Comments on: Lessons in History: what we can learn from… the Spanish flu http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/ now with extra source Sun, 12 Feb 2012 10:13:47 +0000 hourly 1 http://wordpress.org/?v=3.2.1 By: Ben Aveling http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-27198 Ben Aveling Sun, 24 May 2009 21:26:09 +0000 http://www.crikey.com.au/?p=58340#comment-27198 @Jackson, Mike I don't know if this has been an efficient way of discussing this, but it certainly has been interesting. Thank you both. @Jackson, Mike

I don’t know if this has been an efficient way of discussing this, but it certainly has been interesting. Thank you both.

]]> By: Jackson Harding http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26676 Jackson Harding Fri, 15 May 2009 09:01:47 +0000 http://www.crikey.com.au/?p=58340#comment-26676 Mike, Yes it does. The whole cytokine system is incredibly complex (there are many identified substances, and probably even more as yet unidentified) and they are responsible for modulating much of the immune response, fighting off the array of bugs were are assailed with every minute of every day and most critically modulating the response to serious incursions by nasty pathogens. In simple laymans terms with cytokine storm you see all manner of effects often unrelated to the primary site of infection, direct lung damage leading to pulmonary haemorrhage (which is where the blood was coming from with the 1918-19 flu if the descriptions of the reconstituted virus in other primates is any guide), kidney damage, direct cardiac effects including reduced pumping ability, leaking of body fluids from the vascular system into tissues causing swelling, increased ability of all the bugs that live in your bowel (and your body usually keeps at bay) getting into the circulation, and most critically a lack of oxygen getting into your blood via your lungs for several reasons, not least of which is your lungs filing up with fluid and possibly blood. The lack of oxygen causes other cells to become stressed and possibly even to die. One of the bodies responses to this insult is to release more cytokines, which can then make things worse. Back and forward here is probably not the most efficient way of doing this. I'll ask the editors to forward you my email and if you are interested we can discuss this elsewhere. Jackson Mike,
Yes it does. The whole cytokine system is incredibly complex (there are many identified substances, and probably even more as yet unidentified) and they are responsible for modulating much of the immune response, fighting off the array of bugs were are assailed with every minute of every day and most critically modulating the response to serious incursions by nasty pathogens. In simple laymans terms with cytokine storm you see all manner of effects often unrelated to the primary site of infection, direct lung damage leading to pulmonary haemorrhage (which is where the blood was coming from with the 1918-19 flu if the descriptions of the reconstituted virus in other primates is any guide), kidney damage, direct cardiac effects including reduced pumping ability, leaking of body fluids from the vascular system into tissues causing swelling, increased ability of all the bugs that live in your bowel (and your body usually keeps at bay) getting into the circulation, and most critically a lack of oxygen getting into your blood via your lungs for several reasons, not least of which is your lungs filing up with fluid and possibly blood. The lack of oxygen causes other cells to become stressed and possibly even to die. One of the bodies responses to this insult is to release more cytokines, which can then make things worse.

Back and forward here is probably not the most efficient way of doing this. I’ll ask the editors to forward you my email and if you are interested we can discuss this elsewhere.

Jackson

]]> By: Kerrie Gandara http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26640 Kerrie Gandara Fri, 15 May 2009 04:34:54 +0000 http://www.crikey.com.au/?p=58340#comment-26640 Very interesting article AND feedback comments, but now I'm not feeling very well! Very interesting article AND feedback comments, but now I’m not feeling very well!

]]> By: MIKESTUCHBERY http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26622 MIKESTUCHBERY Fri, 15 May 2009 01:19:50 +0000 http://www.crikey.com.au/?p=58340#comment-26622 So, aside from the 'the immune system eats you' description of a cytokine storm, what do you see in a patient in the midst of one of these immune reactions? Does this account for the arcing nosebleeds and vomiting? So, aside from the ‘the immune system eats you’ description of a cytokine storm, what do you see in a patient in the midst of one of these immune reactions? Does this account for the arcing nosebleeds and vomiting?

]]> By: Jackson Harding http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26607 Jackson Harding Thu, 14 May 2009 12:40:45 +0000 http://www.crikey.com.au/?p=58340#comment-26607 This one also deals with cytokine storm http://www.ncbi.nlm.nih.gov/pubmed/19218453?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_PMC&linkpos=2&log$=citedinpmcarticles&logdbfrom=pubmed (although it's in non-human primates) Jackson This one also deals with cytokine storm http://www.ncbi.nlm.nih.gov/pubmed/19218453?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_PMC&linkpos=2&log$=citedinpmcarticles&logdbfrom=pubmed (although it’s in non-human primates)

Jackson

]]> By: Jackson Harding http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26606 Jackson Harding Thu, 14 May 2009 12:38:26 +0000 http://www.crikey.com.au/?p=58340#comment-26606 Mike, It's not quite as simple as it seems, Morens' paper has reviewed histopathological samples and shown that the damage is the same as that seen in bacterial infection. While bacteria were seen they is no proof that they are the cause of the problem. The haemorrhagic pneumonitis that was seen in 1918-19 is not typical of bacterial infection, the rapid progression to lung haemorrhage is something that appears to be something that only occurs in some strains of influenza (other illnesses also cause cytokine storms, notably malaria, measles and some cases of HIV). Morens et al don't even mention cytokine storm, something I find odd. They also fail to consider the very likely possibility that cytokine storm causes severe lung damage predisposing to massive bacterial overgrowth. This link http://www.ncbi.nlm.nih.gov/pubmed/18697437?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed discusses the role of cytokines and makes the point that the histological changes are similar to those seen in severe infection. This is to be expected, after all these are the chemicals the body uses in fighting infection, they cause inflammation and it's not surprising that the collateral damage they cause is found in both cases. Unfortunately I can only access the abstract, the original article is in a Bulgarian journal and in Turkish, the Western European medical orthodoxy tend to shun these journals and pay them scant regard, often for no good reason. A better journal (Chest, the leading pumonology and critical care journal) has also published this one: http://www.ncbi.nlm.nih.gov/pubmed/16424427?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum It deals mostly with H5N1 infections but presumably H1N1 produces a similar result. Then there remains the issue of why did the 1918-19 strain kill young adults in such unusually high numbers. Cytokine storm still seems to be the likely root cause, the havoc it causes allowing the massive bacterial overgrowth, and then the demise of the patient. This leads to 2 further problems. Firstly antibiotics are good, but they are not magic bullets and not all patients respond. Then from the logistic point of view I see many patients with severe bacterial pneumonia, it is a common cause for admission to ICU. You need the advanced respiratory support while the antibiotics work and your body recovers. There just aren't that many ICU beds, and other demands on them (such as road trauma and other severe illnesses) won't go away during a pandemic. Jackson Mike,
It’s not quite as simple as it seems, Morens’ paper has reviewed histopathological samples and shown that the damage is the same as that seen in bacterial infection. While bacteria were seen they is no proof that they are the cause of the problem. The haemorrhagic pneumonitis that was seen in 1918-19 is not typical of bacterial infection, the rapid progression to lung haemorrhage is something that appears to be something that only occurs in some strains of influenza (other illnesses also cause cytokine storms, notably malaria, measles and some cases of HIV). Morens et al don’t even mention cytokine storm, something I find odd. They also fail to consider the very likely possibility that cytokine storm causes severe lung damage predisposing to massive bacterial overgrowth.

This link http://www.ncbi.nlm.nih.gov/pubmed/18697437?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed discusses the role of cytokines and makes the point that the histological changes are similar to those seen in severe infection. This is to be expected, after all these are the chemicals the body uses in fighting infection, they cause inflammation and it’s not surprising that the collateral damage they cause is found in both cases. Unfortunately I can only access the abstract, the original article is in a Bulgarian journal and in Turkish, the Western European medical orthodoxy tend to shun these journals and pay them scant regard, often for no good reason. A better journal (Chest, the leading pumonology and critical care journal) has also published this one: http://www.ncbi.nlm.nih.gov/pubmed/16424427?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum It deals mostly with H5N1 infections but presumably H1N1 produces a similar result.

Then there remains the issue of why did the 1918-19 strain kill young adults in such unusually high numbers. Cytokine storm still seems to be the likely root cause, the havoc it causes allowing the massive bacterial overgrowth, and then the demise of the patient. This leads to 2 further problems. Firstly antibiotics are good, but they are not magic bullets and not all patients respond. Then from the logistic point of view I see many patients with severe bacterial pneumonia, it is a common cause for admission to ICU. You need the advanced respiratory support while the antibiotics work and your body recovers. There just aren’t that many ICU beds, and other demands on them (such as road trauma and other severe illnesses) won’t go away during a pandemic.

Jackson

]]> By: MIKESTUCHBERY http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26575 MIKESTUCHBERY Thu, 14 May 2009 06:39:39 +0000 http://www.crikey.com.au/?p=58340#comment-26575 Jackson, <a href="http://www.journals.uchicago.edu/doi/pdf/10.1086/591708" rel="nofollow">here</a> is my source - 'Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness'. I would be very interested to hear if there's been a study or a journal article published that sheds new light on the predominant cause of death for victims in 1918. Jackson, here is my source - ‘Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness’. I would be very interested to hear if there’s been a study or a journal article published that sheds new light on the predominant cause of death for victims in 1918.

]]> By: MIKESTUCHBERY http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26573 MIKESTUCHBERY Thu, 14 May 2009 06:27:20 +0000 http://www.crikey.com.au/?p=58340#comment-26573 Has it been verified that cytokine storms have been identified as the culprit, rather than merely <i>suggested</i>? I've seen it discussed in rather hysterical terms in some other articles I've read, prior to researching this piece. Perhaps that is what makes a more lethal flu pandemic a much deadlier prospect- deaths are not due to a singular factor, but a number of reactions or opportunistic infections? Has it been verified that cytokine storms have been identified as the culprit, rather than merely suggested? I’ve seen it discussed in rather hysterical terms in some other articles I’ve read, prior to researching this piece.

Perhaps that is what makes a more lethal flu pandemic a much deadlier prospect- deaths are not due to a singular factor, but a number of reactions or opportunistic infections?

]]> By: Dominitus http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26571 Dominitus Thu, 14 May 2009 06:18:12 +0000 http://www.crikey.com.au/?p=58340#comment-26571 Reading this article made me join Crikey. Very well-written, interesting and engaging. Really enjoyed it, thank you Mr. Stuchbery! Reading this article made me join Crikey. Very well-written, interesting and engaging. Really enjoyed it, thank you Mr. Stuchbery!

]]> By: Jackson Harding http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26570 Jackson Harding Thu, 14 May 2009 06:16:24 +0000 http://www.crikey.com.au/?p=58340#comment-26570 A nice article, ruined by a rather critical factual error. The 1918 flu killed young healthy adults not by secondary bacterial infection, but by a thing called "cytokine storm". Cytokines are the shock troops of your immune system, they are designed to kill invaders. Unfortunately pandemic flus often provoke such a strong immune response that the rest of the body gets caught in the crossfire. The immune response is so brutal that it kills the host as well as the invader (this is not the same as auto immune disease where the immune system turns on the body, this is just the body over-reacting, literally to death). The old and the young don't get to experience the joys of a cytokine storm, their weaker immune systems aren't up to the task of self immolation. Plain old bacteria still get to knock them off. So what I hear you say. Well we have lots of high tech (and some not so high tech) antibiotics to help kill bacteria and treat secondary bacterial infections but we have very little that will damp down a cytokine storm (there are a few things, but no magic bullet and effectiveness is unclear). If this happens to you all doctors can do is admit you to intensive care (and that is a very very finite resource) and hope your body can ride out the storm. If (and that's a very big if) on a second or third iteration this flu causes this sort of response things might get very interesting. Jackson (a doctor, not a hack) PS H1N1 is only one of several "regular strains" that are circulating at any time, and at the moment both the regular or garden variety as well as "Novel H1N1" are out and about. A nice article, ruined by a rather critical factual error.

The 1918 flu killed young healthy adults not by secondary bacterial infection, but by a thing called “cytokine storm”. Cytokines are the shock troops of your immune system, they are designed to kill invaders. Unfortunately pandemic flus often provoke such a strong immune response that the rest of the body gets caught in the crossfire. The immune response is so brutal that it kills the host as well as the invader (this is not the same as auto immune disease where the immune system turns on the body, this is just the body over-reacting, literally to death). The old and the young don’t get to experience the joys of a cytokine storm, their weaker immune systems aren’t up to the task of self immolation. Plain old bacteria still get to knock them off.

So what I hear you say. Well we have lots of high tech (and some not so high tech) antibiotics to help kill bacteria and treat secondary bacterial infections but we have very little that will damp down a cytokine storm (there are a few things, but no magic bullet and effectiveness is unclear). If this happens to you all doctors can do is admit you to intensive care (and that is a very very finite resource) and hope your body can ride out the storm.

If (and that’s a very big if) on a second or third iteration this flu causes this sort of response things might get very interesting.

Jackson
(a doctor, not a hack)

PS H1N1 is only one of several “regular strains” that are circulating at any time, and at the moment both the regular or garden variety as well as “Novel H1N1” are out and about.

]]> By: yakboy http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26567 yakboy Thu, 14 May 2009 05:58:20 +0000 http://www.crikey.com.au/?p=58340#comment-26567 Hack? Look out, he's got the swine flu! Hack?

Look out, he’s got the swine flu!

]]> By: MIKESTUCHBERY http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26566 MIKESTUCHBERY Thu, 14 May 2009 05:50:59 +0000 http://www.crikey.com.au/?p=58340#comment-26566 Goddamit man, virii sounds more sinister. I'm a hack, not a doctor! Goddamit man, virii sounds more sinister. I’m a hack, not a doctor!

]]> By: yakboy http://www.crikey.com.au/2009/05/14/lessons-in-history-what-we-can-learn-from-the-spanish-flu/#comment-26561 yakboy Thu, 14 May 2009 05:20:44 +0000 http://www.crikey.com.au/?p=58340#comment-26561 The plural of virus is viruses! Also, whilst it is true that the flu is an airborne pathogen that can be picked up through inhalation, many scientists believe that this is not the most common method of transmission. Touching surfaces that have had the virus deposited on them, and then touching one's mouth, eyes or other mucous membranes, or one's food, is considered by many to be the greatest risk. So, a person with the flu covers their mouth when coughing, to avoid spreading it, but then touches the handrail on the train, and manages to potentially spread the disease further than if they had just coughed openly. The good news is that good personal hygiene and avoiding touching your face, can help to keep you healthy. Keep that in mind in case of a pandemic! The plural of virus is viruses!

Also, whilst it is true that the flu is an airborne pathogen that can be picked up through inhalation, many scientists believe that this is not the most common method of transmission. Touching surfaces that have had the virus deposited on them, and then touching one’s mouth, eyes or other mucous membranes, or one’s food, is considered by many to be the greatest risk.

So, a person with the flu covers their mouth when coughing, to avoid spreading it, but then touches the handrail on the train, and manages to potentially spread the disease further than if they had just coughed openly.

The good news is that good personal hygiene and avoiding touching your face, can help to keep you healthy. Keep that in mind in case of a pandemic!

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