Acetaminophen   Fever

Paracetamol should not be used for infectious fevers - revisited

Hilary Butler - Saturday, July 30, 2011

This was first published on November 15, 2010.  I've uploaded the medical articles and embedded them, and updated it.  This updation is inspired by the wet-behind-the-ears July 2011 announcement from Wellington experts, that paracetamol shouldn't be used in the treatment of fever during influenza, as well as the ignorance displayed on the Sunday's facebook page..  Why do the Wellington experts only discuss "influenza"?  Have they not read the decades of medical literature which shows this applies to NOT ONLY all infections, but after vaccines as well?  There is also a whole raft of medical articles I have on the use of paracetamol in pregnancy and childhood infections and it's active role in the development of asthma and allergies. 

Over a decade ago, Auckland AUT invited me to talk about vaccines at a day seminar.  I didn't end up doing that, because I was so disgusted at the nurse's presentation, prior to mine. about how wonderful paracetamol was, and how it could be used safely for just about everything, that come my turn, I stepped up to the white board and detailed the medical literature showing the opposite.  If looks could have killed, I would have been dead before I had started.  I was, and continue to be seriously disturbed at the INABILITY of nurses and doctors to do the research required, to understand these crucial, fundamental issues. Instead, when we parents call them on it, they ask US... for proof.  The articles embedded here, are a fraction of the total proof that exists.  So any nurses and doctors directed to this blog, download the medical articles provided here. This should be sufficient for you to then do a much more thorough pubmed search and google scholar search, and download a huge comprehensive database. 

Then ask yourself the question, "WHY wasn't I taught this?" 

And also ask yourself whether or not your "service" to "clients" has been safe.  After all, your primary responsibility is to "first do no harm". Ignorance is no excuse.  And please stop making derogatory comments about those of us, who do actually possess, and know the medical literature, on many more topics that you appear to have even a fundamental grasp of.

To me, it makes perfect sense that if you hamper the innate immune systems ability to function on a broad front, regularly, there will be a price to pay. People ignore the benefits of fever at their peril. See also Skitski.  People should realise that normal therapeutic doses of paracetamol can cause liver damage, and that the use of paracetamol accounts for over 400 liver transplants a year in the USA. Furthermore, there are serious questions being raised about it, given that 65% of pregnant women use paracetamol regularly. 

The mechanism of fever is pretty clear. For a start,  PGT2 is crucial in making sure a fever is effective, and paracetamol shuts off PGT2.  The very mechanism which deals with pathogens is suppressed by paracetamol. the pathways that paracetamol suppresses are diverse.  That fever improves survival from disease has been in the medical literature since 1976.  It's also important to know why infection causes the body to sleep and why sleep is so important.  Blatteis also addressed this in 2003, so it's not a new issue.

NOV 15, 2010:  Today, we are told that fever is good for you! Now where might you have heard that before? Oh yeah. Here of course. And you'll find a chapter called "Fever Pitch" in the book we wrote in 2006. And then there's the chapter called "Bringing chickenpox to the boil" in our second book, published in 2008, which detailed some of the dramas created by Pfizer in 2004, who didn't like IAS and myself telling the nasty little truth about their darling little product called PAMOL. ... about how using it during infections had the potential to kill.  The question is, does the New Zealand team responsible for this article, deserve a bouquet, or brickbats? After all, there's a lot of people who have felt that they have been hitting their heads against a brick wall about the use of Paracetamol in pregnancy, and for infectious fevers, for a very long time.

With the decades of medical literature on fever and antipyretics, this argument should have been dead and buried thirty years ago.

And if not then, at least they could have buried it when the WHO wrote an advisory nearly ten years ago, stating that using acetaminophen during infections was dangerous and unwarranted.

For those who don't know the 2004 Pfizer saga, here's a sequence of documents for you to read:

First Letter from Pfizer to IAS. Second letter from Pfizer to IAS, which expanded on the complaint to include accurate detailed fully referenced information I'd written, which necessitated me helping to draft a reply. This is IAS's very detailed reply which describes the literature I have in great detail. Here is Pfizer's reply to IAS's reply. And in case you're wondering about the fact that Michael Baker authored the press release, about an article he wrote..., here is Michael Baker's article.

In my opinion, I have never misrepresented what was in that article and you can read it yourself, and you be the judge. Furthermore, there is plenty in the medical literature to show that not only does paracetamol increase the duration of the flu, and the likelihood of dying, it does the same for when it comes to ALL infections INCLUDING meningitis.

Here for the record is another email I wrote in 2009, to some medical "bigwigs" attempting to get someone to look at the issues surrounding anti-febriles:

From: Hilary Butler [mailto:butler@watchdog.net.nz]
Sent: Tuesday, 3 November 2009 9:09 PM
To: 'prymula@pmfhk.cz'; 'rtc1@cdc.gov'; 'editorial@lancet.com'; 'richard.horton@lancet.com'; 'astrid.james@lancet.com'; 'ideditorial@lancet.com'
Subject: Vaccines and paracetamol, Lancet October 17, 2009.

Dear Dr Chen and Dr Prymula,

(I have copied in the editors of the Lancet, and the Lancet Infectious Diseases, because to me, this is, and has been, a very important issue, and it is time it was dealt with properly.)

Dr Chen: Your article in the 17 October 2009 Lancet says that the findings of Prymula that paracetamol significantly reduces the antibodies formed after some vaccines given to children, are surprising, and that he’s the first to examine the issue. Yes in humans, but not in animals or in a broader context.

Please find attached Ryan et al, 2006 (labelled HPV vax paracetamol) in which it was shown that paracetamol suppresses antibodies from Gardasil in mice. Please also find attached Yamaura et al 2002 (labelled p supp antib mice) which shows that the effect of paracetamol extends to mitogens as well as antibody suppression.

Please find Australian Prescriber in which Dr Shand discusses the effect of paracetamol on disease, and Shalabi’s two articles explaining how paracetamol down regulates the immune system in terms of disease.

Please find attached the WHO bulletins which comment on how paracetamol increases disease severity and death, and should not be used during infection.

Please access for yourself Plaisance 2000 ARCH INTERN MED/VOL 160, FEB 28, 2000 et al, discussing how the use of paracetamol with influenza increases the duration of the disease in humans by several days: clearly a function of immune suppression. I have attached a news media article about Plaisance 2000 Pharmacotherapy about the same topic (Which also begs the question as to why paracetamol is STILL routinely prescribed for the flu, particularly those for whom a longer duration could lead to serious complications).

The medical literature for over a decade now, has clearly described paracetamol as a potential immune suppressant, and it is probably this action which is behind the association between the use of paracetamol and the subsequently much greater risk of some babies getting asthma later in life. Paracetamol may suppress the way “tolerance” for normal antigens is developed in the neonate, in a similar way to derailing the immune system during infection and at vaccination times.

It is a surprise (to me) that paracetamol has not been banned for use where there is an infection, because of it’s known effects on the immune system. If you were sick with the swine flu and had asthma or other conditions which could place you at risk, wouldn’t you want your immune system to work as well as possible??!  Knowing that paracetamol derails the immune system, would you be happy if you knew (that your doctor didn’t know that) paracetamol might increase the severity of the flu and also your chances of dying? Why is paracetamol always the first line medication for infections and the flu?

You talk about paracetamol’s importance in relation to other vaccines. Given that vaccines can interact, and antibody levels can drop for some diseases, when combined with other multiple vaccines, without paracetamol, it would seem that there are two issues intertwined issues here. The already known effects of paracetamol on the adaptive immune system in BOTH disease and vaccines, and the known interaction of vaccines, which can also drop antibodies. Both are separate, but relevant. As you add more vaccines, even without paracetamol, interactions can cause the same effect.

Dr Prymula: While you are the first to look at this issue in humans (Dr Chen, why did it take so long?) I was surprised that your paper did not contain any of the papers I have attached, since they add considerably to the immunological rationale.

In the light of Shalabi’s 92 and 96 articles and others medical literature proving that paracetamol has a fundamental effect on the immune system (there are several older papers which show that the use of paracetamol in bacterial infections and meningitis, increases severity and mortality), and that paracetamol suppresses antibodies in mice… and after Gardasil, can either of you explain to me why paracetamol’s affect on the immune system came as a surprise to you, and why it is that you appear to be hesitant to describe the research on the mechanisms already uncovered?

I realise that that might broaden the issue out more to include infections as well, but perhaps it’s time for that to be done.

Sincerely,

Hilary Butler.

Dr Chen's reply was:

From: Chen, Robert (Bob) (CDC/CCID/NCHHSTP) [mailto:rtc1@CDC.GOV]
Sent: Wednesday, 4 November 2009 9:11 AM
To: Hilary Butler; prymula@pmfhk.cz; editorial@lancet.com; richard.horton@lancet.com; astrid.james@lancet.com; ideditorial@lancet.com
Subject: RE: Vaccines and paracetamol, Lancet October 17, 2009.

Dear Ms. Butler,

Thank you for your email bringing this literature to my attention. Unfortunately results in animals are not always predictive of results in humans. Our commentary explained "why it took so long". A previous study of acetaminophen with whole cell pertussis vaccine showed there was no impact. So it was assumed that the same would be true of acellular pertussis (and other) vaccines. This may seem obvious in hindsight, but given limited resources, one has to prioritize which wheels you choose to reinvent given slight changes in understanding.

I suggest you make the case for your hypothesis on paracetamol's impact on the immune system in a peer reviewed journal.

Best regards,

My reply was:

From: Hilary Butler [mailto:butler@watchdog.net.nz]
Sent: Wednesday, 4 November 2009 5:02 PM
To: 'Chen, Robert (Bob) (CDC/CCID/NCHHSTP)'; 'richard.horton@lancet.com'; 'ideditorial@lancet.com'; 'prymula@pmfhk.cz'; 'editorial@lancet.com'; 'astrid.james@lancet.com'
Subject: RE: Vaccines and paracetamol, Lancet October 17, 2009.

Dear Dr Chen,

 

Thank you for taking the time to reply to me. Your effort is much appreciated. My reply will perhaps read strongly and passionately. Please do not take this as a personal criticism of you.

Unfortunately results in animals are not always predictive of results in humans. Our commentary explained "why it took so long".

Certainly, animals are not predictive of humans. Vaccines and drugs are first of all tested on animal models, because there is a reason for that. Why, when it suits, does the rationale change? Why are findings seemingly dismissed as “not being relevant in this case”, because it is in ‘animals’? Even if animal tests are clear, “it” could be devastating in humans. Absence of human evidence is no reason to not ask the obvious questions from animal studies… After all, it may be that the wrong questions have been asked. Existence of animal evidence is reason to pursue it further.

America was largely spared the devastation of thalidomide because of the “gut instinct” of the then female head of FDA, who refused to licence it, in the absence of an animal model. At the time, everyone else was scathing of her refusal.

Why is it such a novel concept to also ask the questions, “What is the purpose of fever? If a drug reduces a fever, how does it affect the functioning of the immune system in the broader picture?” Then when that is known, the questions needing to be asked are, “ Is that actually a good idea? What could be the consequences to the person by doing that? If fever gives an adaptive advantage to the bacteria’s host, to help fight the bacteria (or whatever) why would you want to take away a “trump card” like that?”

Same with adults and influenza.

The possible immunosuppressive potential of paracetamol is clearly shown in a stack of medical literature going back 30+ years which addresses these issues, and it’s not unraveling the human genome. It’s ‘inate’ immunological logics 101.

A previous study of acetaminophen with whole cell pertussis vaccine showed there was no impact. So it was assumed that the same would be true of acellular pertussis (and other) vaccines.

Making assumptions which blind the generic ‘you’ to the immunologically obvious, is a constant issue in medicine.

Had the literature I attached to you, been read at the time, wouldn’t the “obvious” questions have simply leapt off the paper at you? If not, why not?

This may seem obvious in hindsight, but given limited resources, one has to prioritize which wheels you choose to reinvent given slight changes in understanding.

Reinvent? Slight changes of understanding? This makes no sense, because Shalabi had elucidated the mechanisms others had similarly discussed …., and those articles should have sent warning bells through everyone’s heads. The changes in understanding are major, with reverberations in all directions.

Most doctors today, still shrug and hold to the old idea that paracetamol is benign, safe, and that fever must be extinguished at all costs. You ask them why, and they blink at you like rabbits in headlights.

You said this was the “first” time this was done in humans, but with the vaccine schedule being so different, that’s not “reinventing”. And without a “first time” in humans, wouldn’t you still be dismissing the evidence because it was animal based, and therefore possibly not relevant? You know that in this case, what applies to the animals applies to humans.

Perhaps the important word in your answer is the word “assumption”:

I suggest you make the case for your hypothesis on paracetamol's impact on the immune system in a peer reviewed journal.

I have tried to make a case for the immunosuppressive impact of paracetamol in peer reviewed journals for many years. I wonder if it gets past the receptionist’s desk actually.

I am a mother, Dr Chen. Publication of mother’s thoughts appear to be hampered by editors who look first, at a person’s qualifications and standing, and whether or not the hypothesis purveyed by a mere mother, might support the status quo, particular relating to various brands of golden geese, which lay multi-million-dollar golden eggs. (And if it did say the same as all the experts, why bother? If it doesn’t, then which medical school did she go to?)

I am reminded of Pillemer and others who have been treated in similar fashion. Medical history has legions of qualified people who have been ignored, or pilloried. And they had more letters after their name than I have. What hope do you think a mother has of being listened to on an issue as important as this? Perhaps someone like Dr Robert Good had the esteem and reputation to get away with thinking out loud. Not so a mere trenchwoman.

More importantly, I fail to see why presenting you with substantive medical literature suggests to you a hypothesis. There’s enough in the 30+ years of acetaminophen medical literature to show any thinking person, that consequent immunosuppression on a broad front, is a bio-immunological reality that is not desirable.

If WHO says (in a mild way) that paracetamol or any related type of drug, should never be used for fever, because it suppresses the immune system; masks serious disease and if you put those two things together, you can have a recipe for disaster, why do you think paracetamol’s effect on the immune system in either infection, or relating to vaccination, is a hypothesis?

Why does it need me to re-collate and present, yet again, that same “wheel” which WHO and others have discussed in the medical literature for some time, to a medical journal, ….. about something which is as immunologically obvious as the nose on your face?

This is something that bugs me when I read medical literature on any specific topic. I have to wade through thousands of pages whereby people repeat all that went before, every single time, just to get to the “new speck of sand”… so if you feel the same, then it’s little wonder, if you didn’t have the incentive to read the literature I sent you.

Banging my head on the brick wall again, isn’t my idea of useful time allocation. That’s why I’m trying the open letter this time. If I try to “talk” to all of you, will THAT make any difference? If not, I won’t die wondering.

Besides which, “you” would want to prove whether or not paracetamol is actually as dangerous as your own literature infers, right? Can you ever see a day when large scale, proper studies are designed on the “assumption” that paracetamol is highly dangerous when it comes to both infection, and to a lesser degree, vaccines, with a possible end point that perhaps paracetamol should NEVER be used during any infectious disease processes of any sort?

Who would provide the funding for something which could be the author of the commercial suicide for a whole class of very profitable drugs, routinely handed out by most medical doctors in hospital and private practice, and are exceedingly profitable, OTC?

There is a joke in this country that while a dog is a man’s best friend, pamol is a mother’s best friend. I am horrified at how often and for what reasons, mothers use paracetamol products. Parents should be told why they should not use paracetamol during infections, or to use it to quieten a whinging child etc. The current usage as primary child manager is drug abuse.

Moving on to adults, how many liver transplants are required every year due to damage done by paracetamol? It’s a phenomenal number. Why are adults totally ignorant of the dangers of paracetamol? Why do adults automatically pop in a paracetamol at the first sign of fever, or the pain of the flu? Because that’s what doctors tell them to do. Because doctors no longer know any other way to deal with it. Besides, to explain the old ways takes time and effort, but writing out a prescription comes at the click of a mouse.

Doctors should be at the forefront of a move to stop this (ab)use of paracetamol, by every day, thumping their fists on the table and saying, “For the sake of our children, adults and future generations, this drug abuse has to stop”.

It’s no good mothers being expected to “convince” doctors.

What I hear, is resounding silence. It’s not good enough.

Regards,

Hilary.

I got no reply to that one, nor did I expect one.

But here's the real deal, and it's not a conspiracy. It's simply a commercial reality.

The REASON nothing was done about this up until now, was because medical KOPS (Key Opinion People)  or KOLS as they are sometimes called (Key Opinion Leaders) were right in the back pocket of the pharmaceutical companies when it came to anti-febriles.

Some still are. And guess what? The proof of that, is in a medical article from some time back, which is quoted from, in the letter to Pfizer.

And on that note, WHY did Pfizer chose to attack IAS on the comments made? You have to wonder if Pfizer actually ... didn't know ... the depth of information in the medical literature about just how dangerous acetaminophen is during infections. Because after it was presented to them, while there was a bit more legal bluster, they basically ran a mile.

PS I had a third party instigate Advertising Standards procedings against Pfizer for multiple breaches of the Act.  Not only did that go nowhere, because the MOH said they were "happy" with Pfizer's blatant breaches of the Act, but Pfizer promptly foisted PAMOL off onto Johnson and Johnson.

Who continue the non-information to this day.