2013-03-18

The Flu, Influenza, Testing, and Treating

The Flu, Influenza, Testing, and Treating

As the 2012-13 influenza epidemic continues its sharp decline, rapidly approaching its disappearance, it seemed timely to review some of the key facts about the influenza germ, about what is flu, the utility of testing for the influenza virus, and the pros and cons of using Tamiflu.

The Influenza Virus v. The Flu
Let's start with some definitions.   As we all know, the vast majority of all infections in childhood are caused by a category of germs called viruses.  In fact, aside from the example of strep throat, ear infection, and urinary tract infections, nearly all the common infections of childhood are viral.

It turns out there are lots of different types of viruses, and that when it comes to infections of the nose, throat, and lungs, they can all cause the same looking disease:  runny nose, sore throat, fever, terrible coughing, achiness, loss of appetite, disrupted sleep, feeling miserable.    This illness goes by a few different names, but most typically is called a cold or a flu.  Often the illness is called a cold if the family thinks it's not such a bad illness, but if people feel it's causing more than the usual misery, it's called a flu.  So the definition of a cold or a flu is not a medical choice, it's really based on the sense the family and child have about how miserable it is making them.

Now, of the many, many types of viruses causing colds and flus, there is one whose name has the word flu in it, and that would be the influenza virus.  Not all flus are from the influenza virus and not all infections with the influenza virus are flus.   If we look at all the colds and flus (of the respiratory tree, not stomach flus), then the influenza virus is responsible for about 1/3 of them every winter.

So the influenza virus is one species of virus that causes colds and flus, but about 2/3 of colds and flus are caused by other viruses than the influenza virus.

The Seasonal Nature of the Influenza Virus
The influenza virus has a striking quality of showing up every fall, burgeoning into an epidemic, then completely vanishing in the spring and summer.   This year the influenza virus had its peak at the end of December and since New Year's Day has been in very rapid and sharp decline.  That means today, if your child has a cold or flu, it is becoming very unlikely that it will be caused by the influenza virus.
http://www.cdc.gov/flu/weekly/


Are there antibiotics for viruses?  What does Tamiflu do?
As many of you know, most antibiotics only kill bacteria.  That's because bacteria are radically different than viruses, and us.  Bacteria are little one-celled organisms with their own special chemistry.  Drugs like penicillin wreak havoc on their special chemistry, but since viruses and us do not use that chemistry, these antibiotics are harmless to us.

That leaves us fairly powerless to treat nearly all viruses, since we have very few drugs that really interfere with their chemistry.

There are a couple of exceptions, a group of drugs that kill viruses, although when it comes to killing viruses, each drug tends to kill only one type of virus.  This is a bit different than antibiotics killing bacteria, where one antibiotic can kill a very wide variety of bacteria of many diverse species.  So there are drugs like Acyclovir that kill herpes but not influenza virus.  And then there is Tamiflu which can halt the infection process of influenza species viruses, but not herpes or other viruses.

Now Tamiflu, or oseltamivir, actually does not kill the influenza virus, at all.  It interferes with one step in its reproduction.  Viruses work by invading our cells, commanding them to make copies, and then spewing out the new viruses to repeat the cycle.   Tamiflu simply keeps the newly created viruses from separating from our cells, they get stuck, and the infection does not continue.

How well does Tamiflu work?
In thinking about how well Tamiflu works, it is good to keep in mind that it can only control infections with one species of virus, the influenza virus.  So if you have a cold from some other virus, Tamiflu will not do anything to help at all.   As of mid-March, 2013, the number of colds caused by the influenza virus has dropped to the point that 95% of all colds and flus are not caused by the influenza virus.

But what if you know your virus is the influenza species of virus?  Tamiflu turns out to be a very weak drug in actual practice.  One of its failings is that if you take after 48 hours of being sick with the influenza virus, you likely will notice no benefit at all.   And, if you take it right at the start of symptoms, on the average, your viral infection will last only 36 hours less.

Now why is the help it offers measured in average numbers less of being ill?  That's because it's impact is so mild that if you take Tamiflu with an influenza viral infection, you will still be sick, and so it's hard to know if it "worked."  To get some measure of if it works, the studies take a bunch of people all infected with influenza virus and give half of them Tamiflu, and half nothing.   All of them get well in a week or two, or less.  And so the effect of Tamiflu is measured in the difference in the average number of hours the treated group is sick compared to the untreated group.  And that difference was 36 hours.

To our minds, that's not a very dramatic impact.  If you get an influenza viral illness, you might be sick for 9 1/2 days without Tamiflu and, on average, 8 days with Tamiflu.

But what about everyone's friend who was treated with Tamiflu and was well the next day?  That happens, but when it does, it is impossible to know if that person was about to get well without the Tamiflu.  That's the value of the studies, we can actually measure how groups fare with and without treatment.   No study has ever demonstrated any pattern towards rapid and complete recovery within a day of taking Tamiflu.  

So the evidence strongly suggests that if you have had the flu from the influenza virus for a week, get so exasperated about being ill that you go to the doctor, get placed on Tamiflu, and are fine the next day; then, you are far more likely to have been on the last day of your illness and destined to feel well the next day, than for your recovery to be so dramatic from use of Tamiflu.

A review of the impact on the health of those infected with influenza in England concluded that the use of Tamiflu may have reduced symptoms by about a day (in line with the 36 hours quoted above), but had no impact on the risk of anything serious happening- including complications and hospital admissions.

What harm can Tamiflu cause?
It turns out that Tamiflu is not harmless.  Lots of people who take it get nausea and even vomit.
More rarely it can damage your liver and cause dangerous heart rhythms.
And, it is becoming clear that taking Tamiflu can have a serious impact on your moods and thinking.
In countries where Tamiflu has become a common drug to use with influenza infections, there has been a rise in dangerous neurological and/or psychiatric reactions.

Should otherwise healthy children who catch a cold or flu, and found to have it by an influenza virus, be treated with Tamiflu?
The answer to this question, as all such questions should be answered, hangs on how well Tamiflu might help and how badly it might hurt.

The consensus across nearly all studies is that Tamiflu doesn't really do much.  It clearly fails to stop the illness to any dramatic degree.  It is useless after 48 hours of being ill.  And even in the best of circumstances, can only be expected to shave a day or so off the illness.  It prevents no complications.  This is a very weak intervention.  So the benefit is quite limited.

On the negative side, there are very serious harms risked in taking it.  Harm to the liver is a very dangerous event, as are dangerous heart arrhythmias.  The prospect of inducing dangerous psychological events, particularly in children, is deeply disturbing.   And for what benefit are these risks being taken- 1 day less of a cold or flu.  

In balance, the choice seems clear that a city's children will be better off without using Tamiflu for routine, uncomplicated infections with the influenza virus, and clearly better off in not using it for other viral infections for which it does even less.

One last point, there is no doubt whatsoever that if we begin to use Tamiflu routinely for childhood influenza viral infections, the virus will develop resistance.  So this practice, which offers so little benefit and very real risk, will in the space of a few years render the drug completely useless.  This is an issue for the rare instance of a very serious infection with an influenza virus where even a very limited bit of help from a drug like Tamiflu could save a life.  Using up the potential of this drug saving a life for rare infections with the influenza virus by letting its use go widespread for fairly mild illness seems like a very dangerous plan.

Testing for influenza virus
When someone has a cold or flu of the respiratory system (nose, throat, lungs) it could be caused by a dozen or so various species of virus.  When should your child get a test to see if it is influenza?  Our recommendation is that such testing is useless in mild, uncomplicated situations.  The only reason to find out if a cold or flu in an otherwise healthy child is due to the influenza virus or not would be to see if Tamiflu might help.  But if we agree that the use of Tamiflu is more likely to cause harm than help, then even if the test showed the infection was from influenza, the right decision most likely would be not to treat, in which case the test led to no change in plan, and would be unhelpful.

Now, there are situations when testing makes sense.  They nearly always involve some degree of complexity-either the child has a serious underlying condition, or the presenting symptoms are dangerously severe.  In either case, the very minimal help offered by Tamiflu might make an important difference, so testing to see if the virus is influenza makes sense.

BOTTOM LINES
  1. Most respiratory colds and flus are not caused by the influenza virus
  2. The influenza virus is here usually from November to April.  It is right now vanishing from the US, until its return at the end of this year.
  3. Tamiflu only has an impact on viral infections caused by the species influenza (not on all colds and flus).
  4. Tamiflu has no or very little impact on your colds or flus if you have been sick for 48 hours or more.
  5. If you take Tamiflu before you have been ill for 48 hours, it has very little impact, at best shaving about 36 hours of illness of your course.
  6. Tamiflu is not harmless.  It can hurt your liver, cause dangerous heart rhythms to appear, and especially for children it can cause serious psychological problems.
  7. Countries and communities that get excited about using Tamiflu for mild colds and flus risk hurrying the emergence of resistant influenza viruses, eliminating the use of Tamiflu for very serious situations.
  8. Tamiflu has a good role to play, with its very limited impact on an influenza infection, when that infection is very severe or in a very unhealthy child.
  9. Putting it all together, we do not recommend the use of Tamiflu in otherwise healthy children with uncomplicated influenza infection, and therefore do not see a purpose in testing for influenza virus in such situations as well

Colds and flus are a source of great trouble and discomfort.  We support the effort to find a cure and to keep them from happening.  Tamiflu is neither.  We are still waiting for the medicine or immunization that will truly reduce the burden from colds and flus.


Dr. Arthur Lavin










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