For the first time in medical history we may be seeing an influenza pandemic unfold in real time, but that doesn't mean we know what we are seeing. There remains some uncertainty about virulence, both in terms of how often it kills and how it kills when it does kill. You'd think both would be easy to determine, but those who have been following along know the problem of how often infection with this virus kills is made almost impossible by not knowing how many people it is infecting. But what about the question of how it kills? There are mainly three scenarios of interest: primary viral pneumonia (the flu virus destroys the deep lung tissue on its own); primary viral pneumonia superimposed by a secondary bacterial infection; death by secondary bacterial invaders with the damage from the flu virus playing little part. In seasonal flu and previous pandemics bacterial infection has played a prominent part in the immediate cause of death. Two small series reporting clinical details of severe cases have been previously reported, 30 hospitalized cases from California and subsequently 10 critical care patients in Michigan. Neither showed evidence of bacterial co-infection. If this virus is acting differently we need to know it.
So what's the problem? Don't we have the bodies? Yes and no. First we don't always know which deaths are flu deaths, for reasons we've detailed here many times (here's one such post). Only a small fraction of deaths are autopsied in the US and death registration and handling are done at the state level. CDC has asked medical examiners and local and state health departments to submit tissue samples from post mortem lung specimens and has just reported on the results from 77 confirmed, but still not representative, fatalities in the May 1 - August 20, 2009 time period. Eight states provided all the cases: California, Hawaii, Illinois, New Jersey, New York, Texas, Utah, and Virginia. What the report showed is different from the results of the two early series and more like what is characteristic of previous pandemics. Bacterial co-infections may be playing a major part in fatalities:
Evidence of concurrent bacterial infection was found in specimens from 22 (29%) of the 77 patients, including 10 caused by Streptococcus pneumoniae (pneumococcus). Duration of illness was available for 17 of the 22 patients; median duration was 6 days (range: 1--25 days). Fourteen of 18 patients for whom information was available sought medical care while ill, and eight (44%) were hospitalized. These findings confirm that bacterial lung infections are occurring among patients with fatal cases of 2009 pandemic influenza A (H1N1) and underscore both the importance of pneumococcal vaccination for persons at increased risk for pneumococcal pneumonia and the need for early recognition of bacterial pneumonia in persons with influenza. (MMWR, CDC)
We learn from this report that only slightly more than half (41) of these lab confirmed fatal cases were diagnosed as swine flu H1N1 before death. Only three quarters had even partial clinical information, so for a quarter of these fatal cases we don't know much else except they died after being infected with influenza virus. Less than half had preliminary autopsy reports submitted with the clinical specimens. Already you can see that some essential information is missing, even when sections of lung tissue from confirmed cases are available. It is quite possible that some tissue that would show bacterial infection was not included in the sample. It's hard to be sure this didn't occur and CDC acknowledges this. The tissue that was submitted was then subjected to a prescribed battery of special tests specially sensitive to detect a handful of bacteria often found in influenza. But CDC also admits that some tissues may have bacterial infections they didn't test for. The tissue were examined microscopically and then using special assays for S. pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, or Haemophilus influenzae.
As noted, 22 of the 77 cases had evidence of coinfection with one of those four bacteria, most frequently (10 caes) with S. pneumoniae, the organism that the pneumovax vaccine for pneumococcal pneumonia is directed against. The others: six with S. pyogenes, seven with S. aureus, two with Streptococcus mitis, and one with H. influenzae; four cases involved multiple pathogens. Median age of the fatal caes was only 31, the youngest 2 years, the oldest 56. With non pandemic flu, 90% of the fatalities are over age 65. This epidemiology is dramatically different. They were split 50 - 50 male/female.
There was much information unavailable that would have been interesting to know. For example, we only know if medical care was sought for 18 of the 77 patients. It was for 14, meaning that 4 patients died without ever having had any medical care. In my view says something about our health care system, but I have no doubt some of you will blame the victim. We just don't know and the question is important. Half were sick for 6 days or more, the range being from 1 day to 25 days. So more than half died within a week of illness onset. Of the hospitalized patients, all required ventilators, which isn't surprising. These were fatally sick people. And of the nine patients for whom information was available, 7 got antibiotics for bacterial infection. So these were people who were treated in intensive care units with modern mechanical ventilation and today's arsenal of antibiotics and they died anyway. If you think that we don't have to worry about influenza because we now have modern intensive care units and antibiotics not available in 1918, give this some thought.
These new data, while not representative of all deaths, are giving a different picture than the earlier reports where surprisingly no bacterial co-infections were being found. What's the explanation? However this might be related to the difficulty in establishing that bacterial infections are involved, which are not detected in many routine tests. CDC reports that less than 10% of patients with clinically diagnosed pneumonia have positive blood cultures. And even with lung tissue, sophisticated methods like PCR and immunohistochemistry has been found to detect infections missed by the usual methods, even after death. When the newer methods are used, as here by CDC, evidence of bacterial infection is being found.
It's worth emphasizing again that the most common bacterial infection (10/22) was S. pneumoniae, the cause of pneumococcal pneumonia, for which there is a vaccine available (pneumovax). No data was available on whether any of the 22 fatalities had gotten a pneumococcal vaccine, but CDC determined that 16 of the 22 were in categories CDC recommends be vaccinated with pneumococcal vaccine. We have previously discussed this and it is our opinion it is a wise move for anyone over the age of 2. There are different vaccines for children and adults so you have to ask your health care provider. But you should ask. CDC still recommends it only for those between 5 and 64 with certain risk factors, but I fail to see the logic of this (it's recommended for all children less than 5 and adults older than 64). But even for the recommended group, probably less than 20% have gotten it. Get it, regardless, is our advice.
Is this good news or bad news? First, it has to be confirmed. It's early news, still. I suppose it could be construed as good news that this isn't acting like a strange flu virus that kills all by itself with a virulent primary viral pneumonia. But the bad news is that it still kills, and that if you are counting on post-1918 antibiotics and computer controlled mechanical ventilators to save your bacon, you better think again.
I confess this item seems more alarmist than is typical for the generally sober analysis on this site. For example, do we know what percentage of seriously ill patients are successfully treated with antibiotics and ventilators? This surely has some bearing on whether or not it is reasonable to think that medical developments since 1918 might not make a significant difference to the mortality rates for this new flu.
Having not commented previously, it is probably churlish to start with a critical comment. So let me add that I appreciate very much the high quality informational content, analysis, and reasoning on this site. Thank you.
Brian: It's a fair comment and I'd answer it this way. There is a great deal "out there" (and the Holland piece I discussed the other day is a typical example) that thinks that because we have modern devices like sophisticated ventilators and antibiotics, neither of which we had in 1918, that the secondary bacterial infections that killed the majority of people then would be no problem today. Not at all true. Flu deaths are ARDS deaths and the mortality from ARDS is still frightfully high. Like sepsis, we still don't know how to cope with it. That was the main point, but this series, not being representative doesn't prove that no one will be saved by modern means, I quite agree.
I'm reading this on the heels of one of the biggest radio hosts in CT spending the morning arguing against mandatory H1N1 vaccinations for health care workers. At least a bunch of his listeners, including patient contact HCWs, disagreed with him. After a lot of that, he followed it by saying that we don't have a pandemic. Sigh.
I am not a flu expert but I believe that a significant factor in death from flu is the host response to infection, not the virus (or bacterial secondary infection) direct action on the lung.
There are promising hints that some drugs and compounds can moderate the host response. (These include statins, fibrates, glitazones, COX-2 inhibitors and other anti-inflamatory agents.)
In addition, there are other compounds that seem to have antiviral activity including chloroquine, resveratrol, catechins, and curcumin.
Since we are faced with a potential pandemic, it would be good to investigate all of these possibilities. Particularly since many of these other drugs and compounds are inexpensive and readily available in most parts of the world.
Mark: We've covered this here for several years. If you use the search bar on this site and search for "statins" you'll get most of our posts, including the ones mentioning rosiglitizone. I'm running for the airport or I'd put the links in here. Unfortunately, if they work we're going to have to find out as we go along as there has been little in the way of trials so far.
I have to say that this:
only slightly more than half (41) of these lab confirmed fatal cases were diagnosed as swine flu H1N1 before death.
isn't very encouraging. Over the summer, I went with my partner to a doctor visit when she was exhibiting fairly classic flu-like symptoms -- fever, sore (strep-like) throat and some coughing, aches, fatigue. They sent her home with the classic "drink lots of fluids" advice, didn't even test for influenza. She recovered fine, but it took about two weeks, wound up including a bad ear infection, and was really nasty. I suspect that she's still recovering in some aspects (about a 7% drop in body weight followed the illness, from which she's only now gaining any back).
Of course, I have no idea whether it was even flu, much less swine flu, but that they didn't even check for it or seem terribly concerned about those symptoms popping up in late June is a bit disconcerting, frankly, and indicates to me that even those with access to doctors can't count on them in all cases to take their illness very seriously until it's very nasty.
Revere it would help your research to pay more attention to countries that have tax revenue and whose ERs function as ERs instead of paying ER costs to treat festered should've-been-cheap-clinic treatment. When bioterror happens EU Canada and I assume China will pay the public costs of protection, USA won`t. We spend 8-10% GDP on healthcare you spend that and 7% extra to insurance parasites. When our costs double will yours increase 9% or will they double too? I'm serious, the rest of the world will protect ourselves and your insurance companies will spend that 2025 respirator budget on insurance exec Bling and debt interest payments. Might as well emmigrate now or at least refocus upon nations that will take any advice you give.
I'm wondering about this, because two children I know (classmates of two of my kids) are being treated for pneumonia right now. Would it make sense to start treating everyone with a serious case of influenza with antibiotics up front?
It would be interesting to know why those people didn't seek medical care. Was it because they were worried about the bill, or couldn't get in? Or was it because they got suddenly very ill and then things went downhill from there? (It's normal when you get sick to wait it out for a couple days, if you're not deathly ill. Maybe for some folks, that's too long--I gather it's too long for Tamiflu or Relenza to help much, right?)
Crosspost from Crofsblog
When a pandemic comes, our courts need surge capacity
An opinion piece in today's Globe and Mail: When a pandemic comes, our courts need surge capacity. Excerpt (but read the whole thing):
In preparing a pandemic bedside triage protocol for H1N1, Hamilton Health Sciences has done what we should all do: hope for the best and prepare for the worst.
This first Canadian protocol is a courageous attempt to set forth who should receive life-saving care if access becomes limited. Yet no matter how thoughtful the protocol, it could become subject to legal challenge at the height of a pandemic. Litigation by loved ones in an attempt to move a patient up the triage hierarchy could prove disastrous if the judiciary is not ready.
Two recent legal cases have shown that the judiciary's response can create serious challenges to hospitals providing intensive care.
In the case of Calgary's Zongwu Jin, in 2007, the family sued to ensure that intensive-care physicians would attempt resuscitation if their father required it. The physician believed it would put Mr. Jin, 66, in a persistent vegetative state. The Calgary court temporarily ruled in favour of the family, so he was kept in an ICU bed for four days, not because he needed it (he was ready for transfer to a less expensive bed) but because the court had granted a temporary order pending a full hearing.
The point isn't that there was disagreement, but that the process of resolving the disagreement created other serious problems. Although four days is a brief time when measured by the ordinary workings of the legal system, hours count in a medical setting that operates around the clock, usually to capacity, even without an epidemic.
The second case, also in 2007, had even more serious effects. It concerned Samuel Golubchuk, an 84-year-old Winnipeg man whose children sued in order to prevent physicians from removing his artificial ventilation and feeding.
Despite a nurse's testimony that Mr. Golubchuk had 45 litres of excess fluid leaking from his body, the judge granted a temporary injunction requiring that Mr. Golubchuk continue to receive intensive care. More to the point, the court took two months to rule on the temporary injunction and scheduled the trial 10 months after the initial application. Mr. Golubchuk died four months before trial. No law was developed to guide future disputes.
These two cases allocated the scarce medical resource of intensive care on legal procedural grounds: Pending a full hearing, the judgments sought to preserve the status quo. But in medicine, âthe status quoâ is an elusive concept. A delayed decision can be an actual decision.
By ruling that Mr. Golubchuk should stay in the ICU for 10 months before a trial could begin, the court was actually deciding on overall management of the unit, and created a situation in which two intensive-care physicians quit. A decision that was ostensibly about one patient had definite, but unreported, effects on many other patients who were not represented in the initial hearing.
September 30, 2009
Revere, I just read this article and the previous one saying one should get the Pneumovax vaccine. I am 39, I have thryoid cancer two years ago, of which I think I am now clean. (but you never know). My PCP said I could get the Pneumovax vaccine of which I have an appt. on Friday. I have to admit, I am afraid I might have a serious reaction to this vaccine. Has it been well tolerated by people? Some of the claims of severe side affects, scared me. Gullian Bar, shock, etc...
When you say that the shots are different for kids, can you explain exactly what that means? My kids are fully vaccinated, including the pneumococcal conjugate shot they got somewhere before the age of 4. Is that the shot for kids you're speaking of, or do they need a different immunization to be protected? (Mine are 6 and 4.)
Here is some interesting data suggesting that keeping your vitamin D level optimal will prevent colds, flu and in particular H1N1 (swine Flu).
Here are links to two interesting articles:
August 2009-Vitamin D3 deficiency and its role in influenza
Sept 2009-More on Vitamin D3 and influenza
If these links donât work go to www.vitaminD3world.com and click on âIn the newsâ to find these updates.
This site also offers a free newsletter and has recently launched a new micro pill formulation of vitamin D.
Curious: Just landed after traveling all day so I can't give complete answer. Go to the CDC website and you'll find the details on the pneumococcal vaccine.
1. Most folks have not got the pneumovax vaccine and are unlikely to get it.
2. Folks with influenza are dying from secondary bacterial infections.
3. The HC system will be overly stretched during a pandemic and inadequate resources available to diagnose in a TIMELY fashion that a secondary bacterial infection has developed and needs treatment.
Given these facts, maybe a prophylactic course of antibiotics to those with influenza should be considered.
But maybe pushing vaccines is more profitable.
Vaccines aren't particularly profitable. Also, we'll pay for more than just antibiotics when secondary infections set in.
What's the old saying? An ounce of prevention is worth a pound of cure?
Guns (modern medicines) don't kill people, people (companies that gloss over the faults of their modern medicines, so they can make huge profits), kill people.
The real unfolding tragedy is that Tamiflu was approved by FDA with a gaping hole in it's defense against Influenza A (bird flu, seasonal flu, swine flu) whenever the H274Y mutation occurs. Using Tamiflu doesn't cause mutation, a percentage of the mutation has always been present in the population, Gilead knew that, Roche knew that, and the FDA knew that but instead of fixing the problem before Tamifu was marketed, it was more important to beat Relenza into the U.S. antiviral market.
Relenza had been tested for almost ten years for resistant strains, resistance was so important Biota chose an inhaled antiviral because it wasn't a compromise. Tamiflu was a "good enough" compromise that was so successful that Relenza factories were shut down, only opened when deadly bird flu became a pandemic threat.
Unfortunately Tamiflu was so profitable that it became a marketing monster, all but destroying Relenza and left no profit for GSK to spend on iv Relenza (iv zanamivir) or LANI Relenza (the first version of laninamivir), both products were being developed in the 1990's and deserved to reach final trials because now i.v.zanamivir is only being used experimentally for compassionate use only and will never be marketed according to GSK, and LANI Relenza is just as good as laninamivir (both Biota products) which could have been available a decade ago.
Tamiflu became such a huge cash cow that the H274Y flaw was ignored by the FDA, CDC, WHO, and all the "health professionals" prepared to take the bribe/funding and ignore the science.
Modern medicine hasn't a hope against voracious greed and hypnotic funding.
Revere, sorry to bug you again. But did you have any reaction to the Pneumovax vaccine? What about other people that you know? It would helpful if you could let me know. Thank you.
Bet: No reaction at all. Just like any other vaccination for me.
My daughter had a secondary infection with S. pneumoniae (after RSV) when she was 3. It was so unbelievably bad. I can't even go into details because it still freaks me out so much (this was over 4 years ago). Because of what I went through, your post makes a lot of sense and I wish the powers that be were pushing Pneumovax as hard as the H1N1 vaccine.
But what I was wondering was: does anyone have an opinion about re-vaccination with Pneumovax? A lot of the literature out there is unclear. My daughter got Pneumovax 4 years ago and has a strong, healthy immune system and no lasting effects from her illness. I concluded that re-vax within 3-5 years is only needed for kids with compromised immune systems (someone who is asplenetic, for instance) and that a re-vax for a healthy kid was at best pointless and at worst harmful, based on the evidence out there. Anyone have an opinion on that? Thank you.
A nurse at my doctor's office flat refused to offer the Streptococcus pneumoniae vaccine to anyone outside of the recommended CDC age categories! What's a health-conscious person to do?
Pete, Did you daughter get Prevnar or Pneumovax at 3? There are guidelines about revaccination Pneumovax, but want to make sure which one she got. IanW, I think you can look at CDC new reccomendations and call your nurse and show her again...
Prevnar at age 2 or 3. Pneumovax at age 4. The guidelines I've read seem to say we should be good for now. Let me know if you read something different. Thank you!
"A nurse at my doctor's office flat refused to offer the Streptococcus pneumoniae vaccine to anyone outside of the recommended CDC age categories! What's a health-conscious person to do?"
Talk to her boss the doc. And if that doesn't work, find a different doc!
The main stream approach to health is completely flawed. Healthy immune systems can tackle the flu easily. Healthy immune systems should be the goal. Instead we attempt to boost immunity to certain diseases with vaccines. Why? It's a profit making scheme. The key to health is in a healthy diet and exercise. The use of drugs and vaccines should be the last resort. It should be a rare event to need a drug or vaccine. The fact that we are trying to vaccinate billions for a mild flu virus proves we are in the dark ages of medicine.
revere: so should we take a vaccine that was rushed to production without the proper scientific testing or should we opt for a natural god-given substance that has shown it helps to fight the exact nature of how this disease spreads?
This really could be Nature's miracle product!!!
Do remember that miracles are non-transferable and non-repeatable. Otherwise they would not be miracles.
Taco, I want to believe that healthy immune systems can tackle the flu easily. but if so, why are young health people with no underlying health conditions dying of the swine flu over and over again? I wish my immune system was enough, but in this case I don't think so. I am on the fence of getting the pneumovax vaccine to protect me. Afraid of a dangerous reaction or long term side effects.
Bet - My son and I had the pneumonia vaccine last week - other than a slightly sore arm for both of us, there was no reaction.
Taco - if you think a healthy immune system is protection from the flu, please research "flu and cytokine storm."
Mark,MD - I agree that host response has to be involved. Every week, healthy young people die from H1N1 while others only get "mildly" ill. There has to be a variable. My son unfortunately is one who gets a severe inflammatory response to respiratory infections. He is also at high risk as an asthmatic and likely to contract it as college student in crowded classrooms. I'd like to lock him in his room but he isn't going for it. What would be optimal care in his situation - anti-virals, antibiotics at the beginning of the flu and something like statins if things go really bad? If he sought care at our local hospital, the best he could hope for would be "take 2 aspirins and call me in the morning". I'm sure the response at first medical contact has a lot to do with the outcomes people have.
I have read info about flu and Vitamin D at http://www.vitamindcouncil.org/ and I find it very confusing. The position there seems to be this: high blood levels of Vitamin D can be protective against the flu but average levels can be worse than very low levels. It seems that high levels may suppress the cytokine response to the flu virus; low levels of Vitamin D can cause deficiences of certain parts of the immune system that take part in the inflammatory response. I have no doubt my son is quite deficient in Vitamin D so which way should he go - no Vitamin D at all, a little, mass quanitites of it? I'm strickly a layman. Maybe one of you more knowledgeable people could help me out here.
Yes, healthy immune systems should have no problems with most disease, but as your health depend on diet, genes and non-dietary environmental causes (e.g. said pathogens), seemingly healthy people may not be healthy. As e.g. indicated by the occurence of low vitamin D, A and zinc in the general population. In both the preceeding examples too little and too much are "bad for you".
Do *not* give aspirin (acetylsalicylic acid) as it may cause Reyes' syndrome and thus increase the risk for both a fatal outcome and secondary bacterial infection. Most of the bacteria that cause pneumonia live in the upper respiratory tract and in your mouth, so they are difficult to avoid. This is a problem in medical care see e.g. http://www.biomedcentral.com/1471-2334/9/104.
The current suggestion for optimal vitamin D levels is 80-100 nmol. You should not give any vitamin D unless you have measured D levels and gotten a medical opinion. A sudden increase of vitamin D levels may cause a temporary suppression of the immune system exacerbating any current infection. Do note that it is commonly the host response (that is: your immune system) to the pathogen that cause tissue destruction, not the pathogen per se. That is why vitamin D may be beneficial by "stopping" the immune system from "going rogue".
Bet: I got the pneumovax vaccine several weeks ago and have suffered no ill affects. I won't get the vaccine but wanted to do something as the lungs are a target for many falling ill with flu. And I cannot as a rule handle 99% of pharmaceuticals so it was a game of chance for me that appears to have worked out.
Is there a looming shortage of the PPSV pneumococcal vaccine? In part because of Revere's post June 7th about why it would be such a good idea to get the vaccine, I decided to line up at work today to get only the PPSV that the health department said it was offering in addition to the seasonal flu shot. I have an appointment with my PCP next week when I hope to get the seasonal flu shot.
The lady dispensing shots did not want to give me the PPSV, even though I had cold, hard cash in hand and I'd never had the shot before. She said I did not fall into any risk categories (I'm age 52, no underlying health conditions other than seasonal allergies). I asked her if she was refusing to vaccinate me. She hedged, then said if I get it now, I can't get it again until I'm 65, implying a huge risk down the road. Give it to me anyway, I said. This won't protect you against swine flu, she insisted. No kidding, I replied, although it may help with a secondary bacterial infection following the viral infection. I argued with her for 15 minutes before with rather bad grace she finally vaccinated me.
What's up with the attitude and reluctance to give the PPSV? I asked around later and discovered that although not many coworkers had requested the PPSV (most were there for the seasonal flu shot), many of those who did ask for it were met with the same resistance. In fact, most of them were talked out of getting the pneumococcal vaccine and just got the flu shot. Why would the health department be acting in this fashion (hell, why advertise that they're offering PPSV shots when they'd apparently much rather not administer them?).
I've got a surprising amount of pain and swelling at the injection site now. I hope I didn't rile the Shot Lady so badly that she went for the joint.
Kim, not sure what's with your health dept woman, but when I phoned my primary doctor's office to asked about the PPSV--I've had one but it's been 5 or 6 years since--I was told I don't need one. I explained re secondary infection should I get the new flu, etc., just got the repeat "It's not necessary." Is this vaccine getting low, or perhaps people tired of doing vaccinations all day every day, or--?
Paula, from what I understand the the PPSV can confer protection for decades. In fact, there may be some bad side effects from re- vaccination unless you have since acquired a disease that makes you immunologically vulnerable. But I'm not a health care provider, just was wondering WTF was going on when average middle-aged folks were being talked out of getting the PPSV vaccine.
My son was diagnosed with H1N1 last Monday. He became ill saturday and I became ill Sunday. They put me on a small dose of tamiflu but not the full dose. The virus has now gone to my lungs and I have a mild viral pneumonia on one side. Today is the 6th day from my symtpoms. I am on full dosage of tamiflu and antibiotics and monitoring from home. The WHO came out yesterday and said people are dying from the Viral Pneumonia on the 5th or 6th day. I have never been so scared in my life. I don't feel terrible, don't think I have shortness of breath, no fever, but are really tired and it hurts when I breathe on one side of my lung. Should I be at the hospital if I am not severely ill at this point? Am I going to go into a sudden downward spiral? Does Tamiflu help if started late like me? Help. What else can I do to help my body rid of this viral pneumonia?
Laura: I don't like to do medicine by long distance but my general philosophy is that it's all in how you feel. If you start to feel really sick then it's time to seek additional check-up, especially as they seem to have you on the right regimen. If you aren't having more trouble than what you described, home is the best and safest place for you..
Thank you Revere. Are there cases of mild pneumonia from swine flu that all of a sudden turns deadly after a week from first symtptoms? What about the fact that my flu part is over and I am just dealing with the pneumonia part of it?