: I'm surprised you have quarantine plans at all. Who are you going to quarantine? How will you enforce it? What is the evidence it will do any good? Isolation, on the other hand, will probably happen by itself as people too sick don't move around that much and there will be a lot of pressure for them to stay home. Isolation is an easy sell. Quarantine a hard one, won't work, will cause loss of credibility and trust and will be counterproductive (people fleeing the area and spreading it further, unequal application with the well off not subject to it, just the poor, etc.).

Revere,
No joke. I work at the local level now, and if we want the planning funds from CDC through our state, we have to hit certain planning targets, including plans for isolation and quarantine. We need the money, so I have the plans. Prostitution isn't so bad once you get used to it.

Revere: "...it is at least plausible that for the reasons you suggest things would work very differently since people were usually not infective before they got symptoms, unlike flu."

Am I right your summary or conclusion here makes a world of difference between the SARS outbreak and a H2H H5N1 outbreak when the latter becomes more ready transmissible?
The incubation time would be of little importance in SARS because only when symptoms are becoming visible one is potent of infecting others? While H5N1, as we suspect, is infecting others while symptoms are not visible yet, and so any incubation time poses a big risk, not only to the patient who probably will not take any antiviral but also to others in his/her close environment?
This could be one factor in the sudden halt of SARS after those numerous outbreaks (correct me if I am wrong), because SARS was containable after tracing most (if not all) patients by their syptoms at last. Like smallpox (where they could even trace infection from bedlinen in some cases). Whereas H5N1 will not be containable because it can easily spread while it's still invisible, airborne and rapidly replicating. (But it's not doing yet so much at this time.)??

I agree completely with you we should take the opportunity given to us to set up an international standardized minimum data set for H5N1 patients.
But shouldn't there also be done some new laboratory experiments from now on, on SARS in vitro and although I don't like it, also on animals to get some differential effects in order to make more sense out of the described treatments given to SARS patients at that time?
For I read a more positive treatment outcome tendency is to be found from treatment agents in the In Vitro studies, while real patients are experiencing more iatrogenic damage than implicated from in vitro studies. This certainly will have important consequences nowadays to other infectious diseases (the operation was a succes, the patient died) and Big Pharma. For instance, I learned medicine studies on what's suitable for children often are not published when the outcome is unfavourable.
As live (in vivo animal) experiments could not be done during the SARS outbreak maybe these can be done afterwards, if someone is interested enough to invest in it.

something in general but not specifically about SARS:
http://www.ezinearticles.com/?The-Operation-Was-a-Success--The-Patient-…

Reveres, I am confused about the "cytokine storm". Suppose a person is prepping, and as part of that prepping they are trying to bring their immune system up to optimum by good diet, vitamin and mineral supplements, exercise, etc. (which anyone should be doing anyway?). Suppose that person becomes ill with bird flu. Are they MORE or LESS likely to suffer a cytokine storm because of their "boosted" immune system?
Thank you for considering my question.
Library Lady

LL: You are not the only one confused by cytokine storm. This is just a shorthand way to designate a dysregulated signalling system that leads (in this case) the signals to send inflammatory cells to the lung to be stuck in the "on" position.

We don't know what causes this to happen. It might be the virus itself that does this or some consequence of the infection. In my view, getting your immune system "ready" won't affect that at all. The better your immune system works the better off you will be since it is your immune system, in its various parts that is your primary protection. For some reason it can also operate terribly wrongly, just as a car can go out of control when its accelerator is stuck down. But that's not an argument for not keeping your car well maintained and in top operating condition.

SARS was to some degree prevented from becoming a global pandemic due to the fact that fairly early in the outbreak airlines in affected regions began checking passengers both as they boarded and as they disembarked. Those showing any signs of illness had their temperatures checked on the spot, as I recall, and if they were running a fever they were quarantined until tests for the SARS virus could be run. I read somewhere recently that some airlines - I believe it was in China - are planning to install devices that measure the temperatures of all people as they go through check in (probably similar to a metal detector, but for body temp) in a similar effort to curtail the spread of bird flu: However if, as you say, carriers of H5N1 can be infective prior to becoming obviously ill - or as recent data from So Korea suggests, there may be more very mild or even asymptomatic cases of H5N1 than previously thought - these temperature measuring devices would probably do little to stop the global spread of the bird flu via air travel.

MiH: Don't have the cite to hand, but it was determined later that the airport measures (e.g., fever screening) had no effect. So we don't really know what happened to SARS. Bit of a puzzle. But we were damn lucky.

Revere wrote:
"We don't know what causes this to happen. It might be the virus itself that does this or some consequence of the infection. In my view, getting your immune system "ready" won't affect that at all."

I am beginning to study the components of Cytokinic Dysregulation and have found that, though, we don't conclusively know anything about it, we do have a substantial body of data available. In reviewing the data, I've found references to incompetent NF-kB potentially being an open door to early and rapid viral replication.

Some of my thoughts on this matter are counter-intuitive to others, I know.

Incompetent NF-kB, a substance found in your cytoplasm, may be implicated by its failure to translocate and/or to activate the necessary genes (dozens potentially) for viral clearance. If we are able to devise a method of causing the body to make fully functional NF-kB or to reform the incompetent NF-kB, then are we creating proper immune response by building the essential components of the immune system? True or not True?

I'm not asking anyone to try this at home. I'm inviting study on the matter. We are discussing these ideas on the FluWiki at http://www.fluwikie2.com/pmwiki.php?n=Forum.CytokinicDysregulation4 if you'd like to comment?

Immune boosting can have just as bad an effect as immune suppressing. Deep nourishment is very different from immune boosting or immune stimulating.

Please know that deeply nourishing the immune system is essential if we are to build these fully functional components. What are the odds that the average person gets all that's required to build these components?

MiH -

If what I read about SARS is correct, and my memory in working order (which is a really open question some times), SARS patients didn't become infectious until much later in the progress of the disease than influenza patients.

Influenza patients are contagious as much as a day or more before they have clinical symptoms, if I've not been misinformed. Influenza is a stealth infector. So airport screenings like those you describe would be pretty worthless in containing it.

Reveres -

I didn't know about the prevalance of asymptomatic TB.

When I was a kid in Tucson, the issue was using X-rays to screen. Those would show false positives for prior TB quite often for long-term Tucson residents because of the prevalence of coccidomycosis, or "Valley Fever". Live long enough in urban Southern Arizona and you're liable to come down with it. And it's not always a mild infection.

It came VERY close to burying one of my grad school professors, and he was one of the fittest people in the whole department if not the whole campus. Running, exercise, volunteer Search and Rescue work, the whole nine yards.

It WILL bury dogs like boxers, with foreshortened muzzles.

NS1: NFκB is a transcription factor that can be activated by many different things (e.g., the many agonists of the Ah Receptor, like PAHs or dioxin). It is interconnected with many signalling pathways and its dynamics in the cell are very complicated and we know only some of it, little bits and pieces of the things that affect it. It is not surprising to see its levels change or affected in cytokine dysregulation because it turns on so many other genes. Manipulating NFκB would be very problematic and fraught with difficulty and danger, IMO.

Charles: The usual way to screen for TB then and now is the tuberculin skin test. You can also see TB (inactive and active) on x-rays, usually as apical scarring, and it was sometimes picked up that way on routine chest x-rays, although other things can do that as well.

Two or three days ago I sent Revere a picture of the people in the terminal at HCM City with masks on and taking temps... I asked the question then if there was something that we weren't hearing from the media. Indeed, we arent. From the notices to airmen they are checking temps there. You better hope you arent warm when they do because the skinny is that they basically quarantine you if there is a sustained temp over a six hour period. You are masked up the second you hit the ground from any other Asian city. So while prudent, its in response to something I would say.

So our Asian brothers in this world once again aint fessing up to something. We will probably hear about it in either a neighboring country newspaper or OIE report about a non existent massive killing of humans or animals...Then they'll deny it again.

Randy: Wearing surgical masks is a common practice in many Asian countries. You see people doing this on the street, the subway, buses, etc.

With regard to airport screening and SARS, Revere wrote: "it was determined later that the airport measures (e.g., fever screening) had no effect."

There are excellent published data showing that airport screening picked up few or no actual SARS patients.

But many experts also cite anecdotal data that the highly-publicized existence of airport screening stopped lots of sick people from even trying to fly -- sort of the way metal detectors stop most people from trying to bring guns on planes.

Public health experts know that "presentee-ism" -- the presence of sick employees who really ought to be absent -- plays a large role in transmission of respiratory diseases. Airport screening would almost certainly have kept Guangzhou Dr. Jiu Jianlun, from flying to Hong Kong in mid-February 2003. Dr. Liu started having flu-like symptoms and fever five days before that flight. In Hong Kong, he became the index global superspreader at the Metropole Hotel, infecting people who then flew off to Hanoi, Canada, Singapore, and elsewhere.

One of those who crossed paths with Dr. Liu's germs at the Metropole Hotel, American business man Johnny Chen, flew to Hanoi, where he checked into the French hospital, and infected dozens of medical staff and others, including WHO's Dr. Carlo Urbani who examined him in late February. I don't know if Chen had fever before he left Hong Kong.

Dr. Urbani did have symptoms before he left Hanoi on March 11 2003 and flew off to Bangkok. The director of the WHO Hanoi office, Pascale Brudon, said, "Just before catching his flight he called me and told me that he felt tired and that he might have some fever."

I believe there were some probable indirect benefits in reducing travel by undiagnosed SARS patients, who were thought to be infectious only after symptoms began. I have not seen any models which suggest that airport screening would stem the tide of an influenza pandemic, given the early transmissibility of influenza by asymptomatic patients.

Path Forward: There is something rather alarming and sadly predictable worth noting in your report above. People who were at the forefront of knowledge regarding SARS transmissability - Dr Liu and Dr Urbani, who absolutely knew better, as well as business man Johnny Chen - knew they knew they were in a SARS outbreak area, knew they had been exposed, knew they felt sick and potentially were carriers...yet none the less did not isolate themselves and rather boarded airplanes and spread the virus further. They apparently felt they were "too important", their business matters "too pressing" to be postponed. How many world travelers will feel the same way, especially those less educated, less certain of their exposure? How many will tell themselves "Oh, it's only an ordinary virus, a touch of the common flu or cold" as they board that jumbo jet to spread the H5N1 across the world? If we can't trust those who are the best informed to keep to common sense precautions, we certainly can't trust the average person.

MiH: If you haven't read Greenfeld's book on SARS its worth reading (China Syndrome). The people you mention had no idea they had SARS. The only one who might have had an inkling, Urbani, also was instrumental in saving many lives and he did not spread it.

You seem to be very anxious to affix blame but events didn't unfold in the way your hindsight suggests.

I have not read the China Syndrome yet...however, the facts being in a book don't necessarily make them right.

'Spin' can and has been packaged in a lot of innovative ways by desperate people.

Tom: The book is pretty good and my friends from Hong Kong say it is pretty accurate. There are some science errors in it but nothing that affects the main content. It is a scathing indictment of China. Greenfeld was the Times Asia editor and traveled in China and lived in Hong Kong during the outbreak. I recommend it.

I know they wear the masks Revere. It doesnt account for the thermometer stuff though.

Some comments on the cytokine storm. Though both SARS and H5N1 share it in common, recent research shows that the mechanisms are quite different. (I'll have to dig out the references.) There is still ongoing controversy about whether people with strong immune systems are worse off than older people whose immune system is less effective. Of note was that the 20-40 age group suffered the worse in the 1918 pandemic. However, I'm not so sure this was because they were the group that was the most immune healthy.

Several in-vitro virology studies point to the fact that within minutes of invading the nucleus, the components of H5N1 start dysregulating the cell's cytokine (signaling apparatus) by accelerating the pro-inflammatory cytokines, and inhibiting the anti-inflammatory cytokines. Many other entities can also do the same thing. We discussed here not so long ago the results of the TGN1412 monoclonal antibody experiment in healthy young males that went badly awry, that did the same thing (for unknown reasons0, so H5N1 is not unique in this respect.

NS1: NF-κB is normally sequestered in cytoplasm and inhibited by a family of inhibitory proteins, the IκBs, so that its nuclear localization signal is masked. However, a variety of cytokines, including IL1 and TNF-α, are believed to activate specific kinases and ubiquitin ligases that can ultimately lead to degradation of the IκBs, which permits translocation of NF-κB to the nucleus and further upregulation. As Revere says, this is a basic cellular mechanism.

Tom, I agree with Revere that the book pretty much details the epidemic as it happened. You have to remember that hindsight is 20/20; we knew damned little about SARS during the epidemic. In fact, as I recall, most virologists were shocked that a coronavirus could have such virulence. If it hadn't been for the work of Urbani and a few other epidemiologists, things could have been a lot worse. Urbani worked hard to uncover some evidence even though he was dying.

Revere Thanks.

Marissa. While I have great personal admiration for Dr. Urbani and other individuals...I have zero or less than zero admiration for the World Health Organization as an organization... the 'amorphous blob' that it is.

I live in the vicinity of Toronto, Ontario, Canda. I am well aware of the fact that SARS was and had been spreading out of emergency departments into hospitals and communities for ten days before the World Health Organization finally got around to announcing to the world that there even was a problem.

I am well aware that the World Health Organization was complicit with the Government of China for several months in the coverup. If this book describes the World Health Organizations perfomance as exemplary...then at the least a partial re-invention of history has occured for whatever reason.

Why is this important? Because the same players (Hi Dick) are doing the same thing now.

If the H5N1 coverups in China continue with the World Health Organizations being complicit again...

...then we will have the largest case of preventable genocide in the world's history and I hope every one of them ends up before the World Court.

If you don't learn from your mistakes you repeat them. Patting the World Health Organization on the back for a job well done with SARS is spin and benefits no one and blaming it on a flawed mandate is what it looks like...an excuse.

Making one of those who were complicit the new head of the complicit organization that has downplayed and covered up the threat of H5N1 for 9 years (remember Dick's quote 2-7 million worldwide mortality only - Jan 2005) doesn't help either.

Tom: Blanket condemnations of WHO because you don't like how they have done on H5N1 (neither do I) or SARS (I am agnostic or even slightly pro, after reading the details) seem to be throwing the baby out with the bathwater. This organization does a lot of good in the world. I know some very cruel veterinarians and neither Canada nor the US are at the top of my list of forces for good at the moment. But both do some very good things, and most vets care a lot about their patients. WHO has some big problems at a time when we need them most. They have shown they can also do a lot of good and right now there are no other resources. I don't count Gates, as they are private and the world's people have no control over what they might do, be it good or bad. So WHO remains the only game in town. I'd like to presssure them to do better, not simply zero them out (which would be a real tragedy for hundreds of millions of people).

Revere. If you are agnostic or slight pro after reading the details...then you have been spun...with all due respect of course. /:0)

I think we have appeased the incompetence etc. at the World Health Organization for long enough...and now we have painted ourselves into a corner...I am tired of their excuses...they should either do their job or get out of the way and let others do their job for them.

They are about to become complicit with the Chinese Government in the largest preventable genocide in the world's history...whether that genocide is created by nature or created by nature with a good deal of assistance by unnamed professionals.

Tom: I still suggest you read Greenfeld's book, which is no whitewash of WHO. Since this is a matter of great concern to you, I think you owe it to yourself. I can't change your mind about WHO, nor do I know if they will be a help or a hindrance in whatever will transpire in the near future. But if they "get out of the way" there is no one else standing there to take up the slack in their particular venue.

The battle against a pandemic will be fought locally, not by WHO and not by CDC or Health Canada. Meanwhile, though, WHO and CDC and Health Canada continue to do many things I am glad they are doing. I wish they would do them better and I think in the US if we had a better government they would do them better (same for Canada, BTW). WHO can do better with a decent DG, which they haven't had for a long time. Lee was terrible and Brundtland had other fish to fry. We need a good DG and some member states like the US who support WHO and the UN instead of trying to tear it down.

As you know, we are in agreement about the suitability of Dr. Chan for DG, so that's not at issue, here.

Revere.

I do believe you and I 'dance on the head of a pin'.

Thank you for giving me a voice in the matter...it is greatly appreciated!!

Revere wrote:
"NS1: NFκB is a transcription factor that can be activated by many different things (e.g., the many agonists of the Ah Receptor, like PAHs or dioxin). It is interconnected with many signalling pathways and its dynamics in the cell are very complicated and we know only some of it, little bits and pieces of the things that affect it. It is not surprising to see its levels change or affected in cytokine dysregulation because it turns on so many other genes. Manipulating NFκB would be very problematic and fraught with difficulty and danger, IMO."

Reveres and Marissa,

Thank you for reviewing my post here.

Please go deeper. Would you mind having a look at one or more of the papers that I've cited at FluWiki on the topic? I do believe that if you were to pursue this with us for even a short distance that you might begin to see a possibility.

I fully understand your concern over the complexity and the complicity or interconnectedness of these factors. I also know that if we don't look for some unifying theorem here, and quickly, we'll have no paddles as we rush down a raging torrent.

NF-kB seems to play a very foundational role, potentially close to the extreme beginning signal, for the innate immune response. I'm not asking for us to jump the gun and attempt to regulate NF-kB at this time. I'm still hoping to define from the present studies and extensive evidence where the failure begins in the body's response to HPAI H5N1.

I've laid broad groundwork for these basic questions at http://www.fluwikie2.com/pmwiki.php?n=Forum.CytokinicDysregulation4 including a detailed list of potential paths of pursuit.

In a matter this complicated, sometimes you have to choose one path and study it deeply. This path is most logical to me. We have an amazing body of evidence related to NF-kB. Let's put it to work!

Gather and Solve.

NS1: send me your e-mail address please. Mine: marrissajan@aol.com)

NS1: Oops. Should be marissajan@aol.com. Not enough coffee in the system yet!

Marissa: Done. Thanks. We look forward to the discussions.